Infections in early life and childhood leukaemia risk: a UK case-control study of general practitioner records.
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ABSTRACT:
SUBMITTER: Cardwell CR
PROVIDER: S-EPMC2579698 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND: Acute respiratory tract infections (ARTI) are an important public health problem. Improved identification of risk factors might enable targeted intervention. Therefore we carried out a case-control study with the aim of identifying environmental risk factors for ARTI consultations in the Dutch general population. METHODS: A subset of patients visiting their GP in the period of 2000-2003 with an ARTI (cases) and age-matched controls (visiting for other complaints) were included in a case-control study. They were asked to complete a questionnaire about potential risk factors. Conditional logistic regression was used to calculate odds ratio's (OR) and 95% confidence intervals (CI) to estimate the independent effect of potential risk factors. RESULTS: A total of 493 matched pairs of case and control subjects were enrolled. Exposure to persons with respiratory complaints, both inside and outside the household, was found to be an independent risk factor for visiting a GP with an ARTI (respectively ORadj = 1.9 and ORadj = 3.7). Participants exposed to dampness or mould at home (ORadj=0.5) were significantly less likely to visit their GP. In accordance with the general risk of consultations for ARTI, participants with a laboratory-confirmed ARTI who were exposed to persons with respiratory complaints outside the household were also significantly more likely to visit their GP (ORadj=2.5). CONCLUSION: This study confirmed that heterogeneity in the general population as well as in pathogens causing ARTI makes it complicated to detect associations between potential risk factors and respiratory infections. Whereas it may be difficult to intervene on the risk posed by exposure to persons with respiratory complaints, transmission of ARTI in the general population might be reduced by improved hygienic conditions.
| S-EPMC1871593 | biostudies-literature
Project description:Main purpose To evaluate the feasibility of a measurement-based assessment of benzene exposure in case-control studies of paediatric cancer; Additional aims To identify the sources of exposure variability; to assess the performance of two benzene biomarkers; to verify the occurrence of participation bias; to check whether exposures to benzene and to 50 Hz magnetic fields were correlated, and might exert reciprocal confounding effects. Pilot case-control study of childhood leukaemia and exposure to benzene assessed by repeated seasonal weekly measurements in breathing zone air samples and outside the children's dwellings, with concurrent determinations of cotinine, t-t-muconic acid (MA) and sulfo-phenylmercapturic acid (S-PMA) in urine. 108 cases and 194 controls were eligible for inclusion. Full-participation was obtained from 46 cases and 60 controls, with low dropout rates before four repeats (11% and 17%); an additional 23 cases and 80 controls allowed the collection of outdoor air samples only. The average benzene concentration in personal and outdoor air samples was 3 μg/m(3) (SD 1.45) and 2.7 μg/m(3) (SD 1.41), respectively. Personal exposure was strongly influenced by outdoor benzene concentrations, higher in the cold seasons than in warm seasons, and not affected by gender, age, area of residence or caseness. Urinary excretion of S-PMA and personal benzene exposure were well correlated. Outdoor benzene levels were lower among participant controls compared with non-participants, but did not differ between participant and non-participant cases; the direction of the bias was found to depend on the cut-point chosen to distinguish exposed and unexposed. Exposures to benzene and extremely low-frequency magnetic fields were positively correlated. Repeated individual measurements are needed to account for the seasonal variability in benzene exposure, and they have the additional advantage of increasing the study power. Measurement-based assessment of benzene exposure in studies of childhood leukaemia appears feasible, although it is financially and logistically demanding.
| S-EPMC3586103 | biostudies-literature
Project description:BackgroundGenotyping has become more cost-effective and less invasive with the use of buccal cell sampling. However, low or fragmented DNA yields from buccal cells collected using FTA cards often requires additional whole genome amplification to produce sufficient DNA for genotyping. In our case-control study of childhood leukaemia, discordance was found between genotypes derived from blood and whole genome amplified FTA buccal DNA samples. We aimed to develop a user-friendly method to correct for this genotype misclassification, as existing methods were not suitable for use in our study.MethodsDiscordance between the results of blood and buccal-derived DNA was assessed in childhood leukaemia cases who had both blood and FTA buccal samples. A method based on applying misclassification probabilities to measured data and combining results using multiple imputations, was devised to correct for error in the genotypes of control subjects, for whom only buccal samples were available, to minimize bias in the odds ratios in the case-control analysis.ResultsApplication of the correction method to synthetic datasets showed it was effective in producing correct odds ratios from data with known misclassification. Moreover, when applied to each of six bi-allelic loci, correction altered the odds ratios in the logically anticipated manner given the degree and direction of the misclassification revealed by the investigations in cases. The precision of the effect estimates decreased with decreasing size of the misclassification data set.ConclusionsBias arising from differential genotype misclassification can be reduced by correcting results using this method whenever data on concordance of genotyping results with those from a different and probably better DNA source are available.
| S-EPMC3514307 | biostudies-literature
Project description:BackgroundWe conducted a large registry-based study in California to investigate the association between race/ethnicity and childhood leukaemia focusing on two subtypes: acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML).MethodsWe obtained information on 5788 cases and 5788 controls by linking California cancer and birth registries. We evaluated relative risk of childhood leukaemia by race and ethnicity of the child and their parents using conditional logistic regression, with adjustment for potential confounders.ResultsCompared with Whites, Black children had lower risk of ALL (OR=0.54, 95% CI 0.45 to 0.66) as well as children of Black/Asian parents (OR=0.31, 95% CI 0.10 to 0.94). Asian race was associated with increased risk of AML with OR=1.643, 95% CI 1.10 to 2.46 for Asian vs Whites; and OR=1.67, 95% CI 1.04 to 2.70 for Asian/Asian vs White/White. Hispanic ethnicity was associated with increased risk of ALL (OR=1.37, 95% CI 1.22 to 1.52). A gradient in risk of ALL was observed while comparing Hispanic children with both parents Hispanic, one parent Hispanic and non-Hispanic children (p Value for trend <0.0001). The highest risk of ALL was observed for children with a combination of Hispanic ethnicity and White race compared with non-Hispanic whites (OR=1.27, 95% CI 1.12 to 1.44). The lowest risk was observed for non-Hispanic blacks (OR=0.46, 95% CI 0.36 to 0.60). Associations for total childhood leukaemia were similar to ALL.ConclusionsOur results confirm that there are ethnic and racial differences in the incidence of childhood leukaemia. These differences indicate that some genetic and/or environmental/cultural factors are involved in aetiology of childhood leukaemia.
| S-EPMC4550439 | biostudies-literature
Project description:BackgroundStudies have reported an increased risk of childhood leukaemia associated with living near high-voltage electric power transmission lines that extend to distances at which magnetic fields from lines are negligible. We conducted a large records-based case-control study of childhood leukaemia risk in the population living near power lines in California.MethodsThe study included 5788 childhood leukaemia and 3308 central nervous system (CNS) cancer cases (for comparison) born in and diagnosed in California (1986-2008), and matched to population-based controls by age and sex. We geocoded birth address and estimated the distance from residence to transmission lines using geographic information systems, aerial imagery, and, for some residences, site visits.ResultsFor leukaemia, there was a slight excess of cases within 50?m of a transmission line over 200?kV (odds ratio 1.4, 95% confidence interval 0.7-2.7). There was no evidence of increased risk for distances beyond 50?m, for lower-voltage lines, or for CNS cancers.ConclusionsOur findings did not clearly support an increased childhood leukaemia risk associated with close proximity (<50?m) to higher voltage lines, but could be consistent with a small increased risk. Reports of increased risk for distances beyond 50?m were not replicated.
| S-EPMC4931365 | biostudies-literature
Project description:Paternal occupational exposures have been proposed as a risk factor for childhood leukaemia. This study investigates possible associations between paternal occupational exposure and childhood leukaemia in Great Britain.The National Registry of Childhood Tumours provided all cases of childhood leukaemia born and diagnosed in Great Britain between 1962 and 2006. Controls were matched on sex, period of birth and birth registration subdistrict. Fathers' occupations were assigned to 1 or more of 33 exposure groups. Social class was derived from father's occupation at the time of the child's birth.A total of 16 764 cases of childhood leukaemia were ascertained. One exposure group, paternal social contact, was associated with total childhood leukaemia (odds ratio 1.14, 1.05-1.23); this association remained significant when adjusted for social class. The subtypes lymphoid leukaemia (LL) and acute myeloid leukaemia showed increased risk with paternal exposure to social contact before adjustment for social class. Risk of other leukaemias was significantly increased by exposure to electromagnetic fields, persisting after adjustment for social class. For total leukaemia, the risks for exposure to lead and exhaust fumes were significantly <1. Occupationally derived social class was associated with risk of LL, with the risk being increased in the higher social classes.Our results showed some support for a positive association between childhood leukaemia risk and paternal occupation involving social contact. Additionally, LL risk increased with higher paternal occupational social class.
| S-EPMC3493752 | biostudies-other
Project description:Background:Interventions are needed to reduce unnecessary antibiotic prescribing for respiratory tract infections (RTIs). Although community antibiotic prescribing appears to be decreasing in the UK, figures for out-of-hours (OOH) prescribing have substantially increased. Understanding the factors influencing prescribing in OOH and any perceived differences between general practitioner (GP) and nurse prescriber (NP) prescribing habits may enable the development of tailored interventions promoting optimal prescribing in this setting. Objectives:To explore UK GP and NP views on and experiences of prescribing antibiotics for RTIs in primary care OOH services. Methods:Thirty semi-structured interviews were conducted with GPs and NPs working in primary care OOH services. Inductive thematic analysis was used to analyse data. Results:The research shows that factors particular to OOH influence antibiotic prescribing, including a lack of patient follow-up, access to patient GP records, consultation time, working contracts and implementation of feedback, audit and supervision. NPs reported perceptions of greater accountability for their prescribing compared with GPs and reported they had longer consultations during which they were able to discuss decisions with patients. Participants agreed that more complex cases should be seen by GPs and highlighted the importance of consistency of decision making, illness explanations to patients as well as a perception that differences in clinical training influence communication with patients and antibiotic prescribing decisions. Conclusions:Environmental and social factors in OOH services and a mixed healthcare workforce provide unique influences on antibiotic prescribing for RTIs, which would need to be considered in tailoring interventions that promote prudent antibiotic prescribing in OOH services.
| S-EPMC5890663 | biostudies-literature
Project description:BackgroundThe early life course is assumed to be a critical phase for childhood obesity; however the significance of single factors and their interplay is not well studied in childhood populations.ObjectivesThe investigation of pre-, peri- and postpartum risk factors on the risk of obesity at age 2 to 9.MethodsA case-control study with 1,024 1:1-matched case-control pairs was nested in the baseline survey (09/2007-05/2008) of the IDEFICS study, a population-based intervention study on childhood obesity carried out in 8 European countries in pre- and primary school settings. Conditional logistic regression was used for identification of risk factors.ResultsFor many of the investigated risk factors, we found a raw effect in our study. In multivariate models, we could establish an effect for gestational weight gain (adjusted OR = 1.02; 95%CI 1.00-1.04), smoking during pregnancy (adjusted OR = 1.48; 95%CI 1.08-2.01), Caesarian section (adjusted OR = 1.38; 95%CI 1.10-1.74), and breastfeeding 4 to 11 months (adjusted OR = 0.77; 95%CI 0.62-0.96). Birth weight was related to lean mass rather than to fat mass, the effect of smoking was found only in boys, but not in girls. After additional adjustment for parental BMI and parental educational status, only gestational weight gain remained statistically significant. Both, maternal as well as paternal BMI were the strongest risk factors in our study, and they confounded several of the investigated associations.ConclusionsKey risk factors of childhood obesity in our study are parental BMI and gestational weight gain; consequently prevention approaches should target not only children but also adults. The monitoring of gestational weight seems to be of particular importance for early prevention of childhood obesity.
| S-EPMC3923715 | biostudies-literature
Project description:ObjectivesHeart failure (HF) is a commonly occurring health problem with high mortality and morbidity. If potential cases could be detected earlier, it may be possible to intervene earlier, which may slow progression in some patients. Preferably, it is desired to reuse already measured data for screening of all persons in an age group, such as general practitioner (GP) data. Furthermore, it is essential to evaluate the number of people needed to screen to find one patient using true incidence rates, as this indicates the generalisability in the true population. Therefore, we aim to create a machine learning model for the prediction of HF using GP data and evaluate the number needed to screen with true incidence rates.Design, settings and participantsGP data from 8543 patients (-2 to -1 year before diagnosis) and controls aged 70+ years were obtained retrospectively from 01 January 2012 to 31 December 2019 from the Nivel Primary Care Database. Codes about chronic illness, complaints, diagnostics and medication were obtained. Data were split in a train/test set. Datasets describing demographics, the presence of codes (non-sequential) and upon each other following codes (sequential) were created. Logistic regression, random forest and XGBoost models were trained. Predicted outcome was the presence of HF after 1 year. The ratio case:control in the test set matched true incidence rates (1:45).ResultsSole demographics performed average (area under the curve (AUC) 0.692, CI 0.677 to 0.706). Adding non-sequential information combined with a logistic regression model performed best and significantly improved performance (AUC 0.772, CI 0.759 to 0.785, p<0.001). Further adding sequential information did not alter performance significantly (AUC 0.767, CI 0.754 to 0.780, p=0.07). The number needed to screen dropped from 14.11 to 5.99 false positives per true positive.ConclusionThis study created a model able to identify patients with pending HF a year before diagnosis.
| S-EPMC9438066 | biostudies-literature
Project description:Pragmatic randomised clinical trials could use existing electronic health records (EHRs) to identify trial participants, perform randomisation, and to collect follow-up data. Achieving adequate informed consent in routine care and clinician recruitment have been identified as key barriers to this approach to clinical trials. We propose a model where written informed consent for a pragmatic comparative effectiveness trial is obtained in advance by the research team, recorded in the EHR, and then confirmed by the general practitioner (GP) at the time of enrolment. The EHR software then randomly assigns a patient to one of two treatments. Follow-up data is collected in the EHR. Twenty-two of 23 GPs surveyed (96%) were 'definitely' or 'probably' comfortable with confirming consent. Twenty-one out of 23 GPs (91%) were 'definitely' or 'probably' comfortable with a patient being randomised to one of two comparable drugs during a routine consultation. Twenty-two out of 23 GPs (96%) were 'definitely' or 'probably' comfortable with allowing the electronic system to randomise a patient to drug A or drug B and generate a prescription. Ten out of 23 GPs (43%) identified time constraints as the main hurdle to conducting this sort of research in the primary care setting. On average, it was felt that 6.5 min, in addition to a usual consult, would be acceptable to complete enrolment. Our survey found this model of a comparative effectiveness trial to be acceptable to the majority of GPs.
| S-EPMC5956547 | biostudies-literature