Early infancy growth, body composition and type of feeding in late and moderate preterms.

BACKGROUND: Late and moderate preterm (LMPT) infants are at risk for adverse later life outcomes. We determined the association between feeding method at enrolment and growth and body composition of LMPT infants until 3 months corrected age (3mCA). METHODS: Infants born between 32+0 and 36+6 weeks of gestation (n = 107) were enrolled up to 4 weeks corrected age and stratified according to feeding at enrolment. We performed anthropometric measurements at enrolment, term equivalent age (TEA) and 3mCA, including skinfold measurements and body composition using dual X-ray absorptiometry (DEXA). RESULTS: Feeding method at enrolment was associated with fat mass (FM) (breast 554.9 g, mixed 716.8 g, formula 637.7 g, p = 0.048), lean body mass (LM) (2512 g, 2853 g, 2722 g, respectively, p = 0.009) and lean mass index (LMI) (10.6 kg/m2, 11.6 kg/m2,11.2 kg/m2 respectively, p = 0.008) at TEA, but not 3mCA. Breastfed infants demonstrated greater increase in LM (breast 1707 g, mixed 1536 g, formula 1384 g, p = 0.03) and LMI (1.23 kg/m2, 0.10 kg/m2, 0.52 kg/m2, respectively, p = 0.022) between TEA and 3mCA. CONCLUSIONS: Breastfed LMPT infants have lower FM and greater LM increase and LMI increase up to 3mCA compared to formula or mixed-fed infants. These findings stress the importance of supporting breastfeeding in this population. IMPACT: Infants born late and moderate preterm age who are exclusively breastfed soon after birth gain more lean mass up to 3 months corrected age compared to mixed- or formula-fed infants. Breastfed infants have lower lean and fat mass at term equivalent age compared to mixed- and formula-fed infants. This is the first study exploring this population's growth and body composition in detail at 3 months corrected age. Our results underline the importance of supporting mothers to initiate and continue breastfeeding at least until 3 months corrected age.

Loss of ALK hotspot mutations in relapsed neuroblastoma.

ALK is the most commonly mutated oncogene in neuroblastoma with increased mutation frequency reported at relapse. Here we report the loss of an ALK mutation in two patients at relapse and a paired neuroblastoma cell line at relapse. ALK detection methods including Sanger sequencing, targeted next-generation sequencing and a new ALK Agena MassARRAY technique were used to detect common hotspot ALK variants in tumors at diagnosis and relapse from two high-risk neuroblastoma patients. Copy number analysis including single nucleotide polymorphism array and array comparative genomic hybridization confirmed adequate tumor cell content in DNA used for mutation testing. Case 1 presented with an ALK F1174L mutation at diagnosis with a variant allele frequency (VAF) ranging between 23.5% and 28.5%, but the mutation was undetectable at relapse. Case 2 presented with an ALK R1257Q mutation at diagnosis (VAF = 39%-47.4%) which decreased to <0.01% at relapse. Segmental chromosomal aberrations were maintained between diagnosis and relapse confirming sufficient tumor cell content for mutation detection. The diagnostic SKNBE1n cell line harbors an ALK F1174S mutation, which was lost in the relapsed SKNBE2c cell line. To our knowledge, these are the first reported cases of loss of ALK mutations at relapse in neuroblastoma in the absence of ALK inhibitor therapy, reflecting intra-tumoral spatial and temporal heterogeneity. As ALK inhibitors are increasingly used in the treatment of refractory/relapsed neuroblastoma, our study highlights the importance of confirming whether an ALK mutation detected at diagnosis is still present in clones leading to relapse.

Temporal clustering of neuroblastic tumours in children and young adults from Ontario, Canada.

BACKGROUND: The aetiology of neuroblastic tumours is likely to involve both genetic and environmental factors. A number of possible environmental risk factors have been suggested, including infection. If an irregular temporal pattern in incidence is found, this might suggest that a transient agent, such as an infection, is implicated. Previous work has found evidence for temporal clustering in children and young adults living in northern England. METHODS: We examined data from a second population-based registry from Ontario, Canada to determine whether there was evidence of temporal clustering of neuroblastic tumours. Cases diagnosed in children and young adults aged 0-19 years between 1985 and 2016 were extracted from the population-based Pediatric Oncology Group of Ontario Networked Information System (POGONIS). A modified version of the Potthoff-Whittinghill method was used to test for temporal clustering. Estimates of extra-Poisson variation (EPV) and standard errors (SE) were obtained. RESULTS: Eight hundred seventy-six cases of neuroblastic tumours were diagnosed during the study period. Overall, no evidence of temporal clustering was found between fortnights, between months or between quarters within years. However, significant EPV was found between years within the full study period (EPV = 1.05, SE = 0.25; P = 0.005). CONCLUSIONS: The findings are consistent with the possibility that a transient agent, such as an infection that is characterised by 'peaks and troughs' in its occurrence, might be implicated in the aetiology of neuroblastic tumours. However, this pattern may also reflect a long-term increase in the numbers of cases, rather than peaks and troughs.

Short-term effects of air pollution on daily asthma-related emergency department visits in an industrial city.

BACKGROUND: Epidemiological studies from Europe and North America have provided evidence that exposure to air pollution can aggravate symptoms in asthmatic patients. METHODS: Daily number of AEDv, air pollution levels (PM10, PM2.5, SO2, NO2 and CO) and meteorological variables was obtained from Jubail Industrial City, Saudi Arabia, for the period of 2007-11. Data were analyzed using a time-series approach. Relative risks (RRs) were estimated using Poisson regression. RESULTS: The associations between AEDv and PM10, PM2.5, SO2 and NO2 remained positive and statistically significant after mutual adjustment in the multi-pollutant model.The RR of AEDv increased by 5.4, 4.4, 3.4 and 2.2% per an inter-quartile range increase in SO2 (2.0 ppb), PM2.5 (36 µg/m3), NO2 (7.6 ppb) and PM10 (140 µg/m3), respectively. No significant associations between AEDv and CO were found. CONCLUSIONS: Current levels of ambient air pollution are associated with AEDv in this industrial setting in the Middle East. Greater awareness of environmental health protection and the implementation of effective measures to improve the quality of air in such settings would be beneficial to public health.

Constitutional and somatic rearrangement of chromosome 21 in acute lymphoblastic leukaemia.

Changes in gene dosage are a major driver of cancer, known to be caused by a finite, but increasingly well annotated, repertoire of mutational mechanisms. This can potentially generate correlated copy-number alterations across hundreds of linked genes, as exemplified by the 2% of childhood acute lymphoblastic leukaemia (ALL) with recurrent amplification of megabase regions of chromosome 21 (iAMP21). We used genomic, cytogenetic and transcriptional analysis, coupled with novel bioinformatic approaches, to reconstruct the evolution of iAMP21 ALL. Here we show that individuals born with the rare constitutional Robertsonian translocation between chromosomes 15 and 21, rob(15;21)(q10;q10)c, have approximately 2,700-fold increased risk of developing iAMP21 ALL compared to the general population. In such cases, amplification is initiated by a chromothripsis event involving both sister chromatids of the Robertsonian chromosome, a novel mechanism for cancer predisposition. In sporadic iAMP21, breakage-fusion-bridge cycles are typically the initiating event, often followed by chromothripsis. In both sporadic and rob(15;21)c-associated iAMP21, the final stages frequently involve duplications of the entire abnormal chromosome. The end-product is a derivative of chromosome 21 or the rob(15;21)c chromosome with gene dosage optimized for leukaemic potential, showing constrained copy-number levels over multiple linked genes. Thus, dicentric chromosomes may be an important precipitant of chromothripsis, as we show rob(15;21)c to be constitutionally dicentric and breakage-fusion-bridge cycles generate dicentric chromosomes somatically. Furthermore, our data illustrate that several cancer-specific mutational processes, applied sequentially, can coordinate to fashion copy-number profiles over large genomic scales, incrementally refining the fitness benefits of aggregated gene dosage changes.

Quantitative Computed Tomography (QCT) of the Distal Forearm in Men Using a Spiral Whole-Body CT Scanner - Description of a Method and Reliability Assessment of the QCT Pro Software.

The Mr F study investigates the pathogenesis of low trauma distal forearm fractures in men and includes volumetric bone mineral density (vBMD) measurements at the ultradistal forearm as there are no current data. A standard 64 slice CT scanner was used to determine if it was possible to adapt the existing Mindways quantitative computed tomography Pro software for measuring vBMD values at the hip and spine sites. For calculation of intra- and interobserver reliability 40 forearm scans out of the 300 available were chosen randomly. The images were analyzed using the Slice Pick module and Bone Investigational Toolkit. The 4% length of the radius was chosen by measuring the length of the radius from the scaphoid fossa distally to the radial head. The acquired image then underwent extraction, isolation, rotation, and selection of region of interest in order to generate a report on vBMD. A cross-sectional image was created to allow the generation of data on the cortical and trabecular components separately. Repeat analyses were undertaken by 3 independent observers who were blinded as to whether the image was from a participant with or without fracture. The images were presented in random order at each time point. The following parameters were recorded: cortical cross sectional area, total vBMD, trabecular vBMD, and cortical vBMD (CvBMD). Data were analyzed by calculating intraclass correlation coefficients for intra- and interobserver reliability. The lowest values occurred at the CvBMD with intraobserver reliability of 0.92 (95% confidence interval [CI] of 0.86-0.96) and interobserver reliability of 0.92 (95% CI 0.89-0.96). All other parameters had reliability values between 0.97 and 0.99 with tighter 95% CI than for CvBMD. The method of adapting the Mindways Pro software using a standard CT to produce vBMD and structural data at the ultradistal radius is reliable.

A geographical study of thyroid cancer incidence in north-west England following the Windscale nuclear reactor fire of 1957.

The Windscale nuclear reactor fire at Sellafield, United Kingdom, in October 1957 led to an uncontrolled release of iodine-131 (radioactive half-life, 8 d) into the atmosphere. Contamination from the accident was most pronounced in the counties of Cumbria and Lancashire, north-west England. Radioiodine concentrates in the thyroid gland producing an excess risk of thyroid cancer, notably among those exposed as children, which persists into later life. For an initial investigation of thyroid cancer incidence in north-west England, data were obtained on cases of thyroid cancer among people born during 1929-1973 and diagnosed during 1974-2012 while resident in England, together with corresponding populations. Incidence rate ratios (IRRs), with Poisson 95% confidence intervals (CIs), compared thyroid cancer incidence rates in Cumbria and in Lancashire with those in the rest of England. For those aged <20 years in 1958, a statistically significantly increased IRR was found for those diagnosed during 1974-2012 while living in Cumbria (IRR = 1.29; 95% CI 1.09-1.52), but the equivalent IRR for Lancashire was marginally non-significantly decreased (IRR = 0.91; 95% CI 0.80-1.04). This pattern of IRRs was also apparent for earlier births, and the significantly increased IRR in Cumbria extended to individuals born in 1959-1963, who would not have been exposed to iodine-131 from the Windscale accident. Moreover, significant overdispersion was present in the temporal distributions of the IRRs, so that Poisson CIs substantially underestimate statistical uncertainties. Consequently, although further investigations are required to properly understand the unusual patterns of thyroid cancer IRRs in Cumbria and Lancashire, the results of this preliminary study are not consistent with an effect of exposure to iodine-131 from the Windscale accident.

Fluoridation may not be linked with adverse health outcomes.

ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Community water fluoridation and health outcomes in England: a cross-sectional study. Young N, Newton J, Morris J, Morris J, Langford J, Iloya J, Edwards D, Makhani S, Verne J. Community Dent Oral Epidemiol 2015; 43:550-9. SOURCE OF FUNDING: Public Health England TYPE OF STUDY/DESIGN: Ecological (area based).

Temporal clustering of neuroblastic tumours in children and young adults from Northern England.

BACKGROUND: The aetiology of neuroblastic tumours is unclear with both genetic and environmental factors implicated. The possibility that an infectious agent may be involved has been suggested. 'Temporal clustering' occurs if cases display an irregular temporal distribution and may indicate the involvement of an agent that exhibits epidemicity. We tested for the presence and nature of temporal clustering using population-based data from northern England. METHODS: We extracted all cases of neuroblastic tumours diagnosed in children and young adults aged 0-24 years during 1968-2011 from the Northern Region Young Persons' Malignant Disease Registry. This is a population-based registry, covering a population of approximately 900,000 young persons, and includes all cases resident in northern England at the time of diagnosis. Tests for temporal clustering were applied using a modified version of the Potthoff-Whittinghill method. Estimates of extra-Poisson variation (ß) and standard errors (SEs) were obtained. RESULTS: 227 cases of neuroblastic tumours were diagnosed during the study period. All the analyses between fortnights and between months found significant extra-Poisson variation, with ß = 0.846 (SE = 0.310, P = 0.004) for the analysis between fortnights within months. Restricting the analyses to the 76 cases diagnosed at ages less than 18 months showed significant extra-Poisson variation between fortnights within months (ß = 1.532, SE = 0.866, P = 0.038), but not between months. In contrast, analyses of cases aged 18 months to 24 years showed significant extra-Poisson variation between quarters within years, as well as over shorter timescales. CONCLUSIONS: Transient environmental agents may be involved in the aetiology of neuroblastic tumours. The initiating factor might be a geographically-widespread agent that occurs in 'mini-epidemics'.

Trends in infant mortality rates in Hungary between 1963 and 2012.

AIM: This study investigated annual and seasonal death trends for infants of <1 year of age in Hungary between 1963 and 2012 and analysed commonly accepted risk factors. METHODS: Data on the numbers of live births and infant deaths were obtained from the published nationwide population register. Negative binomial regression was applied to investigate the yearly trends in rates and also the effect of possible risk factors - low birthweight, maternal education and sex - on infant mortality. Cyclic trends were investigated using logistic regression. RESULTS: Annual infant mortality declined significantly (p < 0.001) from 42.9 to 4.9 per 1000 live births per year during the study period and significantly increased (p < 0.001) in the low birthweight group and lower maternal education groups. A significant (p < 0.001) cyclic trend in mortality was revealed, with a peak in deaths in late February for all infants and a double peak, in May and November, in the group of cases who died during the early neonatal period. CONCLUSION: This Hungarian study suggests that there was a significant seasonal effect on neonatal and infant mortality at the end of winter between 1963 and 2012. We speculate that this may have been related to respiratory infections.

Cross-space-time clustering of childhood cancer in Great Britain: evidence for a common aetiology.

Previously, we identified space-time clustering in certain childhood cancers. This study aimed to determine whether there was cross-space-time clustering between different diagnostic groups. A total of 32,295 cases were diagnosed during 1969-1993. Cross-space-time clustering was analyzed by a second-order procedure based on Diggle's method. Locations were birth and diagnosis addresses. The following space-time combinations were examined: address and date of birth; address at birth and date of diagnosis; address and date of diagnosis. Cross-space-time clustering analyses considered clustering pairs of cases from two different diagnostic groups. Formal statistical significance was taken as p < 0.00067 and marginal significance 0.01 > p ≥ 0.00067. Based on address at birth and date of diagnosis, there was statistically significant cross-clustering between cases of HL and intracranial and intraspinal embryonal tumors (IIET), both aged 0-14 years (p < 0.0001). Based on address and date of birth, there was marginally significant cross-clustering between cases of lymphoid leukemia (LL) aged 5-14 years and Hodgkin lymphoma (HL) aged 0-14 years (p = 0.0019). Based on address and date of diagnosis there was marginally significant cross-clustering between cases of LL aged 1-4 years and soft tissue sarcoma (STS) aged 0-14 years (p = 0.0041). Findings from this study are consistent with possible common aetiological factors between different diagnostic groups. They suggest a common aetiology for the following pairs of diagnostic groups: HL and IIET; older cases of LL and HL; younger cases of LL and STS. The possibility of common infectious mechanisms should be explored.

No rise in incidence but geographical heterogeneity in the occurrence of primary biliary cirrhosis in North East England.

In this study, we examined temporal changes in the incidence of primary biliary cirrhosis (PBC) and investigated associations between PBC incidence and sociodemographic factors and spatial clustering. We included 982 patients aged ≥40 years from North East England with incident PBC diagnosed during 1987-2003. Age-standardized incidence rates with 95% confidence intervals were calculated. Negative binomial regression was used to analyze incidence and socioeconomic deprivation. Clustering analysis was performed using point process methods, testing the null hypothesis that disease risk does not vary spatially and that PBC cases occur independently. The age-standardized incidence rate was 53.50 per million persons per year (95% confidence interval: 48.65, 58.35) in 1987-1994 and 45.09 per million persons per year (95% confidence interval: 41.10, 49.07) in 1995-2003. Risk of PBC increased in areas with higher levels of socioeconomic deprivation (P = 0.035). More specifically, risk increased in areas with higher levels of overcrowded homes (P = 0.040), higher levels of households without cars (P < 0.001), and higher levels of non-owner-occupied homes (P < 0.001). Overall, there was evidence of spatial clustering (P = 0.001). The findings confirm that overall incidence of PBC did not rise over time, but sociodemographic variations suggest that certain aspects of deprivation are involved in its etiology.

Evaluation of treatment outcome in 175 patients with Hodgkin lymphoma aged 60 years or over: the SHIELD study.

The SHIELD program for Hodgkin lymphoma in patients 60 years of age or older, prospectively evaluated clinical features and outcome in a large patient cohort (n = 175). The central element was a phase 2 study of VEPEMB chemotherapy (n = 103, median age 73 years) incorporating comorbidity assessment. A total of 72 other patients were treated off-study but registered prospectively and treated concurrently with: ABVD (n = 35); CLVPP (n = 19), or other (n = 18). Of VEPEMB patients, 31 had early-stage disease (stage 1A/2A) and received VEPEMB 3 times plus radiotherapy. Median follow-up was 36 months. Complete remission (CR) rate (intention-to-treat) was 74% and 3-year overall survival (OS) and progression-free survival (PFS) were 81% and 74%, respectively. A total of 72 patients had advanced-stage disease (stage 1B/2B/3 or 4) and received VEPEMB 6 times. CR rate was 61% with 3-year OS and PFS of 66% and 58%, respectively. Of patients achieving CR, 13% with early-stage and 5% with advanced-stage disease progressed. Overall treatment-related mortality was 7%. In patients treated with curative intent with VEPEMB, ABVD, and CLVPP (n = 157), CR linked to several factors in univariate analysis. In a Cox regression model only, obtaining CR remained significant for OS and CR plus comorbidity and age for PFS. RS-EBV status had no significant effect on outcome.

Colonoscopic factors associated with adenoma detection in a national colorectal cancer screening program.

BACKGROUND AND STUDY AIMS: Adenoma detection is a key objective of colonoscopy, particularly in the context of colorectal cancer screening. The aim of this observational study was to identify the technical colonoscopy factors associated with adenoma detection. PATIENTS AND METHODS: The study analyzed data from the English Bowel Cancer Screening Programme. The indication for all colonoscopies was a positive fecal occult blood test. The relationships between the following colonoscopy factors and adenoma detection (one or more adenomas, advanced adenomas, right-sided adenomas, and total number of adenomas) were examined in multivariable analyses: bowel preparation quality, cecal intubation, withdrawal time, rectal retroversion, colonoscopist experience, antispasmodic use, sedation use, and start time of procedure. The following patient factors were controlled for: age, sex, body mass index, smoking, alcohol, deprivation, and geographical location. RESULTS: A total of 31088 colonoscopies were analyzed. The following technical factors increased the relative risk of adenoma detection (P < 0.001 in multivariable analysis unless otherwise stated): cecal intubation, increased withdrawal time, higher quality bowel preparation, intravenous antispasmodic use, earlier procedure start time within a session (P = 0.018), and greater colonoscopist experience. Detection of advanced and right-sided adenomas also increased with these factors. Adenoma detection did not differ between sedated and unsedated colonoscopy (P = 0.143). CONCLUSION: This study demonstrated important associations between colonoscopy practice and adenoma detection. Use of intravenous antispasmodic was associated with increased adenoma detection. The effect of the start time of colonoscopy suggests that endoscopist fatigue may have a deleterious impact on adenoma detection.

Lack of Association of Vascular Risk Factors with HIV-Associated Neurocognitive Disorders in cART-Treated Adults Aged ≥ 50 Years in Tanzania.

HIV-associated neurocognitive disorders (HAND) are highly prevalent in those ageing with HIV. High-income country data suggest that vascular risk factors (VRFs) may be stronger predictors of HAND than HIV-disease severity, but data from sub-Saharan Africa are lacking. We evaluated relationships of VRFs, vascular end-organ damage and HAND in individuals aged ≥ 50 in Tanzania. c-ART-treated individuals were assessed for HAND using consensus criteria. The prevalence of VRFs and end organ damage markers were measured. The independent associations of VRFs, end organ damage and HAND were examined using multivariable logistic regression. Data were available for 153 individuals (median age 56, 67.3% female). HAND was highly prevalent (66.7%, 25.5% symptomatic) despite well-managed HIV (70.5% virally suppressed). Vascular risk factors included hypertension (34%), obesity (10.5%), hypercholesterolemia (33.3%), diabetes (5.3%) and current smoking (4.6%). End organ damage prevalence ranged from 1.3% (prior myocardial infarction) to 12.5% (left ventricular hypertrophy). Measured VRFs and end organ damage were not independently associated with HAND. The only significant association was lower diastolic BP (p 0.030, OR 0.969 (0.943-0.997). Our results suggest that vascular risk factors are not major drivers of HAND in this setting. Further studies should explore alternative aetiologies such as chronic inflammation.

Evidence of spatial clustering of childhood acute lymphoblastic leukemia cases in Greater Mexico City: report from the Mexican Inter-Institutional Group for the identification of the causes of childhood leukemia.

Background: A heterogeneous geographic distribution of childhood acute lymphoblastic leukemia (ALL) cases has been described, possibly, related to the presence of different environmental factors. The aim of the present study was to explore the geographical distribution of childhood ALL cases in Greater Mexico City (GMC). Methods: A population-based case-control study was conducted. Children <18 years old, newly diagnosed with ALL and residents of GMC were included. Controls were patients without leukemia recruited from second-level public hospitals, frequency-matched by sex, age, and health institution with the cases. The residence address where the patients lived during the last year before diagnosis (cases) or the interview (controls) was used for geolocation. Kulldorff's spatial scan statistic was used to detect spatial clusters (SCs). Relative risks (RR), associated p-value and number of cases included for each cluster were obtained. Results: A total of 1054 cases with ALL were analyzed. Of these, 408 (38.7%) were distributed across eight SCs detected. A relative risk of 1.61 (p<0.0001) was observed for the main cluster. Similar results were noted for the remaining seven ones. Additionally, a proximity between SCs, electrical installations and petrochemical facilities was observed. Conclusions: The identification of SCs in certain regions of GMC suggest the possible role of environmental factors in the etiology of childhood ALL.

Colonoscopy quality measures: experience from the NHS Bowel Cancer Screening Programme.

OBJECTIVES: Colonoscopy is central to colorectal cancer (CRC) screening. Success of CRC screening is dependent on colonoscopy quality. The NHS Bowel Cancer Screening Programme (BCSP) offers biennial faecal occult blood (FOB) testing to 60-74 year olds and colonoscopy to those with positive FOB tests. All colonoscopists in the screening programme are required to meet predetermined standards before starting screening and are subject to ongoing quality assurance. In this study, the authors examine the quality of colonoscopy in the NHS BCSP and describe new and established measures to assess and maintain quality. DESIGN: The NHS BCSP database collects detailed data on all screening colonoscopies. Prospectively collected data from the first 3 years of the programme (August 2006 to August 2009) were analysed. Colonoscopy quality indicators (adenoma detection rate (ADR), polyp detection rate, colonoscopy withdrawal time, caecal intubation rate, rectal retroversion rate, polyp retrieval rate, mean sedation doses, patient comfort scores, bowel preparation quality and adverse event incidence) were calculated along with measures of total adenoma detection. RESULTS: 2,269,983 individuals returned FOB tests leading to 36,460 colonoscopies. Mean unadjusted caecal intubation rate was 95.2%, and mean withdrawal time for normal procedures was 9.2 min. The mean ADR per colonoscopist was 46.5%. The mean number of adenomas per procedure (MAP) was 0.91; the mean number of adenomas per positive procedure (MAP+) was 1.94. Perforation occurred after 0.09% of procedures. There were no procedure-related deaths. CONCLUSIONS: The NHS BCSP provides high-quality colonoscopy, as demonstrated by high caecal intubation rate, ADR and comfort scores, and low adverse event rates. Quality is achieved by ensuring BCSP colonoscopists meet a high standard before starting screening and through ongoing quality assurance. Measuring total adenoma detection (MAP and MAP+) as adjuncts to ADR may further enhance quality assurance.

Type 1 diabetes in North East England and North Cumbria: patterns and time trends in 0-14-year-olds from 2012 to 2020.

Introduction: It is important to understand patterns in the epidemiology of type 1 diabetes because they may provide insight into its etiology. We examined the incidence of type 1 diabetes in children aged 0-14 years, and patient demographics and clinical parameters at presentation, over the period 2012-2020 using the North East and North Cumbria Young Persons diabetes register. Methods: Patients up to the age of 14 years with type 1 diabetes, and their families- managed in a total of 18 young persons diabetes clinics-were approached in person at the time of clinic appointments or in the days following diagnosis and they consented to their data being included in the register. Data were submitted regionally to a central unit. Descriptive statistics including crude and age-specific incidence rates were calculated. Temporal trends were analyzed using Joinpoint regression. Comparisons in incidence rates were made between age, sex and areas of higher and lower affluence as measured by the Index of Multiple Deprivation (IMD). Results: A total of 943 cases were recorded between January 2012 and December 2020. Median age at diagnosis was 8.8 years (Q1: 5.3, Q3: 11.7). There were more males than females (54% male). The median HbA1c at diagnosis was 100 mmoL/L (IQR: 39) and over one third (35%) were in ketoacidosis (pH < 7.3). Crude incidence decreased from 25.5 (95% confidence interval [CI] 20.9, 29.9) in 2012 to 16.6 (95% CI: 13.0, 20.2) per 100,000 in 2020 (5.1% per annum, 95% CI 1.1, 8.8%). During the period of the study there was no evidence of any trends in median age, HbA1c, BMI or birthweight (p = 0.18, 0.80, 0.69, 0.32) at diagnosis. Higher rates were observed in males aged 10-14 years, but similar rates were found for both sexes aged 0-9 years and there was no difference between areas of higher or lower deprivation (p = 0.22). Conclusion: The incidence of diabetes in the young may be falling in the North East of England and North Cumbria. The reasons are unclear as there were no associations identified between levels of deprivation or anthropometric measurements. Potential mechanisms include alterations in socioeconomic background or growth pattern. Further research is needed to understand the reasons behind this finding.

Seasonal variation in the patient diagnosis of primary biliary cirrhosis: further evidence for an environmental component to etiology.

UNLABELLED: The etiology of primary biliary cirrhosis (PBC) is far from clear. Both genetic and environmental factors are likely to be involved. We have previously reported evidence of space-time clustering, suggesting that a transient environmental agent may be involved in etiology. To further examine whether a seasonally varying environmental agent may contribute to the etiology of PBC, we have analyzed seasonal variation with respect to month of diagnosis using population-based data from northeast England over a defined period (1987-2003). Date of diagnosis was defined as the earliest date at which the patient was found to have fulfilled any two of three diagnostic criteria (i.e., antimitochondrial antibody-positive titer ≥1 in 40, cholestatic liver blood tests, diagnostic or compatible liver histology). Monthly expected (E) numbers of cases were calculated under an assumption of a uniform distribution throughout the year. Observed counts (O) were compared with the expected numbers. The chi-squared heterogeneity test was used to test for overall nonuniform variation and also for individual months. Poisson regression analysis was used to fit a sinusoidal (i.e., harmonic) model to the data, using month of diagnosis as a covariate in the model. There was a marked peak for diagnoses in the month of June (O = 115, E = 84.7, O/E = 1.36; P = 0.001). Furthermore, there was evidence of a sinusoidal pattern with a June peak (P = 0.012). CONCLUSION: These highly novel results provide further evidence for the involvement of a seasonally varying environmental agent in the etiology of PBC.