Real-world implementation of non-endoscopic triage testing for Barrett's oesophagus during COVID-19.

BACKGROUND: The Coronavirus pandemic (COVID-19) curtailed endoscopy services, adding to diagnostic backlogs. Building on trial evidence for a non-endoscopic oesophageal cell collection device coupled with biomarkers (Cytosponge), an implementation pilot was launched for patients on waiting lists for reflux and Barrett's oesophagus surveillance. AIMS: (i) To review reflux referral patterns and Barrett's surveillance practices. (ii) To evaluate the range of Cytosponge findings and impact on endoscopy services. DESIGN AND METHODS: Cytosponge data from centralized laboratory processing (trefoil factor 3 (TFF3) for intestinal metaplasia (IM), haematoxylin & eosin for cellular atypia and p53 for dysplasia) over a 2-year period were included. RESULTS: A total of 10 577 procedures were performed in 61 hospitals in England and Scotland, of which 92.5% (N = 9784/10 577) were sufficient for analysis. In the reflux cohort (N = 4074 with gastro-oesophageal junction sampling), 14.7% had one or more positive biomarkers (TFF3: 13.6% (N = 550/4056), p53: 0.5% (21/3974), atypia: 1.5% (N = 63/4071)), requiring endoscopy. Among samples from individuals undergoing Barrett's surveillance (N = 5710 with sufficient gland groups), TFF3-positivity increased with segment length (odds ratio = 1.37 per cm (95% confidence interval: 1.33-1.41, P < 0.001)). Some surveillance referrals (21.5%, N = 1175/5471) had ≤1 cm segment length, of which 65.9% (707/1073) were TFF3 negative. Of all surveillance procedures, 8.3% had dysplastic biomarkers (4.0% (N = 225/5630) for p53 and 7.6% (N = 430/5694) for atypia), increasing to 11.8% (N = 420/3552) in TFF3+ cases with confirmed IM and 19.7% (N = 58/294) in ultra-long segments. CONCLUSIONS: Cytosponge-biomarker tests enabled targeting of endoscopy services to higher-risk individuals, whereas those with TFF3 negative ultra-short segments could be reconsidered regarding their Barrett's oesophagus status and surveillance requirements. Long-term follow-up will be important in these cohorts.

Population genetics data help to guide the conservation of palm species with small population sizes and fragmented habitats in Madagascar.

BACKGROUND: The need to incorporate genetic data into conservation management decisions is increasingly recognised. However, many published studies represent a 'gold standard' of sampling, techniques, and analyses. Such rigour is often not possible with limited funding and resourcing available for developing plans for the increasing number of threatened species requiring conservation management. Two endemic palm species of the Itremo Massif in central Madagascar, Dypsis ambositrae and D. decipiens, are known to be threatened with extinction and conservation management for these species is a priority for the newly created protected area in the region. METHODS: The genetic diversity of these two species was studied using the relatively low-cost and rapid AFLP technique. DNA fragments generated using three primer combinations were analysed for 20 and 50 individuals of the two species, respectively, from across their ranges. RESULTS: Genetic diversity was relatively low for both species. The two sites where the highly restricted D. ambositrae grows were found to be genetically distinct (although overall heterozygosity was low). Despite having a much wider distribution and relatively large population, D. decipiens did not show clear geographical nor genetic groupings and had similarly low genetic heterozygosity to D. ambositrae. DISCUSSION AND RECOMMENDATIONS: With so few individuals remaining in the wild and two genetically distinct subpopulations, it is recommended that both sites of D. ambositrae are conserved and that seed are collected from both for ex situ conservation and potential future reintroduction. It may be less important to focus resources on conserving or collecting ex situ material from all sites where D. decipiens is found, as the genetic diversity represented by each subpopulation is limited and increasing sampling may not protect significantly higher levels of genetic diversity. This study provides data that inform and support conservation decisions taken for both species within this region, and in the management of the newly designated Itremo Massif Protected Area, which covers most of the sites where these two species remain in the wild.

Are IQ and educational outcomes in teenagers related to their cannabis use? A prospective cohort study.

There is much debate about the impact of adolescent cannabis use on intellectual and educational outcomes. We investigated associations between adolescent cannabis use and IQ and educational attainment in a sample of 2235 teenagers from the Avon Longitudinal Study of Parents and Children. By the age of 15, 24% reported having tried cannabis at least once. A series of nested linear regressions was employed, adjusted hierarchically by pre-exposure ability and potential confounds (e.g. cigarette and alcohol use, childhood mental-health symptoms and behavioural problems), to test the relationships between cumulative cannabis use and IQ at the age of 15 and educational performance at the age of 16. After full adjustment, those who had used cannabis ⩾ 50 times did not differ from never-users on either IQ or educational performance. Adjusting for group differences in cigarette smoking dramatically attenuated the associations between cannabis use and both outcomes, and further analyses demonstrated robust associations between cigarette use and educational outcomes, even with cannabis users excluded. These findings suggest that adolescent cannabis use is not associated with IQ or educational performance once adjustment is made for potential confounds, in particular adolescent cigarette use. Modest cannabis use in teenagers may have less cognitive impact than epidemiological surveys of older cohorts have previously suggested.

Evaluating cytology for the detection of invasive cervical cancer.

OBJECTIVE: To assess the sensitivity, the number needed to screen (NNS) and the positive predictive value (PPV) of cervical cytology for the diagnosis of cancer by age in a screening population. METHODS: A retrospective cohort of women with invasive cervical cancer nested within a census of cervical cytology. All (c. 8 million) women aged 20-64 years with cervical cytology (excluding tests after an earlier abnormality). From April 2007 to March 2010, 3372 women had cervical cancer diagnosed within 12 months of such cytology in England. The sensitivity of cervical cytology to cancer, NNS to detect one cancer and predictive values of cytology were calculated for various 'referral' thresholds. These were calculated for ages 20-24, 25-34, 35-49 and 50-64 years. RESULTS: The sensitivity of at least moderate dyskaryosis [equivalent to a high-grade squamous intraepithelial lesion (HSIL) or worse] for cancer of 89.4% [95% confidence interval (CI) 88.3-90.4%] in women offered screening was independent of age. At all ages, women with borderline-early recall or mild dyskaryosis on cytology (equivalent to ASC-US and LSIL, respectively, in the Bethesda system) had a similar risk of cervical cancer to the risk in all women tested. The PPV of severe dyskaryosis/?invasive and ?glandular neoplasia cytology (equivalent to squamous cell carcinoma and adenocarcinoma/adenocarcinoma in situ, respectively, in the Bethesda System) were 34% and 12%, respectively; the PPV of severe dyskaryosis (HSIL: severe dysplasia) was 4%. The NNS was lowest when the incidence of cervical cancer was highest, at ages 25-39 years, but the proportion of those with abnormal cytology who have cancer was also lowest in younger women. CONCLUSIONS: The PPV of at least severe dyskaryosis (HSIL: severe dysplasia) for cancer was 4-10% of women aged 25-64 years, justifying a 2-week referral to colposcopy and demonstrating the importance of failsafe monitoring for such patients. The sensitivity of cytology for cervical cancer was excellent across all age groups.

How many preterm births in England are due to excision of the cervical transformation zone? Nested case control study.

BACKGROUND: Preterm births (as a proportion of all births) have been increasing in many countries. There is growing evidence of increased risk of preterm birth following excisional treatment of the cervix. We estimate the number of preterm births attributable to excisional treatments with a length of 10 mm or more in England. METHODS: Case-control study nested in a record linkage cohort of women with a histological sample at 13 hospitals in England. We combined observed age at first excisional treatment in our cohort with the weighted distribution of excision length from the case-control study to estimate the length distribution by age at first treatment among the cohort. The number of births after excision for each 5-year age group was estimated using national fertility data; published absolute risks of preterm (<37 gestational weeks) and very preterm birth (<32 weeks) were applied to these to estimate the number of preterm births per 100 women treated. Excess preterm births were estimated assuming all treatments were small. The attributable risk of preterm birth following excisional treatment in England was estimated. RESULTS: The majority of first excisional treatments at colposcopy were small (47.5%) or medium (39.1%), 9.5% were large and 4.1% were very large excisions. 4.0% of women treated before birth had more than one excisional treatment. Thus based on our cohort of 10,711 treated women and the length of treatment observed in the case control study we estimate an excess of 240 preterm births (including 57 very preterm) or 2.2 (including 0.5 very preterm) per 100 women treated. At a population level (for England) we estimate that 39,101 women aged 20-39 would be treated each year and that these treatments will lead to an excess of 840 preterm births (including 196 very preterm) in England each year. CONCLUSIONS: Assuming associations between preterm birth and treatment for cervical disease are causal; we estimate that an excess 840 (2.5%) preterm birth in England each year are due to excisional treatments of 10 mm or more. Those that go on to become pregnant should be closely monitored during antenatal period to reduce their risk of preterm birth.

Is the increased risk of preterm birth following excision for cervical intraepithelial neoplasia restricted to the first birth post treatment?

OBJECTIVE: To explore whether the increased risk of preterm birth following treatment for cervical disease is limited to the first birth following colposcopy. DESIGN: Nested case-control study. SETTING: Twelve NHS hospitals in England. POPULATION: All nonmultiple births from women selected as cases or controls from a cohort of women with both colposcopy and a hospital birth. Cases had a preterm (20-36 weeks of gestation) birth. Controls had a term birth (38-42 weeks) and no preterm. METHODS: Obstetric, colposcopy and pathology details were obtained. MAIN OUTCOME MEASURES: Adjusted odds ratio of preterm birth in first and second or subsequent births following treatment for cervical disease. RESULTS: A total of 2798 births (1021 preterm) from 2001 women were included in the analysis. The risk of preterm birth increased with increasing depth of treatment among first births post treatment [trend per category increase in depth, categories <10 mm, 10-14 mm, 15-19 mm, ≥20 mm: odds ratio (OR) 1.23, 95% confidence interval (95% CI) 1.12-1.36, P < 0.001] and among second and subsequent births post treatment (trend OR 1.34, 95% CI 1.15-1.56, P < 0.001). No trend was observed among births before colposcopy (OR 0.98, 95% CI 0.83-1.16, P = 0.855). The absolute risk of a preterm birth following deep treatments (≥15 mm) was 6.5% among births before colposcopy, 18.9% among first births and 17.2% among second and subsequent births post treatment. Risk of preterm birth (once depth was accounted for) did not differ when comparing first births post colposcopy with second and subsequent births post colposcopy (adjusted OR 1.15, 95% CI 0.89-1.49). CONCLUSIONS: The increased risk of preterm birth following treatment for cervical disease is not restricted to the first birth post colposcopy; it remains for second and subsequent births. These results suggest that once a woman has a deep treatment she remains at higher risk of a preterm birth throughout her reproductive life.

Benefits and harms of cervical screening from age 20 years compared with screening from age 25 years.

BACKGROUND: To quantify the benefits (cancer prevention and down-staging) and harms (recall and excess treatment) of cervical screening starting from age 20 years rather than from age 25 years. METHODS: We use routine screening and cancer incidence statistics from Wales (for screening from age 20 years) and England (screening from 25 years), and unpublished data from the National Audit of Invasive Cervical Cancer to estimate the number of: screening tests, women with abnormal results, referrals to colposcopy, women treated, and diagnoses of micro-invasive (stage 1A) and frank-invasive (stage IB+) cervical cancers (under three different scenarios) in women invited for screening from age 20 years and from 25 years. RESULTS: Inviting 100,000 women from age 20 years yields an additional: 119,000 screens, 20,000 non-negative results, 8000 colposcopy referrals, and an extra 3000 women treated when compared with inviting from age 25 years. Screening from age 20 years prevents between three and nine frank invasive cancers and between 0 and 23 cancers in total (depending on the scenario). A cumulative increase of nine stage IB+ cancers corresponds to an annual rate increase of 0.9 per 100,000 women aged 20-29 years. CONCLUSIONS: To prevent one frank invasive cancer, one would need to do between 12,500 and 40,000 additional screening tests in the age group 20-24 years and treat between 300 and 900 women.

Characteristics and screening history of women diagnosed with cervical cancer aged 20-29 years.

BACKGROUND: There was concern that failure to screen women aged 20-24 years would increase the number of cancers or advanced cancers in women aged 20-29 years. We describe the characteristics of women diagnosed with cervical cancer in England aged 20-29 years and examine the association between the period of diagnosis, screening history and FIGO stage. METHODS: We used data on 1800 women diagnosed with cervical cancer between April 2007 and March 2012 at age 20-29 from the National Audit of Invasive Cervical Cancers. RESULTS: The majority of cancers (995, or 62% of those with known stage) were stage 1A. Cancer at age 20-24 years was rare (12% of those aged 20-29 years), when compared with age 25 (24%) and age 26-29 years (63%); however, cancers in women aged 20-24 years tended to be more advanced and were more often of a rare histological type. For 59% of women under age 30, the cervical cancer was screen detected, most of them (61%) as a result of their first screening test. A three-fold increase in the number of cancers diagnosed at age 25 years was seen since the start of the study period. CONCLUSION: Cervical cancer at age 20-24 years is rare. Most cancers in women under age 30 years are screen detected as microinvasive cancer.

HLA-dependent autoantibodies against post-translationally modified collagen type II in type 1 diabetes mellitus.

AIMS/HYPOTHESIS: In this study the involvement of oxidative stress in type 1 diabetes mellitus autoimmunity and the possible association with rheumatoid arthritis (RA) was investigated. We tested the hypothesis that oxidative stress induced by chronic hyperglycaemia triggers post-translational modifications and thus the formation of neo-antigens in type 1 diabetes, similar to the ones found in RA. METHODS: Collagen type II (CII), a known autoantigen in RA, was treated with ribose and various reactive oxygen species (ROS). Levels of antibodies specific to native and ROS-modified CII (ROS-CII) were compared in type 1 diabetes, type 2 diabetes and healthy controls, and related to the HLA genotype. RESULTS: Significantly higher binding to ROS-CII vs native CII was observed in type 1 diabetic patients possessing the HLA-DRB1*04 allele irrespective of variables of glucose control (blood glucose or HbA(1c)). Type 1 diabetic patients carrying a DRB1*04 allele with the shared epitope showed the highest risk for ROS-CII autoimmunity, while the DRB1*0301 allele was protective. Conversely, native CII autoimmunity was not associated with any specific DRB1 allele. Positive and inverse seroconversion rates of response to ROS-CII were high in DRB1*04-positive type 1 diabetic patients. CONCLUSION: Hyperglycaemia and oxidative stress may trigger genetically controlled autoimmunity to ROS-CII and may explain the association between type 1 diabetes mellitus and RA.

Regulatory approaches for controlling pesticide residues in food animals.

Pesticide use is vital to the production of an economical, high-quality food supply throughout the world. The regulatory system in the United States is designed to prevent the entry of unacceptable residues into the food supply. To address the complexities associated with pesticide use, the regulatory apparatus is composed of several federal and numerous state agencies. Based on monitoring results, it appears that most pesticides are being used in the appropriate manner and that thresholds for pesticides, deemed to be adequate to protect human health, are seldom exceeded. With our increasing knowledge of the public health and ecologic threats posed by pesticide residues, our approach to regulating pesticides will continue to evolve.

The histiocytoid hemangiomas. A unifying concept embracing several previously described entities of skin, soft tissue, large vessels, bone, and heart.

The proposal is made that a number of previously described entities of skin, soft tissue, large vessels, bone, and heart actually constitute different manifestations of the same basic process, characterized by the proliferation of a highly distinctive type of cell descriptively identified as a "histiocytoid endothelial cell." The entities in question are angiolymphoid hyperplasia with eosinophilia and related cutaneous and subcutaneous disorders, atypical vascular proliferation of large vessels, hemangioendothelioma of bone, and endocardial benign angioreticuloma of the heart. The main cell that proliferates in all these conditions has the basic features of an endothelial cell, but also exhibits histochemical and ultrastructural characteristics that are more akin to those of a histiocyte. These unusual features could be the expression of a morphologic abnormality or represent an overgrowth of a specific and as yet undefined subpopulation of endothelial cells, such as Majno's "contractile endothelial cell." Whether this group of proliferative diseases is of a reactive or a neoplastic nature is not immediately apparent, although the latter seems more likely. However, it is clear that the behavior of these lesions, as a group, is quite indolent and even self-limited, in contrast to the aggressive behavior and often fatal outcome of the true angiosarcomas that they so closely resemble on microscopic grounds. The term "histiocytoid hemangioma" is suggested for this group of disorders.