It is now twenty years since Wertheimer and Leeper (1979) published the first study suggesting an association between residential exposure to extremely low frequency magnetic fields (EMF) and childhood cancer. Ever since, this has been a controversial issue with the findings from several, but not all, subsequent epidemiological studies being consistent with an association, particularly with respect to residential exposure and childhood leukaemia (Portier and Wolfe, 1998). However, many of the reports have been based on small numbers of exposed cases, and despite intense experimental research no known biophysical mechanism to explain an effect has been established.We conducted a pooled analysis based on primary data from nine studies on EMF and childhood leukaemia, addressing three specific questions:1. Do the combined results of these studies indicate that there is an association between EMF exposure and childhood leukaemia risk, which is larger than one would expect from random variability?2. Does adjustment for confounding from socioeconomic class, mobility, level of urbanization, detached/not detached dwelling, and level of traffic exhaust change the results? 3. Do the combined data support the existence of the so-called wire code paradox, that is, a stronger association between proxy measures of EMF and cancer than between direct measurements and cancer? METHODSThe original plan for this project was to include all European studies that addressed the question of an association between EMF and childhood leukaemia and were based on either 24 or 48 hour magnetic field measurements or calculated fields. At the time five such studies were reported (Feychting and Ahlbom, 1993; Olsen et al, 1993;Verkasalo et al, 1993;Tynes and Haldorsen, 1997;Michaelis et al, 1998). In addition, a nationwide childhood cancer study was in progress and near completion in the UK (UKCCS, 1999). Since we were not aware of any other European study to be published in the near future, the inclusion of the UK study would give us a complete set of European studies. We felt that if we could also incorporate new studies from non-European countries this pooled analysis would be up to date and presumably stay current for several years. We were aware of three more studies in other parts of the world with compatible information that were all nearly A pooled analysis of magnetic fields and childhood leukaemia Summary Previous studies have suggested an association between exposure to 50-60 Hz magnetic fields (EMF) and childhood leukaemia. We conducted a pooled analysis based on individual records from nine studies, including the most recent ones. Studies with 24/48-hour magnetic field measurements or calculated magnetic fields were included. We specified which data analyses we planned to do and how to do them before we commenced the work. The use of individual records allowed us to use the same exposure definitions, and the large numbers of subjects enabled more precise estimation of risks at high exposure levels. For the 3203 children with leukae...

For rehabilitation professionals engaged in the treatment of osteoarthritis (OA), it is standard practice to perform objective assessments of physical function (using both physical performance and self-report measures) to obtain a picture of patient status. These assessments also serve as a baseline value for estimating changes (treatment effects) over time. While reliability and validity of some commonly used physical performance measures have been investigated in an OA population, most require further research regarding clinical utility and responsiveness. 14 Physical performance measures have often been criticized, as detailed testing of their measurement properties has not been extensively reported. 14,22,33 Measures of responsiveness have commonly been reported as statistically significant change scores, which are useful in establishing the threshold of change needed beyond measurement error. 10 Investigation of minimal clinically important differences (MCIDs) of physical performance measures is warranted, as these have become commonly used outcome measures in the treatment of OA. 8,12,17,[35][36][37] At present, the responsiveness (in terms of MCID) of the timed up-and-go (TUG) test, 40-meter self-paced walk test (40-m SPWT), 30-second chair stand (30 CST), and 20-cm step test has not been investigated in T T STUDY DESIGN: Prospective cohort study. T T OBJECTIVES:To establish the major clinically important improvement (MCII) of the timed upand-go test (TUG), 40-meter self-paced walk test (40-m SPWT), 30-second chair stand (30 CST), and a 20-cm step test in patients with hip osteoarthritis (OA) undergoing physiotherapy treatment. As a secondary aim, a comparison of methods was employed to evaluate the effect of method on the reported MCII. T T BACKGROUND: Minimal clinically importantdifference scores are commonly used by rehabilitation professionals to determine patient response following treatment. A gold standard for calculating MCII has yet to be determined, which has resulted in problems of interpretation due to varied results. T T METHODS:As part of a randomized controlled trial, 65 patients were randomized into a physiotherapy treatment group for hip OA, in which they completed 4 physical performance measures at baseline and 9 weeks. Upon completion of physiotherapy, patients assessed their response to treatment on a 15-point global rating of change scale (GRCS). MCII was estimated using 3 variations of an anchor-based method, based on the patient's opinion. T T RESULTS:A comparison of 3 methods resulted in the following change scores being best associated with our definition of MCII: a reduction equal to or greater than 0.8, 1.4, and 1.2 seconds for the TUG; an increase equal to or greater than 0.2, 0.3, and 0.2 m/s for the 40-m SPWT; an increase equal to or greater than 2.0, 2.6, and 2.1 repetitions for the 30 CST; an increase equal to or greater than 5.0, 12.8, and 16.4 steps for the 20-cm step test. T T CONCLUSION:The variation in methods provided very different results. This illustrates the impor...

The associations between ALL and parental ages did not disappear when children with Down syndrome were excluded, suggesting an additional explanation beyond known links. The strong ALL association with parity may be because of an unknown environmental risk factor.

Summary A nationwide case-control study was conducted in New Zealand, to test hypotheses about the role of infections in the aetiology of childhood leukaemia. Children aged 0-14 years with leukaemia were matched on age and sex to controls selected from birth records. Case ascertainment was virtually complete and 121 (92%) of 131 eligible case families took part. The participation rate among the 303 first-choice eligible controls was 69%. Home interviews and serological tests were conducted. Adjusted relative risks were estimated by logistic regression. There was an increased risk of leukaemia in relation to reported influenza infection of the child during the first year of life (adjusted odds ratio 6.8, 95% confidence interval 1.8-25.7). This could be a chance finding due to multiple comparisons, and it should be tested elsewhere. Some key variables relevant to Greaves' hypothesis were not associated with B-cell precursor acute lymphoblastic leukaemia (numbers of infections and vaccinations, firstborn status, attendance at preschool groups), although a small effect could not be ruled out with a study of this size. Leukaemia risk was higher among children in poorer social circumstances, and this was true for all eligible children as well as for the participants.

SummaryBackground-Results from case-control studies have shown an increased risk of acute lymphoblastic leukaemia (ALL) in young children born by caesarean delivery, and prelabour caesarean delivery in particular; however, an association of method of delivery with childhood leukaemia subtypes has yet to be established. We therefore did a pooled analysis of data to investigate the association between childhood leukaemia and caesarean delivery.

The associations between childhood acute lymphoblastic leukemia (ALL) and several proxies of early stimulation of the immune system, that is, day-care center attendance, birth order, maternally reported common infections in infancy, and breastfeeding, were investigated by using data from 11 case-control studies participating in the Childhood Leukemia International Consortium (enrollment period: 1980-2010). The sample included 7,399 ALL cases and 11,181 controls aged 2-14 years. The data were collected by questionnaires administered to the parents. Pooled odds ratios and 95% confidence intervals were estimated by unconditional logistic regression adjusted for age, sex, study, maternal education, and maternal age. Day-care center attendance in the first year of life was associated with a reduced risk of ALL (odds ratio = 0.77, 95% confidence interval: 0.71, 0.84), with a marked inverse trend with earlier age at start (P < 0.0001). An inverse association was also observed with breastfeeding duration of 6 months or more (odds ratio = 0.86, 95% confidence interval: 0.79, 0.94). No significant relationship with a history of common infections in infancy was observed even though the odds ratio was less than 1 for more than 3 infections. The findings of this large pooled analysis reinforce the hypothesis that day-care center attendance in infancy and prolonged breastfeeding are associated with a decreased risk of ALL.

Background Acute leukemia is the most common cancer in children under 15 years of age; 80% are acute lymphoblastic leukemia (ALL) and 17% are acute myeloid leukemia (AML). Childhood leukemia shows further diversity based on cytogenetic and molecular characteristics, which may relate to distinct etiologies. Case–control studies conducted worldwide, particularly of ALL, have collected a wealth of data on potential risk factors and in some studies, biospecimens. There is growing evidence for the role of infectious/immunologic factors, fetal growth, and several environmental factors in the etiology of childhood ALL. The risk of childhood leukemia, like other complex diseases, is likely to be influenced both by independent and interactive effects of genes and environmental exposures. While some studies have analyzed the role of genetic variants, few have been sufficiently powered to investigate gene–environment interactions. Objectives The Childhood Leukemia International Consortium (CLIC) was established in 2007 to promote investigations of rarer exposures, gene–environment interactions and subtype-specific associations through the pooling of data from independent studies. Methods By September 2012, CLIC included 22 studies (recruitment period: 1962–present) from 12 countries, totaling approximately 31 000 cases and 50 000 controls. Of these, 19 case–control studies have collected detailed epidemiologic data, and DNA samples have been collected from children and child–parent trios in 15 and 13 of these studies, respectively. Two registry-based studies and one study comprising hospital records routinely obtained at birth and/or diagnosis have limited interview data or biospecimens. Conclusions CLIC provides a unique opportunity to fill gaps in knowledge about the role of environmental and genetic risk factors, critical windows of exposure, the effects of gene–environment interactions and associations among specific leukemia subtypes in different ethnic groups.

Some previous studies have suggested that home pesticide exposure before birth and during a child's early years may increase the risk of childhood leukemia. To further investigate this, we pooled individual level data from 12 case-control studies in the Childhood Leukemia International Consortium (CLIC). Exposure data were harmonized into compatible formats. Pooled analyses were undertaken using multivariable unconditional logistic regression. The odds ratio (ORs) for acute lymphoblastic leukaemia (ALL) associated with any pesticide exposure shortly before conception, during pregnancy and after birth were 1.39 (95% confidence interval (CI) 1.25, 1.55) (using (2,785 cases, 3635 controls), 1.43 (95% CI 1.32, 1.54) (5,055 cases, 7,370 controls) and 1.36 (95% CI 1.23, 1.51) (4,162 cases 5,179 controls), respectively. Corresponding ORs for risk of acute myeloid leukaemia (AML) were 1.49 (95% CI 1.02, 2.16) (173 cases, 1,789 controls), 1.55 (95% CI 1.21, 1.99) (344 cases, 4,666 controls) and 1.08 (95% CI 0.76, 1.53) (198 cases, 2,655 controls) respectively. There was little difference by type of pesticide used. The relative similarity in ORs between leukaemia types, time periods and pesticide types may be explained by similar exposure patterns and effects across the time periods in ALL and AML, participants’ exposure to multiple pesticides, or recall bias. Although some recall bias is likely, until a better study design can be found to investigate associations between home pesticide use and childhood leukaemia in an equally large sample, it would appear prudent to limit the use of home pesticides before and during pregnancy, and during childhood.