Marco Geraci

How active are our children? Findings from the Millennium Cohort Study

Objective To describe levels of physical activity, sedentary time and adherence to Chief Medical Officers (CMO) physical activity guidelines among primary school-aged children across the UK using objective accelerometer-based measurements. Design Nationally representative prospective cohort study. Setting Children born across the UK, between 2000 and 2002. Participants 6497 7-year-old to 8-year-old singleton children for whom reliable accelerometer data were available for at least 10 h a day for at least 2 days. Main outcome measures Physical activity in counts per minute (cpm); time spent in sedentary and moderate-to-vigorous intensity physical activity (MVPA); proportion of children meeting CMO guidelines (≥60 min/day MVPA); average daily steps. Explanatory measures Gender, ethnicity, maternal current/most recent occupation, lone parenthood status, number of children in the household and country/region of residence. Results The median daily physical activity level was 595 cpm (IQR 507, 697). Children spent a median of 60 min (IQR 47–76) in MVPA/day and were sedentary for a median of 6.4 h/day (IQR 6–7). Only 51% met CMO guidelines, with girls (38%) less active than boys (63%). Children took an average of 10 229 (95% CI (8777 to 11 775)) steps each day. Children of Indian ethnicity were significantly less active overall than all other ethnic groups. Children of Bangladeshi origin and those living in Northern Ireland were least likely to meet CMO guidelines. Conclusions Only half of 7-year-old children in the UK achieve recommended levels of physical activity, with significant gender, ethnic and geographic variations. Longitudinal studies are needed to better understand the relevance of these (in)activity patterns for long-term health and well-being. In the meantime population-wide efforts to boost physical activity among young people are needed which are likely to require a broad range of policy interventions.

Low-Dose Maintenance Therapy With Infliximab Prevents Postsurgical Recurrence of Crohn's Disease

BACKGROUND & AIMS Infliximab might prevent postsurgical recurrence of Crohns disease. However, it is unclear whether long-term therapy is necessary and whether alternative strategies could be applied to minimize potential side effects and reduce the costs of treatment. METHODS We performed a prospective cohort study in 12 consecutive patients, treated immediately after surgery with maintenance infliximab (5 mg/kg), who did not have clinical or endoscopic evidence of disease recurrence after 24 months; they were followed up for an additional year. Infliximab treatment was then discontinued; patients with disease recurrence, based on endoscopy (Rutgeerts score, >or=2), were given lower doses of infliximab (starting with 1 mg/kg) to re-establish mucosal integrity. Surrogate markers of disease activity (fecal calprotectin [FC], C-reactive protein, and erythrocyte sedimentation rate) were assessed after each infliximab dose. RESULTS None of the patients had clinical or endoscopic recurrence of Crohns disease 3 years after surgery. However, discontinuation of infliximab caused endoscopic recurrence after 4 months in 10 of 12 patients (83%). All 10 patients then were treated again with infliximab, which, at a dose of 3 mg/kg every 8 weeks, restored and maintained mucosal integrity for 1 year. Among the surrogate markers, FC levels correlated with endoscopic scores (Wald test, P < .0001). CONCLUSIONS Long-term maintenance therapy with infliximab is required to maintain mucosal integrity in patients after surgery for Crohns disease. However, a dose of 3 mg/kg (a 40% reduction from the standard dose) was sufficient to avoid disease recurrence, determined by endoscopy, in all patients at 1 year. FC levels correlate with mucosal status at different infliximab doses.

Linear quantile mixed models

Dependent data arise in many studies. Frequently adopted sampling designs, such as cluster, multilevel, spatial, and repeated measures, may induce this dependence, which the analysis of the data needs to take into due account. In a previous publication (Geraci and Bottai in Biostatistics 8:140–154, 2007), we proposed a conditional quantile regression model for continuous responses where subject-specific random intercepts were included to account for within-subject dependence in the context of longitudinal data analysis. The approach hinged upon the link existing between the minimization of weighted absolute deviations, typically used in quantile regression, and the maximization of a Laplace likelihood. Here, we consider an extension of those models to more complex dependence structures in the data, which are modeled by including multiple random effects in the linear conditional quantile functions. We also discuss estimation strategies to reduce the computational burden and inefficiency associated with the Monte Carlo EM algorithm we have proposed previously. In particular, the estimation of the fixed regression coefficients and of the random effects’ covariance matrix is based on a combination of Gaussian quadrature approximations and non-smooth optimization algorithms. Finally, a simulation study and a number of applications of our models are presented.

Quality control methods in accelerometer data processing: defining minimum wear time.

Background When using accelerometers to measure physical activity, researchers need to determine whether subjects have worn their device for a sufficient period to be included in analyses. We propose a minimum wear criterion using population-based accelerometer data, and explore the influence of gender and the purposeful inclusion of children with weekend data on reliability. Methods Accelerometer data obtained during the age seven sweep of the UK Millennium Cohort Study were analysed. Children were asked to wear an ActiGraph GT1M accelerometer for seven days. Reliability coefficients(r) of mean daily counts/minute were calculated using the Spearman-Brown formula based on the intraclass correlation coefficient. An r of 1.0 indicates that all the variation is between- rather than within-children and that measurement is 100% reliable. An r of 0.8 is often regarded as acceptable reliability. Analyses were repeated on data from children who met different minimum daily wear times (one to 10 hours) and wear days (one to seven days). Analyses were conducted for all children, separately for boys and girls, and separately for children with and without weekend data. Results At least one hour of wear time data was obtained from 7,704 singletons. Reliability increased as the minimum number of days and the daily wear time increased. A high reliability (r = 0.86) and sample size (n = 6,528) was achieved when children with ≥ two days lasting ≥10 hours/day were included in analyses. Reliability coefficients were similar for both genders. Purposeful sampling of children with weekend data resulted in comparable reliabilities to those calculated independent of weekend wear. Conclusion Quality control procedures should be undertaken before analysing accelerometer data in large-scale studies. Using data from children with ≥ two days lasting ≥10 hours/day should provide reliable estimates of physical activity. It’s unnecessary to include only children with accelerometer data collected during weekends in analyses.

Comparative incidence patterns and trends of gonadal and extragonadal germ cell tumors in England, 1979 to 2003

It is believed that gonadal and extragonadal germ cell tumors (GCTs) arise from primordial germ cells and may have similar etiopathogenesis. Unlike testicular GCTs, there has been limited comprehensive population‐based analysis of ovarian and extragonadal GCTs.

Survival from cancer in teenagers and young adults in England, 1979–2003

Cancer is the leading cause of disease-related death in teenagers and young adults aged 13–24 years (TYAs) in England. We have analysed national 5-year relative survival among more than 30 000 incident cancer cases in TYAs. For cancer overall, 5-year survival improved from 63% in 1979–84 to 74% during 1996–2001 (P<0.001). However, there were no sustained improvements in survival over time among high-grade brain tumours and bone and soft tissue sarcomas. Survival patterns varied by age group (13–16, 17–20, 21–24 years), sex and diagnosis. Survival from leukaemia and brain tumours was better in the youngest age group but in the oldest from germ-cell tumours (GCTs). For lymphomas, bone and soft tissue sarcomas, melanoma and carcinomas, survival was not significantly associated with age. Females had a better survival than males except for GCTs. Most groups showed no association between survival and socioeconomic deprivation, but for leukaemias, head and neck carcinoma and colorectal carcinoma, survival was significantly poorer with increasing deprivation. These results will aid the development of national specialised service provision for this age group and identify areas of clinical need that present the greatest challenges.

Changes in cancer incidence in teenagers and young adults (ages 13 to 24 years) in England 1979‒2003

Cancer for teenagers and young adults represents a major source of morbidity and mortality. Trends in cancer incidence can provide pointers concerning how changes in the environment and in personal behavior affect cancer risks.

Comparison of radiolabeled isatin analogs for imaging apoptosis with positron emission tomography

INTRODUCTION Caspase-3 is one of the executioner caspases activated as a result of apoptosis. Radiolabeled isatins bind to caspase-3 with high affinity and are potential tracers for use with positron emission tomography to image apoptosis. We compared the ability of two novel radiolabeled isatins, [18F]WC-IV-3 and [11C]WC-98, to detect caspase-3 activation in a rat model of cycloheximide-induced liver injury. METHODS Male Sprague-Dawley rats were treated with cycloheximide and then imaged with microPET 3 h later with [18F]WC-IV-3 and [11C]WC-98. Biodistribution studies were also performed simultaneously, with caspase-3 activation verified by fluorometric enzyme assay and Western blots. RESULTS MicroPET imaging studies demonstrated similar behavior of both tracers but with a lower maximum peak with [11C]WC-98 than with [18F]WC-IV-3. Biodistribution studies demonstrated increased uptake of both tracers in the liver and spleen, but this was statistically significant only in the liver with both compounds. The level of [18F]WC-IV-3 uptake appeared to correlate roughly with rates of caspase-3 activation by the enzyme assay, but the magnitude of difference between treated and control groups was lower than that observed in previously published data with [18F]WC-II-89, another radiolabeled isatin analog. Activation was also confirmed in the liver and spleen but not in fat by Western blot. CONCLUSION [18F]WC-IV-3 uptake appears to correlate with increased caspase-3 enzyme activity, but the dynamic range of uptake of these two tracers appears to be less than that seen with [18F]WC-II-89. Studies are ongoing to verify these results in other animal models of apoptosis.

Increasing rates of cervical cancer in young women in England: An analysis of national data 1982-2006

Background:In England, cervical cancer is the second most common cancer in women aged under 35 years. Overall incidence of cervical cancer has decreased since the introduction of the national screening programme in 1988 but recent trends of incidence in young women have not been studied in detail.Methods:Information on 71 511 incident cases of cervical cancer in England, 1982–2006, in 20–79-year-olds was extracted from a national cancer registration database. Changes in incidence were analysed by age group, time period and birth cohort. Poisson regression was used to estimate annual percentage change (APC).Results:Overall incidence, during 1982–2006, fell significantly from 213 to 112 per million person years. However, in 20–29-year-olds, after an initial fall, incidence increased significantly during 1992–2006, (APC 2.16). In 30–39-year-olds incidence stabilised during the latter part of the study period. The pattern was most marked in the North East, Yorkshire and the Humber and East Midlands regions. Birth cohorts that were initially called for screening between 60–64 and 35–39 years of age show an incidence peak soon after the age of presumed first screen, whereas younger birth cohorts show a peak at about 35 years of age. Incidence in the 1977–1981 birth cohort has increased relative to that among women born between 1962 and 1976.Conclusion:These results have implications for cervical screening, human papilloma virus vaccination and other public health interventions targeting young people.

Cancer mortality in 13 to 29-year-olds in England and Wales, 1981-2005

We examined cancer mortality at ages 13–29 years in England and Wales between 1981 and 2005, a total of 20 026 deaths over approximately 303 million person-years (mpy) at risk by sex, age group and time period. Overall, the mortality rate was 65.6 per mpy. Malignant neoplasms of the central nervous system showed the highest rate (8.5), followed by myeloid and monocytic leukaemia (6.6), lymphoid leukaemia (6.4), malignant bone tumours (5.4) and non-Hodgkins lymphoma (5.2). These groups together accounted for almost 50% of all cancer deaths. The mortality rate for males (72.4) was 23% higher than for females (58.6) (P-value <0.0001). Males showed significantly higher mortality rates than females in almost all diagnostic groups, in general, mortality increasing with age (P-value <0.0001). There were significant decreases in mortality over time, the annual percentage change between 1981 and 2005 being minus 1.86 (95% confidence interval −2.09 to −1.62). Cancer groups with the highest mortality differed from those with the highest incidence.