Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

The IDENTIFY study: the investigation and detection of urological neoplasia in patients referred with suspected urinary tract cancer - a multicentre observational study

Objective To evaluate the contemporary prevalence of urinary tract cancer (bladder cancer, upper tract urothelial cancer [UTUC] and renal cancer) in patients referred to secondary care with haematuria, adjusted for established patient risk markers and geographical variation. Patients and Methods This was an international multicentre prospective observational study. We included patients aged ≥16 years, referred to secondary care with suspected urinary tract cancer. Patients with a known or previous urological malignancy were excluded. We estimated the prevalence of bladder cancer, UTUC, renal cancer and prostate cancer; stratified by age, type of haematuria, sex, and smoking. We used a multivariable mixed-effects logistic regression to adjust cancer prevalence for age, type of haematuria, sex, smoking, hospitals, and countries. Results Of the 11 059 patients assessed for eligibility, 10 896 were included from 110 hospitals across 26 countries. The overall adjusted cancer prevalence (n = 2257) was 28.2% (95% confidence interval [CI] 22.3–34.1), bladder cancer (n = 1951) 24.7% (95% CI 19.1–30.2), UTUC (n = 128) 1.14% (95% CI 0.77–1.52), renal cancer (n = 107) 1.05% (95% CI 0.80–1.29), and prostate cancer (n = 124) 1.75% (95% CI 1.32–2.18). The odds ratios for patient risk markers in the model for all cancers were: age 1.04 (95% CI 1.03–1.05; P < 0.001), visible haematuria 3.47 (95% CI 2.90–4.15; P < 0.001), male sex 1.30 (95% CI 1.14–1.50; P < 0.001), and smoking 2.70 (95% CI 2.30–3.18; P < 0.001). Conclusions A better understanding of cancer prevalence across an international population is required to inform clinical guidelines. We are the first to report urinary tract cancer prevalence across an international population in patients referred to secondary care, adjusted for patient risk markers and geographical variation. Bladder cancer was the most prevalent disease. Visible haematuria was the strongest predictor for urinary tract cancer

e-Government Integration with Web Services and Alerts: A Case Study on an Emergency Route Advisory System in Hong Kong

Quick and efficient response to emergency is important for every city. This depends on the quality of the dispatch of emergency service to the scene and back to hospital or other governmental offices. To provide the path of the shortest traveling time is a difficult task, especially if there is traffic jam near the scene. In this paper, we formulate a conceptual model for the transport network and Emergency Route Advisory System (ERAS) implementation architecture handle the emergency response. The ERAS requires information integration from various governmental departments and public services through Web services, such as maintaining the databases of transportation information and traffic condition. Making use of such information, a challenge is to find a time-efficient or costeffective path intelligently. Our ERAS interacts with the call centers of emergency service departments (such as the police, fire services, and ambulances) through alert mechanisms to integrate emergency processes. Through this complex case study, we demonstrate the effectiveness of the use of Web services and alerts in e-Government information and process integration

Case Report: Exome sequencing reveals recurrent RETSAT mutations and a loss-of-function POLDIP2 mutation in a rare undifferentiated tongue sarcoma [version 1; referees: 2 approved]

Soft tissue sarcoma of the tongue represents a very rare head and neck cancer with connective tissue features, and the genetics underlying this rare cancer are largely unknown. There are less than 20 cases reported in the literature thus far. Here, we reported the first whole-exome characterization (>×200 depth) of an undifferentiated sarcoma of the tongue in a 31-year-old male. Even with a very good sequencing depth, only 19 nonsynonymous mutations were found, indicating a relatively low mutation rate of this rare cancer (lower than that of human papillomavirus (HPV)-positive head and neck cancer). Yet, among the few genes that are somatically mutated in this HPV-negative undifferentiated tongue sarcoma, a noticeable deleterious frameshift mutation (with a very high allele frequency of >93%) of a gene for DNA replication and repair, namely POLDIP2 (DNA polymerase delta interacting protein 2), and two recurrent mutations of the adipogenesis and adipocyte differentiation gene RETSAT (retinol saturase), were identified. Thus, somatic events likely affecting adipogenesis and differentiation, as well as potential stem mutations to POLDIP2, may be implicated in the formation of this rare cancer. This identified somatic whole-exome sequencing profile appears to be distinct from that of other reported adult sarcomas from The Cancer Genome Atlas, suggesting a potential unique genetic profile for this rare sarcoma of the tongue. Interestingly, this low somatic mutation rate is unexpectedly found to be accompanied by multiple tumor protein p53 and NOTCH1 germline mutations of the patient’s blood DNA. This may explain the very early age of onset of head and neck cancer, with likely hereditary predisposition. Our findings are, to our knowledge, the first to reveal a unique genetic profile of this very rare undifferentiated sarcoma of the tongue

Estimation of Dermal Exposure to Oil Spill Response and Clean-up Workers after the Deepwater Horizon Disaster

The GuLF STUDY is investigating health outcomes associated with oil spill-related chemical exposures among workers involved in the spill response and clean-up following the Deepwater Horizon disaster. Due to the lack of dermal exposure measurements, we estimated dermal exposures using a deterministic model, which we customized from a previously published model. Workers provided information on the frequency of contact with oil, tar, chemical dispersants applied to the oil spill and sea water, as well as the use of protective equipment, by job/activity/task. Professional judgment by industrial hygienists served as a source of information for other model variables. The model estimated dermal exposures to total hydrocarbons (THC), benzene, ethylbenzene, toluene, xylene, n-hexane (BTEX-H), polycyclic aromatic hydrocarbons (PAHs), and dispersants in GuLF DREAM units (GDUs). Arithmetic means (AMs) of THC exposure estimates across study participants ranged from 0.9) for most of the substances in oil but were lower for some of the substances in tar. These data were linked to the study participants to allow investigation of adverse health effects that may be related to dermal exposures

GuLF DREAM:A Model to Estimate Dermal Exposure Among Oil Spill Response and Clean-up Workers

Tens of thousands of individuals performed oil spill response and clean-up (OSRC) activities following the 'Deepwater Horizon' oil drilling rig explosion in 2010. Many were exposed to oil residues and dispersants. The US National Institute of Environmental Health Sciences assembled a cohort of nearly 33 000 workers to investigate potential adverse health effects of oil spill exposures. Estimates of dermal and inhalation exposure are required for those individuals. Ambient breathing-zone measurements taken at the time of the spill were used to estimate inhalation exposures for participants in the GuLF STUDY (Gulf Long-term Follow-up Study), but no dermal measurements were collected. Consequently, a modelling approach was used to estimate dermal exposures. We sought to modify DREAM (DeRmal Exposure Assessment Method) to optimize the model for assessing exposure to various oil spill-related substances and to incorporate advances in dermal exposure research. Each DREAM parameter was reviewed in the context of literature published since 2000 and modified where appropriate. To reflect the environment in which the OSRC work took place, the model treatment of evaporation was expanded to include vapour pressure and wind speed, and the effect of seawater on exposure was added. The modified model is called GuLF DREAM and exposure is estimated in GuLF DREAM units (GDU). An external validation to assess the performance of the model for oils, tars, and fuels was conducted using available published dermal wipe measurements of heavy fuel oil (HFO) and dermal hand wash measurements of asphalt. Overall, measured exposures had moderate correlations with GDU estimates (r = 0.59) with specific correlations of -0.48 for HFO and 0.68 for asphalt. The GuLF DREAM model described in this article has been used to generate dermal exposure estimates for the GuLF STUDY. Many of the updates made were generic, so the updated model may be useful for other dermal exposure scenarios