Background A possible association between COVID-19 infection and thrombosis, either as a direct consequence of the virus or as a complication of inflammation, is emerging in the literature. Data on the incidence of venous thromboembolism (VTE) are extremely limited. Methods We describe three cases of thromboembolism refractory to heparin treatment, the incidence of VTE in an inpatient cohort, and a case-control study to identify risk factors associated with VTE. Results We identified 274 confirmed (208) or probable (66) COVID-19 patients. 21 (7.7%) were diagnosed with VTE. D-dimer was elevated in both cases (confirmed VTE) and controls (no confirmed VTE) but higher levels were seen in confirmed VTE cases (4.1 vs 1.2 µg/mL, p<0.001). Conclusion Incidence of VTE is high in patients hospitalised with COVID-19. Urgent clinical trials are needed to evaluate the

Background Ibrutinib is a Bruton’s tyrosine-kinase (BTK) inhibitor that is approved as a second-line treatment in chronic lymphocytic leukemia (CLL). While recent trials have demonstrated impressive results for ibrutinib, there remains a paucity of real-world data on its use in the clinical setting. Methods In this single-center study carried out at Brighton and Sussex University Hospitals, we retrospectively compared outcomes in 38 patients with relapsed CLL who received ibrutinib versus those who received conventional first- and second-line therapies. Results Our results demonstrate improved progression-free survival (PFS, p =0.022) with ibrutinib versus conventional second-line therapies and survival comparable to conventional first-line therapies. However, there was a high frequency (81.6%) of adverse events associated with ibrutinib therapy, including 2 cases of death secondary to sepsis and a further 7 cases of discontinuation of treatment due to adverse events. We also identify del13q14.3 as an adverse predictor of response to ibrutinib with respect to both overall survival ( p =0.014) and PFS ( p =0.008), suggesting that these patients may be better suited to receiving the BCL2 inhibitor venetoclax. Conclusion Whilst there is robust evidence for improved outcomes with ibrutinib, we find that survival in patients with del13q14.3 is reduced and that the rate of adverse events and discontinuation in clinical practice is higher than anticipated from clinical trials.

IntroductionClinical trials of pirfenidone and nintedanib have shown similar reduced rates of lung function decline in patients with idiopathic pulmonary fibrosis (IPF). In 2013 NICE approved pirfenidone for use in IPF patients with forced vital capacity (FVC) between 50% and 80% predicted. More recently, nintedanib has been available on an individual patient supply program (IPSP).AimsReporting early experience of nintedanib in two tertiary referral centres, focussing on characterising the treated population, assessing the indications for use, and evaluating adverse effects.MethodAll IPF patients attending two tertiary referral centre ILD clinics who were commenced on nintedanib as part of the IPSP were included. Data were collected retrospectively from clinical records and local clinical databases. Data are presented as mean (range).Results75 patients (mean age 70.8 years (50–85), 76% male). The FVC was 79.2% predicted (35% - 123%) and transfer factor (DLCO) 45.8% predicted (13% - 74%) prior to commencing treatment. 54% of patients were prescribed nintedanib because they did not meet FVC criteria for pirfenidone (FVC >80% in 41% of patients and FVC <50% in 13%). Other indications included refusal of pirfenidone due to the side effect profile (15%) or adverse effects requiring pirfenidone discontinuation (13%). 39 patients (52%) experienced adverse effects on nintedanib, the most common being diarrhoea (25%), nausea (13%), abnormal liver function tests (8%) and lethargy (11%). Adverse effects required nintedanib to be discontinued in 7 (9%) patients (diarrhoea (n = 3), abnormal LFTs (n = 2) and patient choice (n = 2)), dose reduction in 13 (17%) patients, and temporarily stopped and restarted in 9 (12%) patients.ConclusionNintedanib is a relatively new medication and although there are modest numbers in this review only 9% had to discontinue treatment. Diarrhoea is the most quoted side effect from trial data (63% of patients in INPULSIS-2), but in our observational data only one quarter suffered diarrhoea and only 3 patients stopping due to this. Although the data is from early experience the discontinuation rate is favourable compared with published and local data on pirfenidone (drop out rate 15%). This needs continued review to further evaluate drug tolerability and real world efficacy.

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