Trends in work-related respiratory diseases attributed to nickel, chromium and cobalt in the UK: descriptive findings from The Health and Occupation Research (THOR) network 1996-2019.

BACKGROUND: Occupational exposure to metals can be associated with respiratory diseases which can adversely affect the individual's health, finances and employment. Despite this, little is known about the incidence of these respiratory conditions over prolonged periods of time. AIMS: This study aimed to investigate the trends in the incidence of work-related respiratory diseases attributed to nickel, chromium and cobalt in the UK. METHODS: Cases of occupational respiratory diseases caused by nickel, chromium or cobalt reported to Surveillance of Work-related and Occupational Respiratory Disease (SWORD), the UK-based surveillance scheme between 1996 and 2019 (inclusive), were extracted and grouped into six 4-year time periods. Cases were characterised by causative metal exposure, occupational and industrial sector. Incidence rates diseases (adjusted for physician participation and response rate) were calculated using ONS employment data. RESULTS: Of cases reported to SWORD during the study period, 1% (173 actual cases) of respiratory problems were attributed to nickel, chromium or cobalt. Diagnoses of asthma compromised the largest proportion of diagnoses (74.4%), followed by lung cancer (8.9%) and pneumoconiosis (6.7%). Cases had a mean age of 47 years (SD 13); 93% were men. The annual incidence fell from 1.6 per million employed in the first 4-year period, to 0.2 in the most recent period. CONCLUSIONS: Over 24 years, a decline in the incidence of metal-related occupational respiratory diseases was observed in the UK. This could be attributed to improvements in working conditions which resulted in reduced metal exposure but could also be due to closure of industries that might have generated case returns.

Trends in occupational and work-related contact dermatitis attributed to nickel, chromium and cobalt in the UK: findings from The Health and Occupation Research network 1996-2019.

BACKGROUND: Occupational exposure to metals such as nickel, chromium and cobalt can be associated with contact dermatitis, which can adversely affect an individual's health, finances and employment. Despite this, little is known about the incidence of metal-related occupational contact dermatitis over prolonged periods of time. OBJECTIVES: To investigate the medically reported trends in the incidence of work-related contact dermatitis attributed to nickel, chromium and cobalt in the UK. METHODS: Incidence and trends in cases of occupational contact dermatitis caused by nickel, chromium or cobalt between 1996 and 2019 (inclusive), reported to the EPIDERM surveillance scheme, were investigated and compared with trends in the incidence of occupational contact dermatitis attributed to agents other than the aforementioned metals. A sensitivity analysis restricting the study cohort to cases attributed to only one type of metal was also conducted. RESULTS: Of all cases reported to EPIDERM during the study period, 2374 (12%) were attributed to nickel, chromium or cobalt. Cases predominantly comprised females (59%), with a mean (SD) age (males and females) of 38 (13) years. Cases were most frequently reported in manufacturing, construction, and human health and social activity industries. The most frequently reported occupations were hairdressing, and sales and retail (assistants, cashiers and checkout operators). The highest annual incidence rate of contact dermatitis was observed in females (2.60 per 100 000 persons employed per year), with the first and second peak seen in those aged 16-24 and ≥ 65 years, respectively. A statistically significant decrease in the incidence of occupational contact dermatitis attributed to metals over the study period was observed for all occupations (annual average change -6.9%, 95% confidence interval -7.8 to -5.9), with much of the decrease occurring between 1996 and 2007. Similar findings were obtained in the sensitivity analyses. CONCLUSIONS: Over a period of 24 years, there has been a statistically significant decline in the incidence of metal-related occupational contact dermatitis in the UK. This could be attributed not only to improvements in working conditions, which have reduced metal exposure, but could also be due to the closure of industries in the UK that might have generated cases of contact dermatitis owing to metal exposure.

An Epidemiological Study of Lung Cancer and Selected Other Cancers among Namibian Uranium Workers.

The Rössing Uranium Limited (RUL) open-cast uranium mine in Namibia has operated since 1976. Studies of underground uranium miners from Europe and North America have shown increased cancer risks (principally lung cancer). We explored the association between radiation doses and selected cancers in RUL mineworkers. Employees with at least one-year of continuous employment between 1976 and 2010 were included. Incident cancer cases [lung, extra-thoracic airways (ETA), leukemia, brain and kidney] occurring before the end of 2015 were identified from the Namibian and South African National Cancer Registries, and RUL's occupational health provider. Using a case-cohort design, data on exposure and confounding factors were collected for all cancer cases among the study cohort and a stratified random sample (sub-cohort) of the cohort, including cases. Radiation doses were estimated based on annual dose records held by RUL. In total, 76 cancer cases (32 lung, 18 ETA, 8 leukemia, 9 brain, 9 kidney) and a sub-cohort of 1,121 sampled from 7,901 RUL employees were included. A weighted Cox model, adjusted for available known confounders, produced a rate ratio (95% CI) for lung cancer of 1.42 (0.42, 4.77) and 1.22 (0.26, 5.68), respectively, for medium and higher cumulative lung dose categories compared to the lower category, and 1.04 (0.95, 1.13) for a dose increase of 10 mSv. This study faced considerable challenges with respect to case ascertainment, exposure estimates, and ensuring accuracy of key variables. Persuasive consistent evidence for elevated cancer risk was not found for radiation or other exposures studied at the Rössing uranium mine.

Growth of twins conceived using assisted reproductive treatments up to 5 years old: a national growth cohort.

STUDY QUESTION: Do twins conceived through assisted reproductive treatments (ART) grow differently from naturally conceived (NC) twins in early life? SUMMARY ANSWER: Assessments at 6-8 weeks old and at school entry show that ART twins conceived from frozen embryo transfer (FET) grow faster than both NC twins and ART twins conceived from fresh embryo transfer (ET). WHAT IS KNOWN ALREADY: Singletons born from fresh ET grow more slowly in utero and in the first few weeks of life but then show postnatal catch-up growth by school age, compared to NC and FET babies. Evidence on early child growth of ART twins relative to NC twins is inconsistent; most studies are small and do not distinguish FET from fresh ET cycles. STUDY DESIGN, SIZE, DURATION: This cohort study included 13 528 live-born twin babies conceived by ART (fresh ET: 2792, FET: 556) and NC (10 180) between 1991 and 2009 in Scotland. The data were obtained by linking Human Fertilisation and Embryology Authority ART register data to the Scottish Morbidity Record (SMR02) and Scottish child health programme datasets. Outcome data were collected at birth, 6-8 weeks (first assessment), and school entry (4-7 years old) assessments. The primary outcome was growth, measured by weight at the three assessment points. Secondary outcomes were length (at birth and 6-8 weeks) or height (at school entry), BMI, occipital circumference, gestational age at birth, newborn intensive care unit admission, and growth rates (between birth and 6-8 weeks and between 6-8 weeks and school entry). PARTICIPANTS/MATERIALS, SETTING, METHODS: All twins in the linked dataset (born between 1991 and 2009) with growth data were included in the analysis. To determine outcome differences between fresh ET, FET, and NC twins, linear mixed models (or analogous logistic regression models) were used to explore the outcomes of interest. All models were adjusted for available confounders: gestational age/child age, gender, maternal age and smoking, Scottish Index of Multiple Deprivation, year of treatment, parity, ICSI, and ET stage. MAIN RESULTS AND THE ROLE OF CHANCE: In the primary birth weight models, the average birth weight of fresh ET twins was lower [-35 g; 95% CI: (-53, -16)g] than NC controls, while FET twins were heavier [71 g; 95% CI (33, 110) g] than NC controls and heavier [106 g; 95% CI (65, 146) g] than fresh ET twins. However, the difference between FET and NC twins was not significant when considering only full-term twins (≥37 weeks gestation) [26 g; 95% CI (-30, 82) g], while it was significantly higher in preterm twins [126 g; 95% CI (73, 179) g]. Growth rates did not differ significantly for the three groups from birth to 6-8 weeks. However, FET twins grew significantly faster from 6 to 8 weeks than NC (by 2.2 g/week) and fresh ET twins (by 2.1 g/week). By school entry, FET twins were 614 g [95% CI (158, 1070) g] and 581 g [95% CI (100, 1063) g] heavier than NC and fresh ET twins, respectively. Length/height and occipital frontal circumference did not differ significantly at any time point. LIMITATIONS, REASONS FOR CAUTION: Although the differences between ART and NC reflect the true ART effects, these effects are likely to be mediated partly through the different prevalence of mono/dizygotic twins in the two groups. We could not explore the mediating effect of zygosity due to the unavailability of data. The confounding variables included in the study were limited to those available in the datasets. WIDER IMPLICATIONS OF THE FINDINGS: Live-born twins from FET cycles are heavier at birth, grow faster than their fresh ET and NC counterparts, and are still heavier at school entry. This differs from that observed in singletons from the same cohort, where babies in the three conception groups had similar weights by school entry age. The results are reassuring on known differences in FET versus fresh ET and NC twin outcomes. However, FET twins grow faster and are consistently larger, and more ART twins depict catch-up growth. These may lead to an increased risk profile for non-communicable diseases in later life. As such, these twin outcomes require careful evaluation using more recent and comprehensive cohorts. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the EU H2020 Marie Sklodowska-Curie Innovative Training Networks (ITN) grant Dohartnet (H2020-MSCA-ITN-2018-812660). The authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: N/A.

Cerebral and tumoral blood flow in adult gliomas: a systematic review of results from magnetic resonance imaging.

OBJECTIVE: Blood flow is the rate of blood movement and relevant to numerous processes, though understudied in gliomas. The aim of this review was to pool blood flow metrics obtained from MRI modalities in adult supratentorial gliomas. METHODS: MEDLINE, EMBASE and the Cochrane database were queried 01/01/2000-31/12/2019. Studies measuring blood flow in adult Grade II-IV supratentorial gliomas using dynamic susceptibility contrast (DSC) MRI, dynamic contrast enhanced MRI (DCE-MRI) or arterial spin labelling (ASL) were included. Absolute and relative cerebral blood flow (CBF), peritumoral blood flow and tumoral blood flow (TBF) were reported. RESULTS: 34 studies were included with 1415 patients and 1460 scans. The mean age was 52.4 ± 7.3 years. Most patients had glioblastoma (n = 880, 64.6%). The most common imaging modality was ASL (n = 765, 52.4%) followed by DSC (n = 538, 36.8%). Most studies were performed pre-operatively (n = 1268, 86.8%). With increasing glioma grade (II vs IV), TBF increased (70.8 vs 145.5 ml/100 g/min, p < 0.001) and CBF decreased (85.3 vs 49.6 ml/100 g/min, p < 0.001). In Grade IV gliomas, following treatment, CBF increased in ipsilateral (24.9 ± 1.2 vs 26.1 ± 0.0 ml/100 g/min, p < 0.001) and contralateral white matter (25.6 ± 0.2 vs 26.0± 0.0 ml/100 g/min, p < 0.001). CONCLUSION: Our findings demonstrate that increased mass effect from high-grade gliomas impairs blood flow within the surrounding brain that can improve with surgery. ADVANCES IN KNOWLEDGE: This systematic review demonstrates how mass effect from brain tumours impairs blood flow in the surrounding brain parenchyma that can improve with treatment.

A natural experimental study of improvements along an urban canal: impact on canal usage, physical activity and other wellbeing behaviours.

BACKGROUND: There are few robust natural experimental studies of improving urban green spaces on physical activity and wellbeing. The aim of this controlled natural experimental study was to examine the impact of green space improvements along an urban canal on canal usage, physical activity and two other wellbeing behaviours (social interactions and taking notice of the environment) among adults in Greater Manchester, UK. The intervention included resurfaced footpaths, removal of encroaching vegetation, improved entrances, new benches and signage. METHODS: Two comparison sites were matched to the intervention site using a systematic five-step process, based on eight correlates of physical activity at the neighbourhood (e.g. population density) and site (e.g. lighting) levels. Outcomes were assessed using systematic observations at baseline, and 7, 12 and 24 months post-baseline. The primary outcome was the change in the number of people using the canal path from baseline to 12 months. Other outcomes were changes in physical activity levels (Sedentary, Walking, Vigorous), Connect and Take Notice behaviours. Data were analysed using multilevel mixed-effects negative binomial regression models, comparing outcomes in the intervention group with the matched comparison group, controlling for day, time of day and precipitation. A process evaluation assessed potential displacement of activity from a separate existing canal path using intercept surveys and observations. RESULTS: The total number of people observed using the canal path at the intervention site increased more than the comparison group at 12 months post-baseline (IRR 2.10, 95% CI 1.79-2.48); there were similar observed increases at 7 and 24 months post-baseline. There was some evidence that the intervention brought about increases in walking and vigorous physical activity, social interactions, and people taking notice of the environment. The process evaluation suggested that there was some displacement of activity, but the intervention also encouraged existing users to use the canal more often. CONCLUSIONS: Urban canals are promising settings for interventions to encourage green space usage and potentially increase physical activity and other wellbeing behaviours. Interventions that improve access to green corridors along canals and provide separate routes for different types of physical activities may be particularly effective and warrant further research. STUDY PROTOCOL: Study protocol published in Open Science Framework in July 2018 before the first follow-up data collection finished ( https://osf.io/zcm7v ). Date of registration: 28 June 2018.

PROgesterone Therapy for Endometrial Cancer Prevention in Obese Women (PROTEC) Trial: A Feasibility Study.

Obesity is the major etiologic driver for endometrial cancer. The levonorgestrel intrauterine system (LNG-IUS) reduces the risk of endometrial cancer and its precursor, atypical hyperplasia. We assessed feasibility and uptake of the LNG-IUS for primary prevention of endometrial cancer in high-risk women and its impact on endometrial tissue biomarkers. Women with class-III obesity [body mass index (BMI) > 40 kg/m2] and histologically normal endometrium were invited to participate in a clinical trial of the LNG-IUS for endometrial protection. Recruitment, successful LNG-IUS insertion, and adherence to trial procedures were recorded. We measured impact of the LNG-IUS on circulating biomarkers of endometrial cancer risk, endometrial proliferation (Ki-67, pAKT, PTEN), endometrial hormone receptor status [estrogen receptor and progesterone receptor (PR)], mental wellbeing, and menstrual function. At 6 months, women chose to keep their LNG-IUS or have it removed. In total, 103 women were approached, 54 were offered a participant information sheet, 35 agreed to participate, and 25 received a LNG-IUS. Their median age and BMI were 54 years [interquartile range (IQR) 52-57] and 47 kg/m2 (IQR 44-51), respectively. Three women (3/35, 9%) were ineligible due to atypical hyperplasia/endometrial cancer on their baseline biopsy. The LNG-IUS was well tolerated and had a positive overall effect on bleeding patterns and mental wellbeing. The LNG-IUS was associated with endometrial morphologic change, reduced Ki-67, and PR expression, but circulating biomarkers of endometrial cancer risk were unchanged. All but one woman (96%) kept her LNG-IUS. The LNG-IUS appears to be acceptable to some women with class-III obesity for primary prevention of endometrial cancer, which could provide a strategy for a prevention trial.Prevention Relevance: Novel strategies are urgently needed to prevent the rise in endometrial cancer diagnoses predicted by escalating obesity rates. Here, we show that women with class III obesity are willing to engage in risk reduction with a levonorgestrel intrauterine system, which could provide a strategy for an endometrial cancer prevention trial.

Needs-based quality of life in adults dependent on home parenteral nutrition.

BACKGROUND & AIMS: Home parenteral nutrition (HPN) provides life sustaining treatment for people with chronic intestinal failure. Individuals may require HPN for months or years and are dependent on regular intravenous infusions, usually 12-14 h overnight between 1 and 7 days each week. This regime can have adverse impact on the life of people dependent on the treatment. The aim of this study was to establish mean values for the Parenteral Nutrition Impact Questionnaire (PNIQ) and to determine the effect of disease, frequency of infusions per week and patient characteristics on quality of life of patients fed HPN. METHOD: The PNIQ was distributed to patients across nine UK HPN clinics. Data were analysed using linear regression, with PNIQ score as the dependent variable and potential confounders as independent variables. Unadjusted and adjusted models are presented. Higher PNIQ scores reflect poorer quality of life. RESULTS: Completed questionnaires were received from 466 people dependent on HPN. Mean PNIQ score was 11.04 (SD 5.79). A higher PNIQ score (effect size 0.52, CI 0.184 to 0.853) was recorded in those dependent on a higher frequency of HPN infusions per week. Respondents with cancer had a similar mean PNIQ score to those with inflammatory bowel disease (mean 10.82, SD 6.00 versus 11.04, SD 5.91). Those with surgical complications reported a poorer QoL (effect size 3.03, CI 0.642 to 5.418) and those with severe gastro-intestinal dysmotility reported a better QoL (effect size -3.03, CI -5.593 to -0.468), compared to other disease states. CONCLUSIONS: This large cohort study of quality of life in chronic intestinal failure demonstrates that HPN impacts individuals differently depending on their underlying disease. Furthermore, since the number of HPN infusions required per week is inversely related to an individual's needs-based quality of life, therapies that reduce PN burden should lead to an improvement in QoL.

Cost-effectiveness of strategies to increase cervical screening uptake at first invitation (STRATEGIC).

Objective To assess the cost-effectiveness of strategies to increase cervical cancer screening uptake at first invitation (STRATEGIC trial). Methods We performed an economic analysis alongside the STRATEGIC trial, comparing each of seven novel interventions for improving cervical screening uptake with control general practices in Greater Manchester and Grampian (United Kingdom). A template was developed to measure the intervention costs. Trial estimates of screening uptake were combined with data from the literature to estimate healthcare costs of each intervention. The added lifetime costs and quality adjusted life years (QALYs) of attending cervical screening were estimated by a systematic literature review, with relevant results pooled and weighted by study quality. Trial results and estimated lifetime costs and benefits of screening were then combined in a decision analytic model, giving an incremental cost per QALY gained for each intervention. Uncertainty was addressed in probabilistic and univariate sensitivity analyses. Results Intervention costs per screening round per woman attending varied from about £1.20 (2014 UK) for the nurse navigator intervention to £62 for the unrequested HPV self-sampler kit. The meta-analysis revealed a lifetime discounted benefit from screening of 0.043 QALYs per woman attending, at an additional lifetime discounted cost of £234. The incremental cost per QALY gained in all interventions was below £13,000. Probabilistic sensitivity analyses suggested that only unrequested self-sampling and timed appointments have a high probability of being cost-effective. Conclusions Unrequested self-sampling and timed appointments are likely to be cost-effective interventions. Further research is required on the duration of effects and on implementing combinations of interventions.

Chest physician-reported, work-related, long-latency respiratory disease in Great Britain.

Much of the current burden of long-latency respiratory disease (LLRD) in Great Britain is attributed to historical asbestos exposure. However, continuing exposure to other agents, notably silica, also contributes to disease burden. The aim of this study was to investigate the incidence of work-related LLRD reported by chest physicians in Great Britain, including variations by age, gender, occupation and suspected agent.LLRD incidence and incidence rate ratios by occupation were estimated (1996-2014). Mesothelioma cases by occupation were compared with proportional mortality ratios.Cases were predominantly in men (95%) and 92% of all cases were attributed to asbestos. Annual average incidence rates (males) per 100 000 were: benign pleural disease, 7.1 (95% CI 6.0-8.2); mesothelioma, 5.4 (4.8-6.0); pneumoconiosis, 1.9 (1.7-2.2); lung cancer, 0.8 (0.6-1.0); chronic obstructive pulmonary disease (COPD), 0.3 (0.2-0.4). Occupations with a particularly high incidence of LLRD were miners and quarrymen (COPD), plumbers and gas fitters (asbestosis), and shipyard and dock workers (all other categories). There was a clear concordance between cases of SWORD mesothelioma and proportional mortality ratios by occupation.Occupationally caused LLRD continues to contribute to a significant disease burden. Many cases are attributable to past exposure to agents such as asbestos and silica, but the potential for occupational exposures persists.

A cluster randomised trial of strategies to increase cervical screening uptake at first invitation (STRATEGIC).

BACKGROUND: Falling participation by young women in cervical screening has been observed at a time that has seen an increase in the incidence of cervical cancer in the UK in women aged < 35 years. Various barriers to screening have been documented, including fear, embarrassment and inconvenience. OBJECTIVES: To measure the feasibility, clinical effectiveness and cost-effectiveness of a range of interventions to increase the uptake of cervical screening among young women. DESIGN: A cluster randomised trial based on general practices performed in two phases. SETTING: Primary care in Greater Manchester and the Grampian region in Scotland. PARTICIPANTS: Phase 1: 20,879 women receiving their first invitation for cervical screening. Phase 2: 10,126 women who had not attended by 6 months. INTERVENTIONS: Phase 1: pre-invitation leaflet or not, and access to online booking (Manchester only). Phase 2: (1) vaginal self-sampling kits (SSKs) sent unrequested (n = 1141); or (2) offered on request (n = 1290); (3) provided with a timed appointment (n = 1629); (4) offered access to a nurse navigator (NN) (n = 1007); or (5) offered a choice between a NN or a SSK (n = 1277); and 3782 women in control practices. MAIN OUTCOME MEASURES: Uplift in screening compared with control practices, cost-effectiveness of interventions, and the women's preferences explored in a discrete choice experiment. RESULTS: The pre-invitation leaflet and offer of online booking were ineffective when compared with control practices at 3 months, 18.8% versus 19.2% [odds ratio (OR) 0.96, 95% confidence interval (CI) 0.88 to 1.06; p = 0.485] and 17.8% versus 17.2% (OR 1.02, 95% CI 0.87 to 1.20; p = 0.802), respectively. The uptake of screening at 3 months was higher among previously human papillomavirus (HPV)-vaccinated women than unvaccinated women, 23.7% versus 11% (OR 2.07, 95% CI 1.69 to 2.53; p < 0.001). Among non-attenders, the SSK sent intervention showed a statistically significant increase in uptake at 12 months post invitation, 21.3% versus 16.2% (OR 1.51, 95% CI 1.20 to 1.91; p = 0.001), as did timed appointments, 19.8% versus 16.2% (OR 1.41, 95% CI 1.14 to 1.74; p = 0.001). The offer of a NN, a SSK on request, and a choice between timed appointments and NN were ineffective. Overall, there was a gradual rather than prompt response, as demonstrated by uptake among control practices. A discrete choice experiment indicated that women invited who had not yet attended valued the attributes inherent in self-sampling. The health economic analysis showed that both timed appointments and unsolicited SSK sent were likely to be cost-effective at a cost per quality-adjusted life-year (QALY) gained of £7593 and £8434, respectively, if extended across the national 25-year-old cohort throughout the duration of screening. The certainty of these being cost-effective at a ceiling ratio of £20,000 per QALY gained was > 90%. CONCLUSION: Women receiving their initial screening invitation frequently delay taking up the offer and the net impact of interventions was small. Timed appointments and SSKs sent to non-attenders at 6 months are likely to be a cost-effective means of increasing uptake and should be considered further. HPV vaccination in the catch-up programme was associated with an increased uptake of cervical screening. Future work should focus on optimising self-sampling in terms of age range, timing of offer for non-attenders and use of urine testing instead of vaginal samples. TRIAL REGISTRATION: Current Controlled Trials ISRCTN52303479. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 68. See the NIHR Journals Library website for further project information.

A prospective study of anal cancer screening in HIV-positive and negative MSM.

OBJECTIVE: The study sought to establish the feasibility and acceptability of anal screening among men MSM. DESIGN: Prospective cohort study. SETTING: Sexual health clinics in tertiary care. PATIENTS: Known HIV-positive and negative MSM who have anoreceptive intercourse. INTERVENTION: Anal screening with human papilloma virus (HPV) testing, liquid-based cytology and high-resolution anoscopy with biopsy of anoscopic abnormalities. Participants completed questionnaires at baseline and at 6 months. RESULTS: Anal HPV was highly prevalent in MSM (HIV-positive, 88% and HIV-negative, 78%). Despite the high prevalence of cytological abnormality in both HIV-positive (46.2%) and negative (35.0%) MSM, almost half of anal intraepithelial neoplasia (AIN) of all grades were associated with negative cytology. Anoscopically directed biopsies detected AIN3 or worse (AIN3+) in 14 of 203 (6.9%) of HIV-positive MSM and three of 81 (3.7%) HIV-negative MSM. The corresponding prevalence of AIN2+ was 26.6 and 20.9%, respectively. One case of AIN3 was detected at the second visit. Screening was considered to be highly acceptable by participants. CONCLUSION: The high prevalence of high-risk-HPV and frequency of false negative cytology in this study suggest that high-resolution anoscopy would have most clinical utility, as a primary screening tool for anal cancer in a high-risk group. The prevalence of AIN3+ in HIV-positive MSM lends support for a policy of screening this group, but the high prevalence of lower grade lesions which do not warrant immediate treatment and the limitations of treating high-grade lesions requires careful consideration in terms of a screening policy.

Development of Prognosis in Palliative care Study (PiPS) predictor models to improve prognostication in advanced cancer: prospective cohort study.

OBJECTIVE: To develop a novel prognostic indicator for use in patients with advanced cancer that is significantly better than clinicians' estimates of survival. DESIGN: Prospective multicentre observational cohort study. SETTING: 18 palliative care services in the UK (including hospices, hospital support teams, and community teams). PARTICIPANTS: 1018 patients with locally advanced or metastatic cancer, no longer being treated for cancer, and recently referred to palliative care services. MAIN OUTCOME MEASURES: Performance of a composite model to predict whether patients were likely to survive for "days" (0-13 days), "weeks" (14-55 days), or "months+" (>55 days), compared with actual survival and clinicians' predictions. RESULTS: On multivariate analysis, 11 core variables (pulse rate, general health status, mental test score, performance status, presence of anorexia, presence of any site of metastatic disease, presence of liver metastases, C reactive protein, white blood count, platelet count, and urea) independently predicted both two week and two month survival. Four variables had prognostic significance only for two week survival (dyspnoea, dysphagia, bone metastases, and alanine transaminase), and eight variables had prognostic significance only for two month survival (primary breast cancer, male genital cancer, tiredness, loss of weight, lymphocyte count, neutrophil count, alkaline phosphatase, and albumin). Separate prognostic models were created for patients without (PiPS-A) or with (PiPS-B) blood results. The area under the curve for all models varied between 0.79 and 0.86. Absolute agreement between actual survival and PiPS predictions was 57.3% (after correction for over-optimism). The median survival across the PiPS-A categories was 5, 33, and 92 days and survival across PiPS-B categories was 7, 32, and 100.5 days. All models performed as well as, or better than, clinicians' estimates of survival. CONCLUSIONS: In patients with advanced cancer no longer being treated, a combination of clinical and laboratory variables can reliably predict two week and two month survival.

A study of cellular counting to determine minimum thresholds for adequacy for liquid-based cervical cytology using a survey and counting protocol.

BACKGROUND: Liquid-based cytology (LBC) for cervical screening would benefit from laboratory practice guidelines that define specimen adequacy for reporting of slides. The evidence base required to define cell adequacy should incorporate both ThinPrep™ (TP; Hologic, Inc., Bedford, MA, USA) and SurePath™ (SP; BD Diagnostics, Burlington, NC, USA), the two LBC systems used in the UK cervical screening programmes. OBJECTIVES: The objectives of this study were to determine (1) current practice for reporting LBC in England, Wales and Scotland, (2) a reproducible method for cell counting, (3) the cellularity of slides classified as inadequate, negative or abnormal and (4) the impact of varying cellularity on the likelihood of detecting cytological abnormalities. DESIGN: The study involved four separate arms to pursue each of the four objectives. (1) A questionnaire survey of laboratories was conducted. (2) A standard counting protocol was developed and used by three experienced cytopathologists to determine a reliable and reproducible cell counting method. (3) Slide sets which included a range of cytological abnormalities were each sent to three laboratories for cell counting to study the correlation between cell counts and reported cytological outcomes. (4) Dilution of LBC samples by fluid only (unmixed) or by dilution with a sample containing normal cells (mixed) was performed to study the impact on reporting of reducing either the total cell count or the relative proportion of abnormal to normal cells. SETTING: The study was conducted within the cervical screening programmes in England, Wales and Scotland, using routinely obtained cervical screening samples, and in 56 participating NHS cervical cytology laboratories. PARTICIPANTS: The study involved only routinely obtained cervical screening samples. INTERVENTIONS: There was no clinical intervention. MAIN OUTCOME MEASURES: The main outcome measures were (1) reliability of counting method, (2) correlation of reported cytology grades with cellularity and (3) levels of detection of abnormal cells in progressively diluted cervical samples. RESULTS: Laboratory practice varied in terms of threshold of cellular adequacy and of morphological markers of adequacy. While SP laboratories generally used a minimum acceptable cell count (MACC) of 15,000, the MACC employed by TP laboratories varied between 5000 and 15,000. The cell counting study showed that a standard protocol achieved moderate to strong inter-rater reproducibility. Analysis of slide reporting from laboratories revealed that a large proportion of the samples reported as inadequate had cell counts above a threshold of 15,000 for SP, and 5000 and 10,000 for TP. Inter-rater unanimity was greater among more cellular preparations. Dilution studies demonstrated greater detection of abnormalities in slides with counts above the MACC and among slides with more than 25 dyskaryotic cells. CONCLUSIONS: Variation in laboratory practice demonstrates a requirement for evidence-based standards for designating a MACC. This study has indicated that a MACC of 15,000 and 5000 for SP and TP, respectively, achieves a balance in terms of maintaining sensitivity and low inadequacy rates. FUTURE WORK: The findings of this study should inform the development of laboratory practice guidelines. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Development of Prognosis in Palliative care Study (PiPS) predictor models to improve prognostication in advanced cancer: prospective cohort study.

OBJECTIVE: To develop a novel prognostic indicator for use in patients with advanced cancer that is significantly better than clinicians' estimates of survival. DESIGN: Prospective multicentre observational cohort study. SETTING: 18 palliative care services in the UK (including hospices, hospital support teams, and community teams). PARTICIPANTS: 1018 patients with locally advanced or metastatic cancer, no longer being treated for cancer, and recently referred to palliative care services. MAIN OUTCOME MEASURES: Performance of a composite model to predict whether patients were likely to survive for "days" (0-13 days), "weeks" (14-55 days), or "months+" (>55 days), compared with actual survival and clinicians' predictions. RESULTS: On multivariate analysis, 11 core variables (pulse rate, general health status, mental test score, performance status, presence of anorexia, presence of any site of metastatic disease, presence of liver metastases, C reactive protein, white blood count, platelet count, and urea) independently predicted both two week and two month survival. Four variables had prognostic significance only for two week survival (dyspnoea, dysphagia, bone metastases, and alanine transaminase), and eight variables had prognostic significance only for two month survival (primary breast cancer, male genital cancer, tiredness, loss of weight, lymphocyte count, neutrophil count, alkaline phosphatase, and albumin). Separate prognostic models were created for patients without (PiPS-A) or with (PiPS-B) blood results. The area under the curve for all models varied between 0.79 and 0.86. Absolute agreement between actual survival and PiPS predictions was 57.3% (after correction for over-optimism). The median survival across the PiPS-A categories was 5, 33, and 92 days and survival across PiPS-B categories was 7, 32, and 100.5 days. All models performed as well as, or better than, clinicians' estimates of survival. CONCLUSIONS: In patients with advanced cancer no longer being treated, a combination of clinical and laboratory variables can reliably predict two week and two month survival.

Patients' reports or clinicians' assessments: which are better for prognosticating?

BACKGROUND: The Prognosis in Palliative care Scale (PiPS) predicts survival in advanced cancer patients more accurately than a doctor's or a nurse's estimate. PiPS scores are derived using observer ratings of symptom severity and performance status. The purpose of this study was to determine whether patient-rated data would provide better prognostic estimates than clinician observer ratings. PATIENTS AND METHODS: 1018 subjects with advanced cancer no longer undergoing tumour-directed therapy were recruited to a multi-centre study. Prognostic models were developed using observer ratings, patient ratings or a composite method that used patient ratings when available or else used observer ratings. The performance of the prognostic models was compared by determining the agreement between the models' predictions and the survival of study participants. RESULTS: All three approaches to model development resulted in prognostic scores that were able to differentiate between patients with a survival of 'days', 'weeks' or 'months+'. However, the observer-rated models were significantly (p<0.05) more accurate than the patient-rated models. CONCLUSIONS: A prognostic model derived using observer-rated data was more accurate at predicting survival than a similar model derived using patient self-report measures. This is clinically important because patient-rated data can be burdensome and difficult to obtain in patients with terminal illnesses.

Development of prognosis in palliative care study (PiPS) predictor models to improve prognostication in advanced cancer: prospective cohort study.

OBJECTIVE: To develop a novel prognostic indicator for use in patients with advanced cancer that is significantly better than clinicians' estimates of survival. DESIGN: Prospective multicentre observational cohort study. SETTING: 18 palliative care services in the UK (including hospices, hospital support teams, and community teams). PARTICIPANTS: 1018 patients with locally advanced or metastatic cancer, no longer being treated for cancer, and recently referred to palliative care services. MAIN OUTCOME MEASURES: Performance of a composite model to predict whether patients were likely to survive for "days" (0-13 days), "weeks" (14-55 days), or "months+" (>55 days), compared with actual survival and clinicians' predictions. RESULTS: On multivariate analysis, 11 core variables (pulse rate, general health status, mental test score, performance status, presence of anorexia, presence of any site of metastatic disease, presence of liver metastases, C reactive protein, white blood count, platelet count, and urea) independently predicted both two week and two month survival. Four variables had prognostic significance only for two week survival (dyspnoea, dysphagia, bone metastases, and alanine transaminase), and eight variables had prognostic significance only for two month survival (primary breast cancer, male genital cancer, tiredness, loss of weight, lymphocyte count, neutrophil count, alkaline phosphatase, and albumin). Separate prognostic models were created for patients without (PiPS-A) or with (PiPS-B) blood results. The area under the curve for all models varied between 0.79 and 0.86. Absolute agreement between actual survival and PiPS predictions was 57.3% (after correction for over-optimism). The median survival across the PiPS-A categories was 5, 33, and 92 days and survival across PiPS-B categories was 7, 32, and 100.5 days. All models performed as well as, or better than, clinicians' estimates of survival. CONCLUSIONS: In patients with advanced cancer no longer being treated, a combination of clinical and laboratory variables can reliably predict two week and two month survival.