Household Food Insecurity Is Associated With Physical Activity in Youth and Young Adults With Diabetes: A Cross-Sectional Study.

BACKGROUND: Physical activity (PA) is essential for optimal diabetes management. Household food insecurity (HFI) may negatively affect diabetes management behaviors. The purpose of this study was to cross-sectionally examine the association between HFI and PA in youth and young adults (YYA) with type 1 (N = 1998) and type 2 (N = 391) diabetes from the SEARCH for Diabetes in Youth Study. METHODS: HFI was measured with the US Household Food Security Survey Module. PA was measured with the International Physical Activity Questionnaire Short Form. Walking, moderate-intensity PA (excluding walking), vigorous-intensity PA, moderate- to vigorous-intensity PA, and total PA were estimated as minutes per week, while time spent sitting was assessed in minutes per day. All were modeled with median regression. Meeting PA guidelines or not was modeled using logistic regression. RESULTS: YYA with type 1 diabetes who experienced HFI spent more time walking than those who were food secure. YYA with type 2 diabetes who experienced HFI spent more time sitting than those who were food secure. CONCLUSIONS: Future research should examine walking for leisure versus other domains of walking in relation to HFI and use objective PA measures to corroborate associations between HFI and PA in YYA with diabetes.

A retrospective analysis of the factors associated with surgical checklist compliance using data from a local health unit in Italy, 2018-2021.

RATIONALE: Since its publication, the World Health Organization Surgical Safety Checklist (SSC) has been progressively adopted by healthcare providers around the world to monitor and safeguard the delivery of surgeries. In one Italian region's health system, the SSC and other two surgery-specific checklists were supplemented by a document that records any non-conformity (NC) arising from the safety checks. AIMS AND OBJECTIVES: In this study, we investigated the factors associated with NCs using data from a local health unit (LHU). The secondary aim of this study was to explore the potential impact of the coronavirus crisis on surgical checklist compliance. METHODS: We used data on surgical activity from the Modena LHU between 2018 and 2021 and the accompanying NC documents. The primary goal was to estimate the relative risk (RR) of NCs according to several factors, including checklist incompleteness and surgery class (elective, urgent or emergency), using Poisson regression. A similar analysis was performed separately for 2018-2019 and 2020-2021 to assess the COVID-19 potential impact. RESULTS AND CONCLUSIONS: Checklist compliance in the LHU was 95%, with the presence of NCs in about 7% of surgeries. The factors that increased the RR were incompleteness of the checklist (adjusted RR = 3.12; 95% confidence interval [CI] = 2.86-3.40), urgent surgeries (adjusted RR [aRR] = 1.59; 95% CI = 1.47-1.72), emergencies (aRR = 2.09; 95% CI = 1.15-3.79), and surgeries with more than four procedures (aRR = 1.64; 95% CI = 1.41-1.92). Most notably, the RR for incomplete checklists showed a negative association with NCs before the COVID-19 outbreak but positive afterwards. Checklist compliance was overall satisfactory, though the observation of noncompliant checklists of about 1000 per year suggests there is still room for improvement. Moreover, attention to the checklist best practices and organization of outpatient workload may have been affected by the exceptional circumstances of the pandemic.

Trends in Resources for Neonatal Intensive Care at Delivery Hospitals for Infants Born Younger Than 30 Weeks' Gestation, 2009-2020.

Importance: In an ideal regionalized system, all infants born very preterm would be delivered at a large tertiary hospital capable of providing all necessary care. Objective: To examine whether the distribution of extremely preterm births changed between 2009 and 2020 based on neonatal intensive care resources at the delivery hospital. Design, Setting, and Participants: This retrospective cohort study was conducted at 822 Vermont Oxford Network (VON) centers in the US between 2009 and 2020. Participants included infants born at 22 to 29 weeks' gestation, delivered at or transferred to centers participating in the VON. Data were analyzed from February to December 2022. Exposures: Hospital of birth at 22 to 29 weeks' gestation. Main Outcomes and Measures: Birthplace neonatal intensive care unit (NICU) level was classified as A, restriction on assisted ventilation or no surgery; B, major surgery; or C, cardiac surgery requiring bypass. Level B centers were further divided into low-volume (<50 inborn infants at 22 to 29 weeks' gestation per year) and high-volume (≥50 inborn infants at 22 to 29 weeks' gestation per year) centers. High-volume level B and level C centers were combined, resulting in 3 distinct NICU categories: level A, low-volume B, and high-volume B and C NICUs. The main outcome was the change in the percentage of births at hospitals with level A, low-volume B, and high-volume B or C NICUs overall and by US Census region. Results: A total of 357 181 infants (mean [SD] gestational age, 26.4 [2.1] weeks; 188 761 [52.9%] male) were included in the analysis. Across regions, the Pacific (20 239 births [38.3%]) had the lowest while the South Atlantic (48 348 births [62.7%]) had the highest percentage of births at a hospital with a high-volume B- or C-level NICU. Births at hospitals with A-level NICUs increased by 5.6% (95% CI, 4.3% to 7.0%), and births at low-volume B-level NICUs increased by 3.6% (95% CI, 2.1% to 5.0%), while births at hospitals with high-volume B- or C-level NICUs decreased by 9.2% (95% CI, -10.3% to -8.1%). By 2020, less than half of the births for infants at 22 to 29 weeks' gestation occurred at hospitals with high-volume B- or C-level NICUs. Most US Census regions followed the nationwide trends; for example, births at hospitals with high-volume B- or C-level NICUs decreased by 10.9% [95% CI, -14.0% to -7.8%) in the East North Central region and by 21.1% (95% CI, -24.0% to -18.2%) in the West South Central region. Conclusions and Relevance: This retrospective cohort study identified concerning deregionalization trends in birthplace hospital level of care for infants born at 22 to 29 weeks' gestation. These findings should serve to encourage policy makers to identify and enforce strategies to ensure that infants at the highest risk of adverse outcomes are born at the hospitals where they have the best chances to attain optimal outcomes.

The Gut Microbial Profile of Preclinical Crohn's Disease Is Similar to That of Healthy Controls.

BACKGROUND AND AIMS: It is unclear whether microbial dysbiosis plays an etiologic role in Crohn's disease (CD) or is the result of protracted inflammation. Here, we test the hypothesis that dysbiosis predates clinical CD in asymptomatic first-degree relatives (FDRs) of CD patients: normal (FDR1), with borderline inflammation (FDR2), and with frank, very early inflammation (FDR3). METHODS: The gut microbial diversity was tested in ileocecal biopsies through next generation sequencing of the 16S rRNA gene in 10 healthy controls (HCs), 22 patients with active, untreated CD, and 25 FDRs (9 FDR1; 12 FDR2; 4 FDR3). The metagenomic functions of 41 microbiome-related processes were inferred by Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) analysis. RESULTS: Compared with HCs, alpha diversity in CD patients was decreased, with an observed decrease in Faecalibacterium prausnitzii and increase in Bacteroides fragilis. In FDRs, microbial diversity was unchanged compared with HCs. In Operational Taxonomic Units and PICRUSt Principal coordinates and component analyses, the ellipse centroid of FDRs was diagonally opposed to that of CD patients, but close to the HC centroid. In both analyses, statistically significant differences in terms of beta diversity were found between CD and HC but not between FDR and HC. CONCLUSIONS: In FDRs (including FDR3-who bear preclinical/biologic onset disease), we found that the microbial profile is remarkably similar to HC. If confirmed in larger studies, this finding suggests that clinical CD-associated dysbiosis could result from the changed microenvironment due to disease evolution over time.

Opioid Prescription Patterns for Adults With Longstanding Disability and Inflammatory Conditions Compared to Other Users, Using a Nationally Representative Sample.

OBJECTIVES: To investigate the opioid prescription patterns for adults with longstanding physical disability and inflammatory conditions, compared to a mixed group of other opioid users, after excluding cancer patients. DESIGN: Nationally representative cross-sectional study, 2010-2014. SETTING: Medical Expenditure Panel Survey (MEPS). PARTICIPANTS: The participants (N=7134) were adults who participated in MEPS and had at least 1 opioid prescription, did not have cancer, and were between 18 years and 64 years of age. The participants were grouped as longstanding physical disability (group 1), inflammatory conditions (group 2), and a mixed group with at least 1 opioid prescription during the 2-year study period (comparison group). Participants with both groups of conditions were excluded. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Morphine milligram equivalent (MME) doses for each participant were cumulated over a 2-year panel period. RESULTS: By using quantile regression, cumulative MME in groups 1 and 2 was higher than the comparison group across all the percentiles, and differences between condition groups and comparison group became larger in higher percentiles. Participants in group 1 had the highest cumulative MME in 75th and 90th percentiles after controlling for other covariates. CONCLUSIONS: This study documented the opioid prescription patterns for patients with longstanding physical disability or inflammatory conditions. All indexed groups (groups 1 and 2) had higher MME use compared to the comparison group.

An increased Bax/Bcl-2 ratio in circulating inflammatory cells predicts primary response to infliximab in inflammatory bowel disease patients.

BACKGROUND: Predicting the response of inflammatory bowel disease (IBD) patients to infliximab (IFX) is an unmet clinical need. The expression and density of transmembrane tumor necrosis factor-α in circulating leukocytes maybe directly related to response by promoting apoptosis. AIM: We tested the hypothesis that direct apoptosis assessment by real-time polymerase chain reaction evaluation of pro-apoptotic (Bax) and anti-apoptotic (Bcl-2) proteins in peripheral blood mononuclear cells (PBMCs) might be associated with response to IFX. METHODS: IFX naïve patients (Crohn's disease, 32 and ulcerative colitis, 20; 35 responders and 17 non-responders) were evaluated for Bax and Bcl-2 mRNA expression levels before and 2 weeks after the first infusion. In a subset of patients, apoptosis was also evaluated using flow cytometry. RESULTS: After the first infusion, Bax increased more in responders than in non-responders (0.7± 0.38 vs 0.81 ± 0.32 and 0.86 ± 0.37 vs 0.87 ± 0.45, respectively, p = 0.071). Bcl-2 decreased more in responders than in non-responders (0.71 ± 0.12 vs 0.63 ± 0.13 and 0.81 ± 0.28 vs 0.77 ± 0.27, respectively, p = 0.038). The Bax/Bcl-2 ratio increased more in responders than in non-responders (0.99 ± 0.5 vs 1.3 ± 0.51 and 1.03 ± 0.17 vs 1.1 ± 0.28, respectively, p = 0.005). The Bax/Bcl-2 ratio was able to predict response in 33/52 patients and was correlated to flow cytometry-assessed apoptosis (r = 0.911; p < 0.001). CONCLUSIONS: An increased Bax/Bcl-2 ratio in PBMCs was associated with therapeutic response to IFX in IBD patients.

Tissue studies in screened first-degree relatives reveal a distinct Crohn's disease phenotype.

BACKGROUND: First-degree relatives of patients with Crohn's disease (CD) are at risk of developing the disease with 5% to 15% reported to be affected over time. Yet, a much greater proportion of them (>40%) shows features of "subclinical inflammation" with elevated intestinal inflammatory markers such as fecal calprotectin. The meaning of these findings is unclear in the absence of tissue data. METHODS: Thirty-eight asymptomatic first-degree relatives of patients with CD underwent ileocolonoscopy and other tests including fecal calprotectin. All known causes of intestinal inflammation were carefully excluded. Age and gender-matched controls consisted of 10 individuals who underwent colonoscopy for other reasons. Histology was scored based on known methods. RESULTS: Compared with controls, the relatives had significantly greater median values for fecal calprotectin and histological scores. In relatives, endoscopy identified 3 different phenotypes: (1) normal, (2) with minor lesions (aphthae or small superficial erosions), and (3) with typical CD inflammation. Based on the histological scores, the clustering analysis produced 3 corresponding highly separated clusters (61%, 26%, and 13% of the total, respectively) with divisive coefficient D = 0.94. When followed up (on the average for 53 mo), individuals in the second cluster had histological scores similar to baseline values (P = 0.12). CONCLUSIONS: Tissue studies in first-degree relatives of patients with CD reveal 3 distinct groups: normal, with minimal inflammation, and with frank disease. The second cluster represents a novel phenotype, which does not seem to develop the disease over time. These findings explain previous observations of "subclinical inflammation" in such population.

Pre-clinical Crohn's disease: diagnosis, treatment and six year follow-up.

Diagnosis of Crohn's disease is usually made at a symptomatic stage. However diagnosis at a pre-clinical stage might provide valuable information on etiology/pathogenesis and allow early intervention to alter its natural history. We describe here the case of a 27 year old woman who was diagnosed with Crohn's disease at a completely asymptomatic stage and followed up for more than six years. She was part of an ongoing screening study in first degree relatives of Crohn's disease patients. At diagnosis, colonoscopy showed modest inflammation and few superficial ulcerations and erosions in the ileo-cecal valve and the terminal ileum. Fecal calprotectin was only modestly elevated. Intestinal permeability was also increased. During follow-up and while still asymptomatic the patient was sequentially treated with therapeutic doses of 5-ASA, budesonide, azathioprine and infliximab in an attempt to stop disease progression. Only infliximab appeared capable of inducing profound mucosal healing-however the disease recurred several months after the medication was ceased. Over time, quantification by immunohistochemistry of a number of cell types and cytokines revealed a positive correlation between CD4-CD25-FOXP3 (Treg) cell number and inflammation, a finding potentially consistent with tissue resistance to Tregs' activity.

Median percent change: a robust alternative for assessing temporal trends.

A typical summary statistic for temporal trends is the average percent change (APC). The APC is estimated by using a generalized linear model, usually under the assumption of linearity on the logarithmic scale. A serious limitation of least-squares type estimators is their sensitivity to outliers. The goal of this study is twofold: firstly, we propose a robust and easy-to-compute measure of the temporal trend based on the median of the rates (median percent change - MPC), rather than their mean, under the hypothesis of constant relative change; secondly, we investigate the performance of several models for estimating the rate of change when some of the most common model assumptions are violated. We provide some guidance on the practices of the estimation of temporal trends when using different models under different circumstances. The robustness property of the median is assessed in a simulation study, which shows that the MPC provides strong reductions in estimation bias and variance in presence of outliers. We also demonstrate how a mathematical property of the median helps addressing the issue of zero counts when estimating trends on the log-scale. Finally, we analyzed an English cancer registration dataset to illustrate the proposed method. We believe that, as a good practice, both APC and MPC should be presented when sensitivity issues arise.

Predictors of non-response in a UK-wide cohort study of children's accelerometer-determined physical activity using postal methods.

OBJECTIVES: To investigate the biological, social, behavioural and environmental factors associated with non-consent, and non-return of reliable accelerometer data (≥2 days lasting ≥10 h/day), in a UK-wide postal study of children's activity. DESIGN: Nationally representative prospective cohort study. SETTING: Children born across the UK, between 2000 and 2002. PARTICIPANTS: 13 681 7 to 8-year-old singleton children who were invited to wear an accelerometer on their right hip for 7 consecutive days. Consenting families were posted an Actigraph GT1M accelerometer and asked to return it by post. PRIMARY OUTCOME MEASURES: Study consent and reliable accelerometer data acquisition. RESULTS: Consent was obtained for 12 872 (94.5%) interviewed singletons, of whom 6497 (50.5%) returned reliable accelerometer data. Consent was less likely for children with a limiting illness or disability, children who did not have people smoking near them, children who had access to a garden, and those who lived in Northern Ireland. From those who consented, reliable accelerometer data were less likely to be acquired from children who: were boys; overweight/obese; of white, mixed or 'other' ethnicity; had an illness or disability limiting daily activity; whose mothers did not have a degree; who lived in rented accommodation; who exercised once a week or less; who had been breastfed; were from disadvantaged wards; had younger mothers or lone mothers; or were from households with just one, or more than three children. CONCLUSIONS: Studies need to encourage consent and reliable data return in the wide range of groups we have identified to improve response and reduce non-response bias. Additional efforts targeted at such children should increase study consent and data acquisition while also reducing non-response bias. Adjustment must be made for missing data that account for missing data as a non-random event.

Early diagnosis and treatment of postoperative endoscopic recurrence of Crohn's disease: partial benefit by infliximab--a pilot study.

BACKGROUND: Current data indicate that infliximab-given immediately after surgery-may be very effective in preventing postsurgical recurrence of Crohn's disease. However, it is unknown whether a similar benefit would result from early diagnosis and treatment, rather than prevention of endoscopic recurrence. AIMS: The primary outcome of this study was to clarify whether infliximab, given after diagnosis of postoperative endoscopic recurrence of Crohn's diseases (Rutgeerts score ≥ 2) can induce endoscopic remission (score <2) at 54 weeks. The secondary outcomes were improvement in the endoscopic score and clinical recurrence at 54 weeks. METHODS: In this prospective open label multicenter pilot study 43 patients with ileocolonic Crohn's disease subjected to curative surgery underwent colonoscopy 6 months after surgery. Patients with endoscopic recurrence (Rutgeerts score ≥2) were treated with either mesalamine 800 mg tid or infliximab 5 mg/kg bw on a maintenance basis. Colonoscopy was performed after 54 weeks of therapy. RESULTS: A total of 24/43 patients were diagnosed with endoscopic recurrence at 6 months. Thirteen were treated with infliximab and 11 with mesalamine. None of the 11 mesalamine-treated patients had endoscopic remission at 54 weeks. Two had clinical recurrence at 8 and 9 months. Fifty-four percent of patients treated with infliximab had endoscopic remission at 54 weeks (P = 0.01) while 69% had an improvement in the endoscopic score. None had clinical recurrence. CONCLUSIONS: Treatment of postsurgical endoscopic lesions by infliximab appears superior to mesalamine. However, a sizeable proportion of patients did not fully benefit from this strategy.

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

BACKGROUND: 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. METHODS: All malignant GCTs and all central nervous system (CNS) GCTs with benign and uncertain behavior that were registered in England in the age group 0 to 84 years from 1979 to 2003 were included in the current study. Incidence rates were calculated and adjusted to the world standard population. RESULTS: There were 33,364 GCTs (92.5% testes, 3.9% ovary, 3.2% extragonadal) in individuals aged 0 to 84 years. The CNS was the most common extragonadal site. An initial peak in incidence at ages 0 to 4 years of nongerminomas was observed at all sites except ovary. Second incidence peaks between ages 10 to 39 years that were more marked among males also were observed at all sites. The ages at these incidence peaks varied by site and were 10 to 14 years (CNS), 15 to 19 years (ovary), 25 to 29 years (other extragonadal sites), and 30 to 34 years (testes). A statistically significant increase in incidence over time was observed in germinomas (testes, CNS) and nongerminomas (testes, ovary). CONCLUSIONS: The age-incidence patterns observed suggested a common initiation of GCTs in embryonic/fetal life with variable rates of tumor progression as a result of subsequent events that may be site specific. The authors concluded that future genetic studies should consider GCTs from all sites to enable a better understanding of their etiology.

Cancer at ages 15-29 years: the contrasting incidence in India and England.

BACKGROUND: There has been a steady increase in published research from Europe and North America on the epidemiology of cancers in young people. There are limited data from the developing world. We contrast the incidence of cancer at ages 15-29 years in India and England. PROCEDURE: Malignant neoplasms in those aged 15-29 years registered during 2001-2003 in five urban population-based cancer registries (PBCRs) of India and in eight PBCRs in England were included. Site-based classification was used. Age-standardized incidence rates were expressed per 100,000 person years. RESULTS: In India, 4,864 (5.8%) of 84,450 cases and in England, 8,137 (1.2%) of 65,6752 cancer cases occurred in those aged 15-29 years. For this age group, the incidence rate for males and females in India were 12.91 and 14.19, and in England were 27.75 and 28.88, respectively. In males aged 15-29 years, the three most common cancers in India were leukemia, lymphoma, and central nervous system tumors and in England were cancers of male genital organs, lymphoma, and leukemia. Cancers of female genital organs, breast, and leukemia were most common in females in India and cancers of female genital organs, lymphoma, and melanoma in England. For cancers of mouth, stomach, and gall bladder, the incidence was higher in India. CONCLUSION: Incidence of cancer at ages 15-29 years in England is higher at most sites than in India. Variation in environmental exposures between the two countries might be an explanation. Under-ascertainment of cases and gender bias in seeking healthcare may also influence reported incidence rates in India.

The contrasting age-incidence patterns of bone tumours in teenagers and young adults: Implications for aetiology.

Bone tumours comprise 0.2% of cancers overall but 5.7% in 15-24 year olds. To explore the relationship with adolescence we have analysed age-incidence patterns of bone tumours in a large national dataset. Data on incident cases of bone tumours in 0-84 year olds in England, 1979-2003, were extracted from national cancer registration data. Incidence rates per million person-years by 5-year age-group, sex, morphology and primary site were calculated and adjusted to the world standard population. Nine thousand one hundred forty-six cases were identified giving an overall age-standardized rate of 7.19 per million person-years. The distribution by morphology was: osteosarcoma, 34.2%; chondrosarcoma, 27.2%; Ewing sarcoma, 19.3%; other, 19.4%. The distribution varied by age. Ewing sarcoma was most common in 0-9 year olds, osteosarcoma in 10-29 year olds and chondrosarcoma in 30-84 year olds. 29.2% of all tumours occurred in 0-24 year olds. Highest incidence of osteosarcoma and Ewing sarcoma in females was in 10-14 year olds. In males, peak incidence occurred at 15-19 years and exceeded that in females. Chondrosarcoma incidence steadily increased with age. The proportions of Ewing sarcomas occurring in respective bones were consistent with those of the adult skeleton by weight. In osteosarcoma tumours of long bones of lower limb were markedly over-represented in the adolescent peak, being six times more than at any other site. Variation in incidence patterns with age and site suggests pubertal bone growth to be a key factor in osteosarcoma while different biological pathways could be relevant for Ewing sarcoma.

Relationship between height at diagnosis and bone tumours in young people: a meta-analysis.

OBJECTIVE: Some evidence exists that patients with osteosarcoma and Ewing sarcoma are taller than the general population. However, previous studies are under-powered, lack comprehensive data and show inconsistencies. METHODS: Relevant studies linking osteosarcoma and Ewing sarcoma with height at diagnosis were identified in two major online databases, Medline (1950 to 2009) and Embase (1980 to 2009). Outcomes in individual studies were reported as standard deviation (SD) scores or percentages of study population with height at diagnosis above the median of the reference population. We performed separate random-effects meta-analyses for each outcome and tumour type. RESULTS: 14 studies examined the height of patients with osteosarcoma or Ewing sarcoma. Meta-analyses on SD scores found patients with osteosarcoma were 0.260 SD (95% CI: 0.088-0.432) taller than the reference population (five studies). A meta-analysis on percentages found 62% (95% CI: 57%-67%) of patients were estimated to have a height above the median (six studies). Patients with Ewing sarcoma were 0.096 SD (95% CI 0.004-0.188) taller (four studies). Only one study reported the percentage of Ewing sarcoma patients with height above the median. CONCLUSION: The average height of patients with osteosarcoma, but not Ewing sarcoma, was significantly above the average height of the reference population by 2-3 centimetres. The observed differences indicate the involvement of pubertal longitudinal bone growth in osteosarcoma development while different biological pathways could be relevant for Ewing sarcoma.

Diagnosis and assessment of Crohn's disease: the present and the future.

Diagnosis of Crohn's disease (CD) is often challenging and requires the utmost precision and perseverance in defining location, extent, severity and type of disease (inflammatory vs stricturing/penetrating), as well as in excluding septic complications and extraintestinal manifestations. Endoscopy and histology remain, as of today, the best tests for initial diagnosis of CD. Increasingly important roles are played by imaging techniques (small bowel MRI, computed tomographic enterography and intestinal ultrasound) and noninvasive markers of disease such as fecal calprotectin and specific autoantibodies. Here, we will review the main tools presently available to make the initial diagnosis of intestinal and perianal CD, to evaluate the response to treatment and to diagnose disease recurrence after surgery. Finally, we will discuss some of the future diagnostic challenges in CD.

Are reported increases in incidence of primary CNS tumours real? An analysis of longitudinal trends in England, 1979-2003.

Reported increases in the incidence of CNS tumours in the developed world in the 1970s to 1990s have been a cause for concern and debate. It still remains to be adequately answered whether these increases are true or an artefact of changes in diagnostic and registration practices. Using high-quality national cancer registration data, we have analysed incidence trends for each major histological subgroup of CNS tumour (2000 World Health Organisation (WHO) classification) registered in those aged 0-84 years for the whole of England during the period 1979 through 2003. 134,509 primary CNS tumours of malignant, benign and uncertain behaviour located in the brain, meninges, spinal cord, cranial nerves, other parts of the central nervous system and in the pituitary and pineal glands were registered. In summary, we present the single largest nationwide study on the longitudinal incidence trends of CNS tumours. The increase in incidence observed in the 1970s and 1980s was mainly in the young and the elderly and has now plateaued and may even be decreasing. There is however variation in trends by histology. The incidence of some histological sub-groups has continued to increase until the most recent period of analysis. Much of the initial increase can be attributed to the emergence of much more widely available neuroimaging, while the most recent incidence changes for specific sub-groups of CNS tumours appear to be due to greater diagnostic specificity leading to a shift in registered categories. However, the trends for high-grade astrocytomas and other gliomas need further observation and investigation.

Low-dose maintenance therapy with infliximab prevents postsurgical recurrence of Crohn's disease.

BACKGROUND & AIMS: Infliximab might prevent postsurgical recurrence of Crohn's 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 Crohn's 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 Crohn's 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.

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

BACKGROUND: 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. METHODS: Data on 39,129 neoplasms in individuals ages 13 to 24 years who were diagnosed in England from 1979 to 2003 were analyzed. Variability in incidence by time period and differences in the time trends by age group, sex, and geographic region were analyzed using generalized linear models. RESULTS: Incidence rates of leukemias, lymphomas, central nervous system, bone, and germ cell tumors; melanoma; and carcinomas of the thyroid, ovary, cervix, and colon/rectum increased over time (all P < .01); whereas the incidence of carcinomas of the stomach and bladder decreased (both P < .01). These changes were consistent by age, sex, and region for most neoplasms. Melanoma incidence stabilized in southern England by 1993 but continued to increase in northern England (P = .001). The increase in non-Hodgkin lymphoma was greater in individuals ages 20 to 24 year than in younger individuals, but the increase in Hodgkin lymphoma was confined to individuals ages 13 to 14 years. CONCLUSIONS: The changes in incidence rates may have been caused in part by environmental changes and in part by behavioral changes in young individuals. Some of these results can be used to inform public health campaigns, which can be constructed to encourage better lifestyle choices by young individuals.