The Barts Health NHS Trust COVID-19 cohort: characteristics, outcomes and risk scoring of patients in East London.

BACKGROUND: Barts Health National Health Service Trust (BHNHST) serves a diverse population of 2.5 million people in London, UK. We undertook a health services assessment of factors used to evaluate the risk of severe acute respiratory coronavirus 2 (SARS-CoV-2) infection.METHODS: Patients with confirmed polymerase chain reaction (PCR) test results admitted between 1 March and 1 August 2020 were included, alongwith clinician-diagnosed suspected cases. Prognostic factors from the 4C Mortality score and 4C Deterioration scores were extracted from electronic health records and logistic regression was used to quantify the strength of association with 28-day mortality and clinical deterioration using national death registry linkage.RESULTS: Of 2783 patients, 1621 had a confirmed diagnosis, of whom 61% were male and 54% were from Black and Minority Ethnic groups; 26% died within 28 days of admission. Mortality was strongly associated with older age. The 4C mortality score had good stratification of risk with a calibration slope of 1.14 (95% CI 1.01-1.27). It may have under-estimated mortality risk in those with a high respiratory rate or requiring oxygen.CONCLUSION: Patients in this diverse patient cohort had similar mortality associated with prognostic factors to the 4C score derivation sample, but survival might be poorer in those with respiratory failure.

Final Results of the Prospective FH02 Mammographic Surveillance Study of Women Aged 35-39 at Increased Familial Risk of Breast Cancer.

BACKGROUND: Many women who are at increased risk of breast cancer due to a mother or sister diagnosed with breast cancer aged under 40 do not currently qualify for surveillance before 40 years of age. There are almost no available data to assess whether mammography screening aged 35-39 years would be effective in this group, in terms of detection of breast cancer at an early stage or cost effective. METHODS: A cohort screening study (FH02) with annual mammography was devised for women aged 35-39 to assess the sensitivity and screening performance and potential survival of women with identified tumours. FINDINGS: 2899 women were recruited from 12/2006-12/2015. These women underwent 12,086 annual screening mammograms and were followed for 13,365.8 years. A total of 55 breast cancers in 54 women occurred during the study period (one bilateral) with 50 cancers (49 women) (15 CIS) adherent to the screening. Eighty percent (28/35) of invasive cancers were ≤ 2 cm and 80% also lymph node negative. Invasive cancers diagnosed in FH02 were significantly smaller than the comparable (POSH-unscreened prospective) study group (45% (131/293) ≤ 2 cm in POSH vs 80% (28/35) in FH02 p < 0.0001), and were less likely to be lymph-node positive (54% (158/290, 3 unknown) in POSH vs 20% (7/35) in FH02: p = 0.0002. Projected and actual survival were also better than POSH. Overall radiation dose was not higher than in an older screened population at mean dose on study per standard sized breast of 1.5 mGy. INTERPRETATION: Mammography screening aged 35-39 years detects breast cancer at an early stage and is likely to be as effective in reducing mortality as in women at increased breast cancer risk aged 40-49 years.

Breast cancer risk assessment in 8,824 women attending a family history evaluation and screening programme.

Accurate individualized breast cancer risk assessment is essential to provide risk-benefit analysis prior to initiating interventions designed to lower breast cancer risk and start surveillance. We have previously shown that a manual adaptation of Claus tables was as accurate as the Tyrer-Cuzick model and more accurate at predicting breast cancer than the Gail, Claus model and Ford models. Here we reassess the manual model with longer follow up and higher numbers of cancers. Calibration of the manual model was assessed using data from 8,824 women attending the family history evaluation and screening programme in Manchester UK, with a mean follow up of 9.71 years. After exclusion of 40 prevalent cancers, 406 incident breast cancers occurred, and 385.1 were predicted (O/E = 1.05, 95 % CI 0.95-1.16) using the manual model. Predictions were close to that of observed cancers in all risk categories and in all age groups, including women in their forties (O/E = 0.99, 95 % CI 0.83-1.16). Manual risk prediction with use of adjusted Claus tables and curves with modest adjustment for hormonal and reproductive factors was a well-calibrated approach to breast cancer risk estimation in a UK family history clinic.

Strategy for power calculation for interactions: application to a trial of interventions to improve uptake of bowel cancer screening.

Poorer postcodes within 5 regions in England have a lower response to bowel-cancer screening invitations than do richer postcodes. An extension of the sample-size formula for two proportions is used to determine that needed to detect an increase in response rate that varies by deprivation quintile. The proportions plugged into the formula are weighted averages based on the relationship between response and deprivation; the response rate is adjusted to be constant across deprivation quintiles. From a baseline period between October 2006 and January 2009, detection of an absolute or relative increase of at least 1,2,3,4 and 5% in response rate is required for the richest to poorest quintiles respectively because the interventions were chosen as those most likely to have an effect in the lower socioeconomic groups. A computer simulation experiment shows that the approach is more conservative than a likelihood-ratio calculation, and it appears sensible when compared with repeated application of a two-sample calculation at each quintile.