Extremely low-frequency magnetic fields and survival from childhood acute lymphoblastic leukemia: an international follow-up study.

A previous US study reported poorer survival in children with acute lymphoblastic leukemia (ALL) exposed to extremely low-frequency magnetic fields (ELF-MF) above 0.3 µT, but based on small numbers. Data from 3073 cases of childhood ALL were pooled from prospective studies conducted in Canada, Denmark, Germany, Japan, UK and US to determine death or relapse up to 10 years from diagnosis. Adjusting for known prognostic factors, we calculated hazard ratios (HRs) and 95% confidence intervals (CI) for overall survival and event-free survival for ELF-MF exposure categories and by 0.1 µT increases. The HRs by 0.1 µT increases were 1.00 (CI, 0.93-1.07) for event-free survival analysis and 1.04 (CI, 0.97-1.11) for overall survival. ALL cases exposed to >0.3 µT did not have a poorer event-free survival (HR=0.76; CI, 0.44-1.33) or overall survival (HR=0.96; CI, 0.49-1.89). HRs varied little by subtype of ALL. In conclusion, ELF-MF exposure has no impact on the survival probability or risk of relapse in children with ALL.

Disease Activity Score 28-ESR bears a similar relationship to treatment decisions across different rheumatologists, but misclassification is too frequent to replace physician judgement.

OBJECTIVES: To determine whether physician factors are associated with disease activity status in RA, independently of 28-joint disease activity score (DAS28)-ESR and to re-evaluate DAS28-ESR misclassification rates for identifying active disease in usual practice. METHODS: A prospective observational study of outpatients with RA seen by 17 rheumatologists across New Zealand. Active disease was defined by an increase in therapy together with a reason of 'active disease'; very low disease activity was defined by a decrease in therapy together with a reason of 'patient well'. The independent physician effect was assessed using logistic regression. Sensitivity and specificity of current DAS28-ESR thresholds were calculated. RESULTS: In 511 patients, 178 had active disease, 220 had low disease activity, 37 had very low disease activity and 76 had uncertain disease activity status. There was no independent effect of physician upon active disease status (P = 0.16) with DAS28-ESR [(OR) 3.7] explaining around 50% of the variability in active disease status. There was a trend towards an independent effect of physician upon very low disease activity status (P = 0.06) and greater variability in the distribution of DAS28-ESR for patients in very low disease activity. DAS28-ESR thresholds showed a significant risk of misclassification for active disease. CONCLUSIONS: DAS28-ESR discriminates satisfactorily between groups of patients with active and non-active disease, with no evidence of additional physician-specific factors to explain disease activity status. However, DAS28-ESR is not as good for discriminating remission from non-remission status. There are appreciable probabilities of misclassification error, which make DAS28-ESR inappropriate as a sole guide for treatment decisions.

Population-based survival of children in New Zealand diagnosed with cancer during 1990-1993.

In this study, we have aimed to characterise the survival of all 0-14 year-old New Zealand children who were diagnosed with cancer during 1990-1993. Four hundred and nine children were followed up using two largely independent sources. We calculated Kaplan-Meier survival probabilities and investigated various prognostic factors using the Cox model. Five-year survival for all cancers was 66% (95% confidence interval (CI) 62-71%) and for acute lymphoblastic leukaemia it was 70% (CI 62-79%). Cancers with particularly favourable prognoses (followed by their respective 5-year survival probabilities) included: retinoblastoma 100% (CI 74-100%), Hodgkin's disease 93% (CI 79-100%), non-Hodgkin's lymphoma 87% (CI 73-100%) and osteosarcoma 91% (CI 74-100%). Cancers with poor prognoses included: neuroblastoma 35% (CI 14-56%), rhabdomyosarcoma 42% (CI 14-70%) and central nervous system tumours 49% (CI 38-60%). Girls with any cancer had a significantly lower risk of death than boys. Generally, survival for childhood cancers in New Zealand increased greatly between 1961-1965 and 1990-1993. Nevertheless, outcomes for some cancers remained poor.

A randomised placebo controlled trial of delipidated, deglycolipidated Mycobacterium vaccae as immunotherapy for psoriatic arthritis.

OBJECTIVES: To test the hypothesis that PVAC, delipidated, deglycolipidated heat killed Mycobacterium vaccae, is an effective and safe treatment for psoriatic arthritis (PsA). This treatment has shown promising results in psoriasis. METHODS: 36 patients with PsA in two centres were studied in this double blind, placebo controlled, randomised trial. Patients were randomised to receive two intradermal injections of 50 micro g PVAC or placebo and were followed up for 24 weeks. The primary end point was the Psoriatic Arthritis Response Criteria (PsARC), a composite measure based on changes in joint tenderness and swelling scores and physician and patient global assessments. RESULTS: The PsARC response at either 12 or 24 weeks was achieved by 9/18 (50%) placebo and 9/18 (50%) PVAC patients (p = 1.0). No significant differences in the Psoriasis Activity and Severity Index (PASI), patient or physician global assessments, CRP, or Health Assessment Questionnaire score over time were found between the two groups. However, changes in the pain visual analogue scale over time did differ between the two groups (p = 0.006): at 24 weeks the mean score in the PVAC group had declined by 19.2 mm and in the placebo group had increased by 4.8 mm. PVAC was well tolerated with no increased incidence of adverse events compared with placebo. CONCLUSIONS: PVAC was not shown to be as effective as immunotherapy for PsA. The striking response to placebo in this study reinforces the importance of adequately controlling therapeutic trials in PsA.

Extended report: nail disease in psoriatic arthritis--clinically important, potentially treatable and often overlooked.

OBJECTIVES: To examine the relationship between the severity of nail disease and characteristics of psoriatic arthritis (PsA). We also wished to assess the clinical management of nail disease in patients with PsA. METHODS: We studied 69 patients with PsA at two visits. On the first visit, a rheumatology assessment of joint, skin and nail disease was made. On the second visit, a detailed dermatology assessment of skin and nails was made. Nail disease was analysed using a 20-nail psoriasis nail severity score (PNSS). RESULTS: There were 57 (83%) patients with clinical evidence of psoriatic nail disease. Although 66 (96%) patients had been treated for skin disease, only one (1%) had received any treatment for nail disease. Severe nail disease measured by the PNSS correlated with severe skin psoriasis as indicated by the percentage of body surface area affected by psoriasis (r = 0.34, P = 0.004) and physician global assessment of psoriasis (r = 0.45, P<0.001). Patients with distal interphalangeal (DIP) joint disease had higher PNSS scores (P = 0.03). The PNSS was also associated with unremitting and progressive arthritis (P<0.001), and correlated with Stanford health assessment questionnaire (HAQ) (r = 0.34, P = 0.004), depression (r = 0.39, P<0.001) and anxiety (r = 0.34, P = 0.004) scores. Compared with dermatology assessment, the rheumatology examination of nail disease had a positive predictive value of 84% and negative predictive value of 83%. CONCLUSIONS: In patients with PsA, the severity of nail disease correlates with indicators of severity of both skin and joint disease. Although rheumatologists can adequately screen for nail disease, the management of this aspect of PsA is often overlooked.

Clinical assessment of sacroiliitis and HLA-B27 are poor predictors of sacroiliitis diagnosed by magnetic resonance imaging in psoriatic arthritis.

OBJECTIVE: To determine the frequency and clinical predictors of sacroiliitis diagnosed by magnetic resonance imaging (MRI) in a psoriatic arthritis (PsA) population. METHODS: The studied comprised 103 patients with PsA. A careful clinical assessment for sacroiliitis was made from history and examination, and HLA-B27 testing was performed. Sixty-eight patients underwent tilted coronal fat-saturated T1-weighted and STIR MRI of the sacroiliac joints. RESULTS: Clinical features of moderate or severe sacroiliitis were found in 24/68 (35%) patients. MRI features of sacroiliitis were found in 26/68 (38%) patients. Clinical features of sacroiliitis were present in 14/42 (33%) with normal MRI scans and 10/26 (38%) with abnormal scans (normal vs abnormal scans, P = 0.7). The presence of sacroiliitis on MRI was associated with restricted spinal movements (P = 0.004) and the duration of PsA (P = 0.04). There was no correlation between HLA-B27 and sacroiliitis diagnosed by MRI. CONCLUSION: Sacroiliitis diagnosed by MRI occurs commonly in PsA but is difficult to detect clinically.

Economic effects of childhood cancer on families.

OBJECTIVE: To assess the financial impact of childhood cancer on families. METHODS: This was a cross-sectional survey of parents caring for children who were diagnosed with cancer during the period 1990-1993. Self-administered questionnaires were completed by the parents of 237 children from throughout New Zealand with different types of cancer. Dollar amounts were adjusted to the equivalent of December 2000. RESULTS: Eighty-six per cent of the 192 living children were well or in remission. A further 45 children had died. The average extra amount spent, because of the child's illness, by the family of a living child in the 30 days prior to participation in the study was NZ$220 (SD NZ$330). On average, this was 13% of the family income after tax. After reported entitlement to compensation from various sources was allowed for, families were left with a mean deficit of NZ$157 (SD NZ$278) for the 30 days. Twelve families had a shortfall of more than NZ$500, including three families that had a shortfall of more than NZ$1000. Expenditure was greater for those whose children spent more time in hospital (P = 0.003). There was no significant association between the total cost and the distance travelled to the treatment centre (P = 0.96). For 24 families, after-tax income in the month prior to participation in the study was at least NZ$500 lower than it had been in the month before the child's diagnosis. Thirty-seven per cent of families reported that they needed to borrow money because of the financial effects of the child's illness. Bereaved parents spent an average of NZ$3065 (SD NZ$2168) on funeral expenses. CONCLUSION: There is a large financial burden on families who have a child with cancer.

Case-control study of parental age, parity and socioeconomic level in relation to childhood cancers.

BACKGROUND: Parental ages, parity, and social class have been found in some studies to be associated with particular childhood cancers. Further investigation is warranted because of conflicting findings, biases, and the need to test specific hypotheses. METHODS: A case-control study was conducted (England and Wales, ages 0-14 years). Cases were ascertained from the National Registry of Childhood Tumours, and were born and diagnosed during 1968-1986. Birth record controls were matched 1:1 to cases on date of birth, sex and area. Information on variables of interest for both groups came from birth records. In all, 10 162 pairs could contribute to matched analyses. RESULTS: The odds ratio (OR) for retinoblastoma resulting from assumed new germ cell mutations among children of fathers aged > or =45 years was 3.0 (95% CI : 0.2-41.7). The risk of childhood acute lymphoblastic leukaemia (ALL) was significantly higher among children of older mothers and fathers, and significant trends with increasing mothers' (P < 0.001) and fathers' (P = 0.002) ages were found. There was a strong and significant protective effect of increasing parity on risk of childhood ALL. The adjusted OR for parity of > or =5 (versus 0) was 0.5 (95% CI : 0.3-0.8). Children in more deprived communities had a lower risk of ALL; but this was not significant after confounders were allowed for. There was no significant effect of social class based on parental occupation on ALL risk, but the numbers were small in those analyses. CONCLUSIONS: 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.

Impact of childhood cancer on the mental health of parents.

BACKGROUND: When a child is diagnosed with cancer, the family experiences great stress and disruption to daily life. As part of a national study in New Zealand, we evaluated the mental health of mothers and fathers of children with cancer, making comparisons to parents of children from the general population. PROCEDURE: This was a cross-sectional study. All children diagnosed with cancer at ages 0-14 years in New Zealand during a defined period were ascertained from the national cancer registry and other databases. The population-based comparison children were selected using national birth records. Parents from both groups completed self-administered questionnaires containing the General Health Questionnaire (GHQ-12) and other measures. The analyses included 218 mothers and 179 fathers of children with cancer, and 266 mothers and 224 fathers of children in the comparison group. Multivariate regression was used to adjust for demographic and socioeconomic characteristics, life events, and social support. RESULTS: Mothers and fathers of children with cancer had poorer GHQ-12 and mood rating scores than those of controls. The adjusted difference in the mean total GHQ-12 score (comparing mothers of children with cancer to mothers of controls) was 2.2 (95% confidence interval 1.3-3.2). The 12 items of the GHQ were each scored 0-3, and the total score was the sum, so 2 points is a small difference. For fathers the difference was 1.5 (95% confidence interval 0.6-2.4). Some subgroups of cancer group parents had poorer emotional health scores than others, including those with poor social support and no paid employment and also those who were bereaved. CONCLUSIONS: We found statistically significant but small differences between the mental health of parents of children with cancer and controls. The small differences suggest that as a group the parents of children with cancer are relatively resilient.

A pooled analysis of magnetic fields and childhood leukaemia.

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 leukaemia and 10 338 control children with estimated residential magnetic field exposures levels < 0.4 microT, we observed risk estimates near the no effect level, while for the 44 children with leukaemia and 62 control children with estimated residential magnetic field exposures >/= 0.4 microT the estimated summary relative risk was 2.00 (1.27-3.13), P value = 0.002). Adjustment for potential confounding variables did not appreciably change the results. For North American subjects whose residences were in the highest wire code category, the estimated summary relative risk was 1.24 (0.82-1.87). Thus, we found no evidence in the combined data for the existence of the so-called wire-code paradox. In summary, the 99.2% of children residing in homes with exposure levels < 0.4 microT had estimates compatible with no increased risk, while the 0.8% of children with exposures >/= 0.4 microT had a relative risk estimate of approximately 2, which is unlikely to be due to random variability. The explanation for the elevated risk is unknown, but selection bias may have accounted for some of the increase.

Infections, vaccinations, and the risk of childhood leukaemia.

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.

Childhood cancer in New Zealand 1990 to 1993.

An epidemiological study of childhood cancer in New Zealand identified 409 children aged 0 to 14 years with malignant neoplasms newly diagnosed between 1990 and 1993 inclusive. The original microscopic material on which the diagnoses were based was reviewed in 398 cases and the neoplasms were allocated into the 12 major groupings and 48 further subcategories of the International Classification of Childhood Cancer (ICCC). The pathology reviewers agreed with group and subcategory classification of the confirmed cancers in all but one case of acute leukemia and three cancers of the central nervous system. Changes were also made in the FAB classification of three cases of acute non-lymphocytic leukemia and in the further subcategorisation of three Hodgkin's lymphomas and ten astrocytomas. The results show a high level of diagnostic accuracy for confirmed childhood neoplasms in that time period. Nine of 15 cases of malignant melanoma notified to the study were not confirmed for various reasons, which included a change in the pathological diagnosis in four cases. Compared with Victoria (Australia), New Zealand has a high incidence rate of lymphomas in boys and an unusual female preponderance of Wilms' tumor cases.

An assessment of spatial clustering of leukaemias and lymphomas among young people in New Zealand.

STUDY OBJECTIVE: To assess spatial clustering of childhood leukaemias and lymphomas in New Zealand, using a national dataset from a country with no nuclear installations. DESIGN: New Zealand Map Grid coordinates, derived from the birth addresses of cases and controls were used in clustering analyses that applied Cuzick and Edwards' method. SETTING: The whole of New Zealand. PARTICIPANTS: The cases were ascertained from the New Zealand Cancer Registry. They were diagnosed with leukaemia or lymphoma at ages 0-14 years during the period 1976 to 1987. For Hodgkin's disease, the age range was extended to include those aged from 0-24 years. The cancer registrations were linked with national birth records, to obtain the birth addresses of the cases. The controls were selected at random from birth records, with matching to cases (1:1) on age and sex. The analyses included 600 cases and 600 controls. MAIN RESULTS: There was no statistically significant spatial clustering for any tumour group overall, including acute lymphoblastic leukaemia, acute nonlymphoblastic leukaemia, other leukaemias, non-Hodgkin's lymphomas, Hodgkin's disease, and all these combined. Significant clustering was found in a sub-analysis for one of three age specific subgroups of acute lymphoblastic leukaemia (ages 10-14 years, p = 0.003). CONCLUSION: The subgroup finding may have been real or a chance association, as several comparisons were made. This study found little evidence for spatial clustering of leukaemias or lymphomas in a population with no nuclear installations.

Electromagnetic field exposures and childhood leukaemia in New Zealand.

A nationwide case-control study of childhood leukaemia in New Zealand included measurements of electric and magnetic fields in children's homes. There was no significant association between leukaemia and the time-weighted average of the 50 Hz magnetic or electric fields in the bedroom and living (or daytime) room combined.

Electromagnetic field exposures and childhood cancers in New Zealand.

OBJECTIVES: To assess childhood cancer risks for electromagnetic field (EMF) exposures. METHODS: A case-control study was conducted in New Zealand. Cases (aged from zero to 14 years) were ascertained from national databases including the New Zealand Cancer Registry; 303 took part (participation rate, 88 percent). The 303 age- and gender-matched controls were selected randomly from birth records (participation, 69 percent). Mothers were interviewed about appliance exposures (all cases and controls), and 24-hour residential measurements of EMFs were made (leukemia cases and matched controls). RESULTS: For the various appliance exposures, there were some odds ratios (OR) above 1.0 and others below 1.0. For electric blanket use by the child before diagnosis, the adjusted ORs were: leukemia, 2.2 (95 percent confidence interval [CI] = 0.7-6.4); central nervous system cancers, ORs = 1.6 (CI = 0.4-7.1); and other solid cancers, OR = 2.4 (CI = 1.0-6.1). Leukemia risk was increased for the highest category of the mean measured bedroom magnetic field (> or = 0.2microT cf < 0.1 microT), with an adjusted OR of 15.5 (CI = 1.1-224). A gradient in OR with exposure was not shown (middle category: OR 1.4, CI = 0.3-7.6), and there was no association with exposure categorized into thirds based on controls' exposure. The adjusted OR for leukemia in relation to the measured daytime room magnetic field (> or = 0.2 microT cf < 0.1 microT) was 5.2 (CI = 0.9-30.8). CONCLUSIONS: This was a small study and multiple comparisons were made. The positive findings thus should be interpreted cautiously.

The accuracy and completeness of childhood cancer registration in New Zealand.

The New Zealand Cancer Registry (NZCR) is the main source of data on cancer incidence in New Zealand. The accuracy and completeness of registration of childhood cancers (ages zero to 14 years) were assessed during the conduct of a case-control study. Newly diagnosed children (1990-93) were ascertained from three sources: the NZCR; the Patient Management System (hospital admissions and discharges); and the separate Children's Cancer Registry. Pathology reviews were conducted to verify the diagnoses. Capture-recapture methods were used to assess the completeness of ascertainment. During the four-year period, 409 incident cases of childhood cancer were confirmed, giving an age-standardized incidence rate of 131 per million person-years (95 percent confidence interval = 119-144). The NZCR ascertained 395 (97 percent) of these children. In addition, the NZCR notified us of 43 other 'childhood cancer' registrations which were not confirmed as new cases of childhood cancer according to our eligibility criteria. The main reasons for these were coding errors (20 registrations), duplicates (seven), and a change in the pathological diagnosis as a result of the pathology review (seven). The capture-recapture estimate of the total number of incident cases was 410. Overall, the NZCR had good completeness for childhood cancers, but the number of unconfirmed registrations was larger than expected.

Childhood leukaemias in New Zealand: time trends and ethnic differences.

Registrations from the New Zealand Cancer Registry were used to examine time trends in the incidence of leukaemias among children aged 0-14. There was a statistically significant increase in the incidence of leukaemia among children aged 0-4 during 1953-57 to 1988-90. In this age group, the recorded incidence rate increased from 4.89 per 100,000 person-years in 1953-57 to 7.92 in 1988-90. During 1973-77 to 1988-90 (and probably in earlier years), the increase was due to an increase in acute lymphoblastic leukaemia (ALL). The trends were unlikely to be due to changes in diagnosis or case ascertainment. The childhood leukaemia trends might be related to trends in family size, maternal age, socioeconomic level or exposure to infections. However, there are uncertainties about the importance of these factors or about their trends. The incidence of acute non-lymphoblastic leukaemia (ANLL) decreased between 1968-72 and 1988-90. The time trends highlight the likely importance of environmental factors in the aetiology of childhood leukaemias in New Zealand. The risk of ALL was lower in the Maori than in the non-Maori population (relative risk Maori/non-Maori 0.74). The risk of ANLL was higher among Maori (relative risk 1.84).