Our aim was to estimate the burden of fatal disease attributable to excess adiposity in England and Wales in 2003 and 2015 and to explore the sensitivity of the estimates to the assumptions and ...methods used.
A spreadsheet implementation of the World Health Organization's (WHO) Comparative Risk Assessment (CRA) methodology for continuously distributed exposures was used. For our base case, adiposity-related risks were assumed to be minimal with a mean (SD) BMI of 21 (1) Kg m-2. All cause mortality risks for 2015 were taken from the Government Actuary and alternative compositions by cause derived. Disease-specific relative risks by BMI were taken from the CRA project and varied in sensitivity analyses.
Under base case methods and assumptions for 2003, approximately 41,000 deaths and a loss of 1.05 years of life expectancy were attributed to excess adiposity. Seventy-seven percent of all diabetic deaths, 23% of all ischaemic heart disease deaths and 14% of all cerebrovascular disease deaths were attributed to excess adiposity. Predictions for 2015 were found to be more sensitive to assumptions about the future course of mortality risks for diabetes than to variation in the assumed trend in BMI. On less favourable assumptions the attributable loss of life expectancy in 2015 would rise modestly to 1.28 years.
Excess adiposity appears to contribute materially but modestly to mortality risks in England and Wales and this contribution is likely to increase in the future. Uncertainty centres on future trends of associated diseases, especially diabetes. The robustness of these estimates is limited by the lack of control for correlated risks by stratification and by the empirical uncertainty surrounding the effects of prolonged excess adiposity beginning in adolescence.
Description A 59-year-old female ex-smoker with morbid obesity and chronic obstructive pulmonary disease presented with persistent breathlessness despite multiple courses of oral antibiotics.
Abstract 4846
Primary mediastinal B cell lymphoma (PMBL) is an aggressive subtype of diffuse large B-cell lymphoma derived from thymic B cells. As data presented by Dunleavy et al has shown ...remarkable overall survival with rituximab and dose-adjusted EPOCH (R DA EPOCH) (1), we adopted this strategy as standard of care for fit patients with PMBL in our centres from 2010. Although interim PET after 2 cycles (PET2) is of demonstrable predictive value in activated and germinal centre B-cell DLBL (ABC/GCB DLBL) and has become routine practice in many centres, its role in monitoring PMBL response to treatment is unclear. We therefore decided to evaluate the utility of PET2 in prognosticating PMBL outcome.
A multicenter retrospective analysis was performed on PMBL patients treated with R DA EPOCH (6 to 8 cycles) and evaluated with PET at baseline (PET0), after two chemotherapy cycles (PET2), and post treatment. Radiotherapy (RT) treatment was decided on a case by case basis. A cohort of ABC/GCB DLBL patients treated with R-CHOP and evaluated with PET2 served as an internal control. Histological diagnosis with reviewed by a haematopathologist and PET scans were assessed by a nuclear medicine physician specialising in lymphoma imaging. Fisher's exact test was used to compare categorical variables, and positive predictive value of PET2 for relapse was calculated.
Ten cases of PMBL were identified. Median age was 35 years (17 – 49) and 62% were female. Three (30%) patients had stage 1 disease, 4 (40%) were stage 2, and 3 (30%) were stage 4. Eight (80%) patients had PET0. Two patients had no PET0 due to clinical urgency of presentation. PET2 was negative in only 1 (10%) patient (Deauville 2) and positive in 9 (90%) patients (Deauville 4). SUVmax reduction PET0 to PET2 for the single PET2 negative case was 24.7 to 2.7. Mean SUVmax reduction for the other 7 paired PET0 to PET2 cases was 17.6 to 6.0. At the time of analysis, all 10 patients are alive. Seven patients have completed treatment with median follow up was 16 months. All 7 patients (100%) achieved an end of treatment PET negative remission (Deauville 1 or 2) with 3 (43%) patients receiving RT. Of the 9 PET2 positive patients, 1 (11%) relapsed at 17 months post PET2 but remains in remission following salvage treatment and autograft.
The ABC/GCB DLBL internal control group consisted of 36 patients treated uniformly with R-CHOP. In contrast to PMBL, PET2 was positive in only 10 (28%) cases and negative in 26 (82%) cases. PET2 positivity was significantly more frequent in the PMBL cohort (p = 0.007). The positive predictive value for future relapse of PET2 in PMBL patients who have completed treatment was 16%.
Excellent results were achieved with R DA EPOCH, in line with previous data(1). Similar to prior studies, a high rate of PET2 negativity was achieved in ABC/GCB DLBL treated with R-CHOP (82%). However, only a minority of PMBL patients treated with R DA EPOCH were PET2 negative (10%), yet all patients who completed therapy were PET negative at the end of treatment. PET2 had a very low positive predictive value in identifying patients at risk of relapse (16%).
No relevant conflicts of interest to declare.
A healthy, asymptomatic man living in London, presented with seeing ‘worms’ in his toilet for two successive summer seasons. Repeated microscopic examination and cultures of both his faeces and urine ...were normal. He was empirically treated with multiple courses of antihelminthics without resolution of this problem. A sample of the worms was obtained, and positively identified as arthropod larvae under microscopic examination. These larvae do not parasitically colonise humans. It was subsequently deduced that a flying arthropod (most likely Culex pipiens mosquito) had laid eggs in standing toilet water, and the hatched larvae had been mistaken for parasitic worms. The patient was declared free of parasites and remains healthy. This case illustrates the dangers of starting empirical treatment without positive confirmation of causative organisms, which can result in unnecessary and potentially harmful treatment.
A healthy, asymptomatic man living in London, presented with seeing ‘worms’ in his toilet for two successive summer seasons. Repeated microscopic examination and cultures of both his faeces and urine ...were normal. He was empirically treated with multiple courses of antihelminthics without resolution of this problem. A sample of the worms was obtained, and positively identified as arthropod larvae under microscopic examination. These larvae do not parasitically colonise humans. It was subsequently deduced that a flying arthropod (most likely Culex pipiens mosquito) had laid eggs in standing toilet water, and the hatched larvae had been mistaken for parasitic worms. The patient was declared free of parasites and remains healthy. This case illustrates the dangers of starting empirical treatment without positive confirmation of causative organisms, which can result in unnecessary and potentially harmful treatment.
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