The adverse effects and choice of injectable agents in MDR-TB: amikacin or capreomycin

The prolonged use of injectable agents in a regimen for the treatment of multidrug-resistant tuberculosis (MDR-TB) is recommended by the World Health Organization, despite its association with ototoxicity and nephrotoxicity. We undertook this study to look at the relative adverse effects of capreomycin and amikacin. We reviewed the case notes of 100 consecutive patients treated at four MDR-TB treatment centers in the United Kingdom. The median total duration of treatment with an injectable agent was 178 days (interquartile range [IQR], 109 to 192 days; n = 73) for those with MDR-TB, 179 days (IQR, 104 to 192 days; n = 12) for those with MDR-TB plus fluoroquinolone resistance, and 558 days (IQR, 324 to 735 days; n = 8) for those with extensively drug-resistant tuberculosis (XDR-TB). Injectable use was longer for those started with capreomycin (183 days; IQR, 123 to 197 days) than those started with amikacin (119 days; IQR, 83 to 177 days) (P = 0.002). Excluding patients with XDR-TB, 51 of 85 (60%) patients were treated with an injectable for over 6 months and 12 of 85 (14%) were treated with an injectable for over 8 months. Forty percent of all patients discontinued the injectable due to hearing loss. Fifty-five percent of patients experienced ototoxicity, which was 5 times (hazard ratio [HR], 5.2; 95% confidence interval [CI], 1.2 to 22.6; P = 0.03) more likely to occur in those started on amikacin than in those treated with capreomycin only. Amikacin was associated with less hypokalemia than capreomycin (odds ratio, 0.28; 95% CI, 0.11 to 0.72), with 5 of 37 (14%) patients stopping capreomycin due to recurrent electrolyte loss. There was no difference in the number of patients experiencing a rise in the creatinine level of >1.5 times the baseline level. Hearing loss is frequent in this cohort, though its incidence is significantly lower in those starting capreomycin, which should be given greater consideration as a first-line agent

The impact of gastrointestinal symptoms and dermatological injuries on nutritional intake and hydration status during ultramarathon events

BACKGROUND: Debilitating gastrointestinal symptoms (GIS) and dermatological injuries (DI) are common during and after endurance events and have been linked to performance decrements, event withdrawal, and issues requiring medical attention. The study aimed to determine whether GIS and DI affect food and fluid intake, and nutritional and hydration status, of ultramarathon runners during multi-stage (MSUM) and 24-h continuous (24 h) ultramarathons. METHODS: Ad libitum food and fluid intakes of ultramarathon runners (MSUM n = 54; 24 h n = 22) were recorded throughout both events and analysed by dietary analysis software. Body mass and urinary ketones were determined, and blood samples were taken, before and immediately after running. A medical log was used to monitor symptoms and injuries throughout both events. RESULTS: GIS were reported by 85 and 73 % of ultramarathon runners throughout MSUM and 24 h, respectively. GIS during MSUM were associated with reduced total daily, during, and post-stage energy and macronutrient intakes (p < 0.05), whereas GIS during 24 h did not alter nutritional variables. Throughout the MSUM 89 % of ultramarathon runners reported DI. DI during MSUM were associated with reduced carbohydrate (p < 0.05) intake during running and protein intake post-stage (p < 0.05). DI during 24 h were low; thus, comparative analyses were not possible. Daily, during running, and post-stage energy, macronutrient and water intake variables were observed to be lower with severity of GIS and DI (p < 0.05) throughout the MSUM only. CONCLUSIONS: GIS during the MSUM, but not the 24 h, compromised nutritional intake. DI presence and severity also compromised nutrient intake during running and recovery in the MSUM

Development and validation of the ISARIC 4C Deterioration model for adults hospitalised with COVID-19: a prospective cohort study.

BACKGROUND: Prognostic models to predict the risk of clinical deterioration in acute COVID-19 cases are urgently required to inform clinical management decisions. METHODS: We developed and validated a multivariable logistic regression model for in-hospital clinical deterioration (defined as any requirement of ventilatory support or critical care, or death) among consecutively hospitalised adults with highly suspected or confirmed COVID-19 who were prospectively recruited to the International Severe Acute Respiratory and Emerging Infections Consortium Coronavirus Clinical Characterisation Consortium (ISARIC4C) study across 260 hospitals in England, Scotland, and Wales. Candidate predictors that were specified a priori were considered for inclusion in the model on the basis of previous prognostic scores and emerging literature describing routinely measured biomarkers associated with COVID-19 prognosis. We used internal-external cross-validation to evaluate discrimination, calibration, and clinical utility across eight National Health Service (NHS) regions in the development cohort. We further validated the final model in held-out data from an additional NHS region (London). FINDINGS: 74 944 participants (recruited between Feb 6 and Aug 26, 2020) were included, of whom 31 924 (43·2%) of 73 948 with available outcomes met the composite clinical deterioration outcome. In internal-external cross-validation in the development cohort of 66 705 participants, the selected model (comprising 11 predictors routinely measured at the point of hospital admission) showed consistent discrimination, calibration, and clinical utility across all eight NHS regions. In held-out data from London (n=8239), the model showed a similarly consistent performance (C-statistic 0·77 [95% CI 0·76 to 0·78]; calibration-in-the-large 0·00 [-0·05 to 0·05]); calibration slope 0·96 [0·91 to 1·01]), and greater net benefit than any other reproducible prognostic model. INTERPRETATION: The 4C Deterioration model has strong potential for clinical utility and generalisability to predict clinical deterioration and inform decision making among adults hospitalised with COVID-19. FUNDING: National Institute for Health Research (NIHR), UK Medical Research Council, Wellcome Trust, Department for International Development, Bill & Melinda Gates Foundation, EU Platform for European Preparedness Against (Re-)emerging Epidemics, NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool, NIHR HPRU in Respiratory Infections at Imperial College London

Towards coordinated regional multi-satellite InSAR volcano observations:results from the Latin America pilot project

Within Latin America, about 319 volcanoes have been active in the Holocene, but 202 of these volcanoes have no seismic, deformation or gas monitoring. Following the 2012 Santorini Report on satellite Earth Observation and Geohazards, the Committee on Earth Observation Satellites (CEOS) developed a 4-year pilot project (2013-2017) to demonstrate how satellite observations can be used to monitor large numbers of volcanoes cost-effectively, particularly in areas with scarce instrumentation and/or difficult access. The pilot aims to improve disaster risk management (DRM) by working directly with the volcano observatories that are governmentally responsible for volcano monitoring as well as with the international space agencies (ESA, CSA, ASI, DLR, JAXA, NASA, CNES). The goal is to make sure that the most useful data are collected at each volcano following the guidelines of the Santorini report that observation frequency is related to volcano activity, and to communicate the results to the local institutions in a timely fashion. Here we highlight how coordinated multi-satellite observations have been used by volcano observatories to monitor volcanoes and respond to crises. Our primary tool is measurements of ground deformation made by Interferometric Synthetic Aperture Radar (InSAR), which have been used in conjunction with other observations to determine the alert level at these volcanoes, served as an independent check on ground sensors, guided the deployment of ground instruments, and aided situational awareness. During this time period, we find 26 volcanoes deforming, including 18 of the 28 volcanoes that erupted – those eruptions without deformation were less than 2 on the VEI scale. Another 7 volcanoes were restless and the volcano observatories requested satellite observations, but no deformation was detected. We describe the lessons learned about the data products and information that are most needed by the volcano observatories in the different countries using information collected by questionnaires. We propose a practical strategy for regional to global satellite volcano monitoring for use by volcano observatories in Latin America and elsewhere to realize the vision of the Santorini report

Biology Direct:celebrating 7 years of open, published peer review

Approved for review, but I'll leave this to the OAR manager's discretion whether or not this should be uploaded, as it is a journal editorial and not a peer-reviewed piece of literature

A cost comparison of amikacin therapy with bedaquiline, for drug-resistant tuberculosis in the UK.

OBJECTIVES: Prioritisation of oral bedaquiline over the injectable agents in the treatment of multidrug-resistant Tuberculosis (MDR-TB) in the World Health Organisations (WHO) 2019 guidelines prompted this UK analysis of cost implications. The objective was to estimate the costs of amikacin versus bedaquiline in MDR TB treatment regimens using a historical cohort where the injectable agents were the standard of care. METHODS: This was a retrospective study using a known cohort of UK patients treated with an injectable agent, with data available on resource use, costs for the use of amikacin were compared with those for bedaquiline, based on recommended monitoring for bedaquiline. RESULTS: The estimated cost of treatment per patient had mean (sd) of £27236 (4952) for the observed injectable group, £30264 (3392) and 36309 (3901) for the 6 and 8 month amikacin groups, and £31760 (2092) for the bedaquiline group. The cost in the bedaquiline group was £30772 (1855) with a 10 % reduction and £27079 (1234) with a 33% reduction in in-patient stay. CONCLUSIONS: In most scenarios, bedaquiline is close to cost neutral compared with injectable therapy, especially if, as expected, some reduction in duration of admission is possible as a result of bedaquiline's more rapid culture conversion

'Long-COVID': a cross-sectional study of persisting symptoms, biomarker and imaging abnormalities following hospitalisation for COVID-19

Large numbers of people are being discharged from hospital following COVID-19 without assessment of recovery. In 384 patients (mean age 59.9 years; 62% male) followed a median 54 days post discharge, 53% reported persistent breathlessness, 34% cough and 69% fatigue. 14.6% had depression. In those discharged with elevated biomarkers, 30.1% and 9.5% had persistently elevated d-dimer and C reactive protein, respectively. 38% of chest radiographs remained abnormal with 9% deteriorating. Systematic follow-up after hospitalisation with COVID-19 identifies the trajectory of physical and psychological symptom burden, recovery of blood biomarkers and imaging which could be used to inform the need for rehabilitation and/or further investigation