Anti-Vascular Endothelial Growth Factor Drugs Compared With Panretinal Photocoagulation for the Treatment of Proliferative Diabetic Retinopathy: A Cost-Effectiveness Analysis.

OBJECTIVES: This study aimed to evaluate the cost-effectiveness of anti-vascular endothelial growth factor drugs (anti-VEGFs) compared with panretinal photocoagulation (PRP) for treating proliferative diabetic retinopathy (PDR) in the United Kingdom. METHODS: A discrete event simulation model was developed, informed by individual participant data meta-analysis. The model captures treatment effects on best corrected visual acuity in both eyes, and the occurrence of diabetic macular edema and vitreous hemorrhage. The model also estimates the value of undertaking further research to resolve decision uncertainty. RESULTS: Anti-VEGFs are unlikely to generate clinically meaningful benefits over PRP. The model predicted anti-VEGFs be more costly and similarly effective as PRP, generating 0.029 fewer quality-adjusted life-years at an additional cost of £3688, with a net health benefit of -0.214 at a £20 000 willingness-to-pay threshold. Scenario analysis results suggest that only under very select conditions may anti-VEGFs offer potential for cost-effective treatment of PDR. The consequences of loss to follow-up were an important driver of model outcomes. CONCLUSIONS: Anti-VEGFs are unlikely to be a cost-effective treatment for early PDR compared with PRP. Anti-VEGFs are generally associated with higher costs and similar health outcomes across various scenarios. Although anti-VEGFs were associated with lower diabetic macular edema rates, the number of cases avoided is insufficient to offset the additional treatment costs. Key uncertainties relate to the long-term comparative effectiveness of anti-VEGFs, particularly considering the real-world rates and consequences of treatment nonadherence. Further research on long-term visual acuity and rates of vision-threatening complications may be beneficial in resolving uncertainties.

Ablative and non-surgical therapies for early and very early hepatocellular carcinoma: a systematic review and network meta-analysis.

Background: A wide range of ablative and non-surgical therapies are available for treating small hepatocellular carcinoma in patients with very early or early-stage disease and preserved liver function. Objective: To review and compare the effectiveness of all current ablative and non-surgical therapies for patients with small hepatocellular carcinoma (≤ 3 cm). Design: Systematic review and network meta-analysis. Data sources: Nine databases (March 2021), two trial registries (April 2021) and reference lists of relevant systematic reviews. Review methods: Eligible studies were randomised controlled trials of ablative and non-surgical therapies, versus any comparator, for small hepatocellular carcinoma. Randomised controlled trials were quality assessed using the Cochrane Risk of Bias 2 tool and mapped. The comparative effectiveness of therapies was assessed using network meta-analysis. A threshold analysis was used to identify which comparisons were sensitive to potential changes in the evidence. Where comparisons based on randomised controlled trial evidence were not robust or no randomised controlled trials were identified, a targeted systematic review of non-randomised, prospective comparative studies provided additional data for repeat network meta-analysis and threshold analysis. The feasibility of undertaking economic modelling was explored. A workshop with patients and clinicians was held to discuss the findings and identify key priorities for future research. Results: Thirty-seven randomised controlled trials (with over 3700 relevant patients) were included in the review. The majority were conducted in China or Japan and most had a high risk of bias or some risk of bias concerns. The results of the network meta-analysis were uncertain for most comparisons. There was evidence that percutaneous ethanol injection is inferior to radiofrequency ablation for overall survival (hazard ratio 1.45, 95% credible interval 1.16 to 1.82), progression-free survival (hazard ratio 1.36, 95% credible interval 1.11 to 1.67), overall recurrence (relative risk 1.19, 95% credible interval 1.02 to 1.39) and local recurrence (relative risk 1.80, 95% credible interval 1.19 to 2.71). Percutaneous acid injection was also inferior to radiofrequency ablation for progression-free survival (hazard ratio 1.63, 95% credible interval 1.05 to 2.51). Threshold analysis showed that further evidence could plausibly change the result for some comparisons. Fourteen eligible non-randomised studies were identified (n ≥ 2316); twelve had a high risk of bias so were not included in updated network meta-analyses. Additional non-randomised data, made available by a clinical advisor, were also included (n = 303). There remained a high level of uncertainty in treatment rankings after the network meta-analyses were updated. However, the updated analyses suggested that microwave ablation and resection are superior to percutaneous ethanol injection and percutaneous acid injection for some outcomes. Further research on stereotactic ablative radiotherapy was recommended at the workshop, although it is only appropriate for certain patient subgroups, limiting opportunities for adequately powered trials. Limitations: Many studies were small and of poor quality. No comparative studies were found for some therapies. Conclusions: The existing evidence base has limitations; the uptake of specific ablative therapies in the United Kingdom appears to be based more on technological advancements and ease of use than strong evidence of clinical effectiveness. However, there is evidence that percutaneous ethanol injection and percutaneous acid injection are inferior to radiofrequency ablation, microwave ablation and resection. Study registration: PROSPERO CRD42020221357. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment (HTA) programme (NIHR award ref: NIHR131224) and is published in full in Health Technology Assessment; Vol. 27, No. 29. See the NIHR Funding and Awards website for further award information.

Hepatocellular carcinoma is the most common type of primary liver cancer. There are a range of different treatments available for patients with early hepatocellular carcinoma. We looked for clinical trials in patients with small tumours (up to 3 cm) that compared different treatments. We brought together and analysed the results of these trials to see which treatments were most effective in terms of survival, progression, side effects and quality of life. Overall, the evidence has limitations; many trials had few patients and were of poor quality. Most were from China or Japan, where the common causes of liver disease and treatments available differ from those in the United Kingdom. The results of our analyses were very uncertain so we cannot be sure which treatment is the best overall. We did find that three treatments ­ radiofrequency ablation, microwave ablation and surgery ­ were generally more effective than percutaneous ethanol injection and percutaneous acid injection. There was not enough evidence to be certain which treatment was better when radiofrequency ablation was compared with laser ablation, microwave ablation, proton beam therapy or surgery. We found only poor-quality, non-randomised trials on high-intensity focused ultrasound, cryoablation and irreversible electroporation. There was very little evidence on treatments that combined radiofrequency ablation with other therapies. We found no studies that compared electrochemotherapy, histotripsy, stereotactic ablative radiotherapy or wider radiotherapy techniques with other treatments. Only two studies reported data on quality of life or patient satisfaction. We discussed the findings with patients and clinical experts. Stereotactic ablative radiotherapy was highlighted as a treatment that requires further research; however, it is only appropriate for certain subgroups of patients. Feasibility studies could inform future clinical trials by exploring issues such as whether patients are willing to take part in a trial or find the treatments acceptable.

The effectiveness of ablative and non-surgical therapies for early hepatocellular carcinoma: Systematic review and network meta-analysis of randomised controlled trials.

BACKGROUND & AIMS: Non-surgical therapies are frequently used for patients with early or very early hepatocellular carcinoma (HCC). The aim of this systematic review and network meta-analysis (NMA) was to evaluate and compare the effectiveness of ablative and non-surgical therapies for patients with small HCC. METHODS: Nine databases were searched (March 2021) along with clinical trial registries. Randomised controlled trials (RCTs) of any ablative or non-surgical therapy versus any comparator in patients with HCC ≤3 cm were eligible. Risk of bias (RoB) was assessed using the Cochrane RoB 2 tool. The effectiveness of therapies was compared using NMA. Threshold analysis was undertaken to identify which NMA results had less robust evidence. RESULTS: Thirty-seven eligible RCTs were included (including over 3700 patients). Most were from China (n = 17) or Japan (n = 7). Sample sizes ranged from 30 to 308 patients. The majority had a high RoB or some RoB concerns. No RCTs were identified for some therapies and no RCTs reported quality of life outcomes. The results of the NMA and treatment effectiveness rankings were very uncertain. However, the evidence demonstrated that percutaneous ethanol injection was worse than radiofrequency ablation for overall survival (hazard ratio [HR]: 1.45, 95% credible interval [CrI]: 1.16-1.82), progression-free survival (HR: 1.36, 95% CrI: 1.11-1.67), overall recurrence (relative risk [RR]: 1.19, 95% CrI: 1.02-1.39) and local recurrence (RR: 1.80, 95% CrI: 1.19-2.71). The threshold analysis suggested that robust evidence was lacking for some comparisons. CONCLUSIONS: It is unclear which treatment is most effective for patients with small HCC because of limitations in the evidence base. It is also not known how these treatments would impact on quality of life. Further high quality RCTs are needed to provide robust evidence but may be difficult to undertake.

Respiratory rate responses to both hypercapnia and acidaemia are modified by age in patients with acidosis.

OBJECTIVE: To explore the associations between arterial pO2, pCO2 and pH and how these are modified by age. METHODS: An analysis of 2598 patients admitted with a diagnosis of Covid-19 infection to a large UK teaching hospital. RESULTS: There were inverse associations for arterial pO2, pCO2 and pH with respiratory rate. The effects of pCO2 and pH on respiratory rate were modified by age; older patients had higher respiratory rates at higher pCO2 (p = 0.004) and lower pH (p = 0.007) values. CONCLUSIONS: This suggests that ageing is associated with complex changes in the physiological feedback loops that control respiratory rate. As well as having clinical relevance, this may also impact on the use of respiratory rate in early warning scores across the age range.

Anaemia of acute inflammation: a higher acute systemic inflammatory response is associated with a larger decrease in blood haemoglobin levels in patients with COVID-19 infection.

AIMS: The study tests the hypothesis that a higher acute systemic inflammatory response was associated with a larger decrease in blood hemoglobin levels in patients with Coronavirus 2019 (COVID-19) infection. METHODS: All patients with either suspected or confirmed COVID-19 infection admitted to a busy UK hospital from February 2020 to December 2021 provided data for analysis. The exposure of interest was maximal serum C-reactive protein (CRP) level after COVID-19 during the same admission. RESULTS: A maximal serum CRP >175mg/L was associated with a decrease in blood haemoglobin (-5.0 g/L, 95% confidence interval: -5.9 to -4.2) after adjustment for covariates, including the number of times blood was drawn for analysis.Clinically, for a 55-year-old male patient with a maximum haemoglobin of 150 g/L who was admitted for a 28-day admission, a peak CRP >175 mg/L would be associated with an 11 g/L decrease in blood haemoglobin, compared with only 6 g/L if the maximal CRP was <4 mg/L. CONCLUSIONS: A higher acute systemic inflammatory response is associated with larger decreases in blood haemoglobin levels in patients with COVID-19. This represents an example of anaemia of acute inflammation, and a potential mechanism by which severe disease can increase morbidity and mortality.

An investigation into the effects of climate change on baleen whale distribution in the British Isles.

Climate change is predicted to impact the distribution of many marine species. In the North-East Atlantic and elsewhere in the world, studies indicate that climate change is leading to poleward shifts in cetacean distribution. Here, strandings data collected in the British Isles from 1990 to 2020 were used to assess whether there is evidence of a shift in baleen whale distribution. Linear regression models were used to compare the number of strandings over time between six regions of the British Isles and, whilst the results indicate no significant change in the number of strandings in the most southerly region of the British Isles, there have been significant increases in more northern regions. Data related to stranded minke whales is the primary driver of these increases, with a number of potential variables affecting this trend, including observer effort. These variables are discussed and further research to explore this potential association is suggested.

Inverse association between blood pressure and pulse oximetry accuracy: an observational study in patients with suspected or confirmed COVID-19 infection.

BACKGROUND: Pulse oximeters are a standard non-invasive tool to measure blood oxygen levels, and are used in multiple healthcare settings. It is important to understand the factors affecting their accuracy to be able to use them optimally and safely. This analysis aimed to explore the association of the measurement error of pulse oximeters with systolic BP, diastolic BP and heart rate (HR) within ranges of values commonly observed in clinical practice. METHODS: The study design was a retrospective observational study of all patients admitted to a large teaching hospital with suspected or confirmed COVID-19 infection from February 2020 to December 2021. Data on systolic and diastolic BPs and HR levels were available from the same time period as the pulse oximetry measurements. RESULTS: Data were available for 3420 patients with 5927 observations of blood oxygen saturations as measured by pulse oximetry and ABG sampling within 30 min. The difference in oxygen saturation using the paired pulse oximetry and arterial oxygen saturation difference measurements was inversely associated with systolic BP, increasing by 0.02% with each mm Hg decrease in systolic BP (95% CI 0.00% to 0.03%) over a range of 80-180 mm Hg. Inverse associations were also observed between the error for oxygen saturation as measured by pulse oximetry and with both diastolic BP (+0.03%; 95% CI 0.00% to 0.05%) and HR (+0.04%; 95% CI 0.02% to 0.06% for each unit decrease in the HR). CONCLUSIONS: Care needs to be taken in interpreting pulse oximetry measurements in patients with lower systolic and diastolic BPs, and HRs, as oxygen saturation is overestimated as BP and HR decrease. Confirmation of the oxygen saturation with an ABG may be appropriate in some clinical scenarios.

Expert assessment of the impact of ship-strikes on cetacean welfare using the Welfare Assessment Tool for Wild Cetaceans.

Human activities are increasingly impacting our oceans and the focus tends to be on their environmental impacts, rather than consequences for animal welfare. Global shipping density has quadrupled since 1992. Unsurprisingly, increased levels of vessel collisions with cetaceans have followed this global expansion of shipping. This paper is the first to attempt to consider the severity of ship-strike on individual whale welfare. The methodology of the 'Welfare Assessment Tool for Wild Cetaceans' (WATWC) was used, which is itself based upon the Five Domains model. Expert opinion was sought on six hypothetical but realistic case studies involving humpback whales (Megaptera novaeangliae) struck by ships. Twenty-nine experts in the cetacean and welfare sector took part. They were split into two groups; Group 1 first assessed a case we judged to be the least severe and Group 2 first assessed the most severe. Both groups then additionally assessed the same four further cases. This was to investigate whether the severity of the first case influenced judgements regarding subsequent cases (i.e. expert judgements were relative) or not (i.e. judgements were absolute). No significant difference between the two groups of assessors was found; therefore, the hypothesis of relative scoring was rejected. Experts judged whales may suffer some level (>1) of overall (Domain 5) harm for the rest of their lives following a ship-strike incident. Health, closely followed by Behaviour were found to be the welfare aspects most affected by ship-strikes. Overall, the WATWC shows a robust potential to aid decision-making on wild cetacean welfare.

EarlyCDT Lung blood test for risk classification of solid pulmonary nodules: systematic review and economic evaluation.

BACKGROUND: EarlyCDT Lung (Oncimmune Holdings plc, Nottingham, UK) is a blood test to assess malignancy risk in people with solid pulmonary nodules. It measures the presence of seven lung cancer-associated autoantibodies. Elevated levels of these autoantibodies may indicate malignant disease. The results of the test might be used to modify the risk of malignancy estimated by existing risk calculators, including the Brock and Herder models. OBJECTIVES: The objectives were to determine the diagnostic accuracy, clinical effectiveness and cost-effectiveness of EarlyCDT Lung; and to develop a conceptual model and identify evidence requirements for a robust cost-effectiveness analysis. DATA SOURCES: MEDLINE (including Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE Daily and Ovid MEDLINE), EMBASE, Cochrane Central Register of Controlled Trials, Science Citation Index, EconLit, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Health Technology Assessment database, NHS Economic Evaluation Database ( NHS EED ) and the international Health Technology Assessment database were searched on 8 March 2021. REVIEW METHODS: A systematic review was performed of evidence on EarlyCDT Lung, including diagnostic accuracy, clinical effectiveness and cost-effectiveness. Study quality was assessed with the quality assessment of diagnostic accuracy studies-2 tool. Evidence on other components of the pulmonary nodule diagnostic pathway (computerised tomography surveillance, Brock risk, Herder risk, positron emission tomography-computerised tomography and biopsy) was also reviewed. When feasible, bivariate meta-analyses of diagnostic accuracy were performed. Clinical outcomes were synthesised narratively. A simulation study investigated the clinical impact of using EarlyCDT Lung. Additional reviews of cost-effectiveness studies evaluated (1) other diagnostic strategies for lung cancer and (2) screening approaches for lung cancer. A conceptual model was developed. RESULTS: A total of 47 clinical publications on EarlyCDT Lung were identified, but only five cohorts (695 patients) reported diagnostic accuracy data on patients with pulmonary nodules. All cohorts were small or at high risk of bias. EarlyCDT Lung on its own was found to have poor diagnostic accuracy, with a summary sensitivity of 20.2% (95% confidence interval 10.5% to 35.5%) and specificity of 92.2% (95% confidence interval 86.2% to 95.8%). This sensitivity was substantially lower than that estimated by the manufacturer (41.3%). No evidence on the clinical impact of EarlyCDT Lung was identified. The simulation study suggested that EarlyCDT Lung might potentially have some benefit when considering intermediate risk nodules (10-70% risk) after Herder risk analysis. Two cost-effectiveness studies on EarlyCDT Lung for pulmonary nodules were identified; none was considered suitable to inform the current decision problem. The conceptualisation process identified three core components for a future cost-effectiveness assessment of EarlyCDT Lung: (1) the features of the subpopulations and relevant heterogeneity, (2) the way EarlyCDT Lung test results affect subsequent clinical management decisions and (3) how changes in these decisions can affect outcomes. All reviewed studies linked earlier diagnosis to stage progression and stage shift to final outcomes, but evidence on these components was sparse. LIMITATIONS: The evidence on EarlyCDT Lung among patients with pulmonary nodules was very limited, preventing meta-analyses and economic analyses. CONCLUSIONS: The evidence on EarlyCDT Lung among patients with pulmonary nodules is insufficient to draw any firm conclusions as to its diagnostic accuracy or clinical or economic value. FUTURE WORK: Prospective cohort studies, in which EarlyCDT Lung is used among patients with identified pulmonary nodules, are required to support a future assessment of the clinical and economic value of this test. Studies should investigate the diagnostic accuracy and clinical impact of EarlyCDT Lung in combination with Brock and Herder risk assessments. A well-designed cost-effectiveness study is also required, integrating emerging relevant evidence with the recommendations in this report. STUDY REGISTRATION: This study is registered as PROSPERO CRD42021242248. FUNDING: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 49. See the NIHR Journals Library website for further project information.

People at risk of lung cancer sometimes undergo computerised tomography ( CT ) scans of their lungs. These scans may identify lung nodules that could be cancerous. Currently, CT scans of the lung nodules, or sometimes further positron emission tomography­computerised tomography ( PET-CT ) scans, are used to predict the risk that a nodule is cancerous. EarlyCDT Lung is a blood test that detects substances, called autoantibodies, associated with having cancer. If the autoantibodies are detected, the chance of a lung nodule being cancerous may be substantially increased. This test could help doctors make decisions about whether to treat immediately, carry out further tests or monitor the nodule over time to see if it grows or changes shape. This project examined the evidence on the clinical value of the EarlyCDT Lung test. We reviewed all published studies of EarlyCDT Lung and reanalysed the reported data. We found that there has been little research on EarlyCDT Lung among people with lung nodules (only five studies comprising 695 patients). This makes it difficult to draw any firm conclusions. The evidence suggests that EarlyCDT Lung may not be particularly effective at determining which lung nodules are cancerous, and may not improve diagnosis when compared with using CT and PET - CT scans. However, this is uncertain because the evidence is so limited. This project also looked for evidence on the value for money of the EarlyCDT Lung test in detecting lung cancer, and found no relevant evidence. This means that the value for money of EarlyCDT Lung is largely unknown, and there is currently no good evidence to support further analyses on this. We therefore sought to summarise the information and analyses that would be needed to support a future assessment of the value for money of EarlyCDT Lung.

Estimating interactions in individual participant data meta-analysis: a comparison of methods in practice.

Medical interventions may be more effective in some types of individuals than others and identifying characteristics that modify the effectiveness of an intervention is a cornerstone of precision or stratified medicine. The opportunity for detailed examination of treatment-covariate interactions can be an important driver for undertaking an individual participant data (IPD) meta-analysis, rather than a meta-analysis using aggregate data. A number of recent modelling approaches are available. We apply these methods to the Perinatal Antiplatelet Review of International Studies (PARIS) Collaboration IPD dataset and compare estimates between them. We discuss the practical implications of applying these methods, which may be of interest to aid meta-analysists in the use of these, often complex models.Models compared included the two-stage meta-analysis of interaction terms and one-stage models which fit multiple random effects and separate within and between trial information. Models were fitted for nine covariates and five binary outcomes and results compared.Interaction terms produced by the methods were generally consistent. We show that where data are sparse and there is low heterogeneity in the covariate distributions across trials, the meta-analysis of interactions may produce unstable estimates and have issues with convergence. In this IPD dataset, varying assumptions by using multiple random effects in one-stage models or using only within trial information made little difference to the estimates of treatment-covariate interaction. Method choice will depend on datasets characteristics and individual preference.

The Effect of a Brief Physician-Delivered Neurobiologically Oriented, Cognitive Behavioural Therapy (Brief-CBT) Intervention on Chronic Pain Acceptance in Youth with Chronic Pain-A Randomized Controlled Trial.

At the Stollery Children's Chronic Pain Clinic, new referrals are assessed by an interdisciplinary team. The final part of the intake assessment typically involves an explanation and compassionate validation of the etiology of chronic pain and an invitation to the youth to attend the group outpatient Cognitive Behavioural Therapy (CBT) program, called Pain 101, or to individual outpatient CBT. It was hypothesized that a brief physician-delivered CBT (brief-CBT) intervention at first point of contact improves subsequent pain acceptance. Using a randomized double blinded methodology, 26 participants received a standard intake assessment and 26 the standard assessment plus the brief-CBT intervention. Measures were taken at three points: pre and post-intake assessment and after Pain 101 or individual CBT (or day 30 post-assessment for those attending neither). The primary outcome measure was the Chronic Pain Acceptance Questionnaire­Adolescent version (CPAQ-A). Comparing pre and post-intake measures, there was a significant (p = 0.002) increase in the CPAQ-A scores­four-fold more in the brief-CBT intervention group (p = 0.045). Anxiety (RCADS-T Score) was significantly reduced post-intake and significantly more reduced in the intervention group compared to the control group (p = 0.024). CPAQ-A scores were significantly increased (p < 0.001) (N = 28) and anxiety (RCADs-T) was significantly reduced by the end of Pain 101 (p < 0.003) (N = 29) as was fear of pain as measured by the Tampa Scale for Kinesiophobia (p = 0.021). A physician-delivered brief-CBT intervention significantly and meaningfully increased CPAQ-A scores and reduced anxiety in youth with chronic pain. Furthermore, CBT through Pain 101 is effective at increasing acceptance, as well as reducing anxiety and fear of movement.

Intensive behavioural interventions based on applied behaviour analysis (ABA) for young children with autism: A cost-effectiveness analysis.

BACKGROUND: The economic and social costs of autism are significant. This study evaluates the cost-effectiveness of early intensive Applied Behaviour Analysis (ABA)-based interventions for autistic pre-school children in the UK. METHODS: A de novo economic analysis was developed in Microsoft Excel comparing early intensive ABA-based interventions compared with treatment as usual (TAU). The analysis used 15.5-year time horizon, with costs and benefits discounted a 3.5%. The model structure was based on cohort structure to capture changes in adaptive behaviour and cognitive ability over time. The analysis was informed by an individual patient data (IPD) meta-analysis of available evidence. RESULTS: Adopting a public sector perspective, early intensive ABA-based therapies were associated with greater incremental costs and greater benefits. When pessimistic assumptions were made regarding the long-term effects of treatment incremental costs were £46,103 and incremental quality-adjusted life years (QALYs) were 0.24, resulting in an incremental cost-effectiveness ratio (ICER) of £189,122 per quality-adjusted life year (QALY). When optimistic assumptions were made about long-term effects, incremental costs were £39,233 with incremental benefits of 0.84 QALYs. The resulting ICER was £46,768 per QALY. Scenario analyses emphasised the importance of assumptions made regarding adult outcomes and type of school attended, both of which significantly affect the results of the analysis. CONCLUSIONS: The results of this economic analysis suggest that early intensive ABA-based interventions are unlikely to represent value for money, based on a £20,000 to £30,000 per QALY threshold typically adopted to inform UK healthcare funding decisions. However, important gaps in the available evidence, limit the strength of the conclusions that can be drawn from the presented analysis. Further research, focusing on the trajectory of autistic children following intervention is likely to be highly beneficial to resolving some of these uncertainties.

Predicting Need for Escalation of Care or Death From Repeated Daily Clinical Observations and Laboratory Results in Patients With Severe Acute Respiratory Syndrome Coronavirus 2.

We compared the performance of prognostic tools for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using parameters fitted either at the time of hospital admission or across all time points of an admission. This cohort study used clinical data to model the dynamic change in prognosis of SARS-CoV-2 at a single hospital center in the United Kingdom, including all patients admitted from February 1, 2020, to December 31, 2020, and then followed up for 60 days for intensive care unit (ICU) admission, death, or discharge from the hospital. We incorporated clinical observations and blood tests into 2 time-varying Cox proportional hazards models predicting daily 24- to 48-hour risk of admission to the ICU for those eligible for escalation of care or death for those ineligible for escalation. In developing the model, 491 patients were eligible for ICU escalation and 769 were ineligible for escalation. Our model had good discrimination of daily risk of ICU admission in the validation cohort (n = 1,141; C statistic: C = 0.91, 95% confidence interval: 0.89, 0.94) and our score performed better than other scores (National Early Warning Score 2, International Severe Acute Respiratory and Emerging Infection Comprehensive Clinical Characterisation Collaboration score) calculated using only parameters measured on admission, but it overestimated the risk of escalation (calibration slope = 0.7). A bespoke daily SARS-CoV-2 escalation risk prediction score can predict the need for clinical escalation better than a generic early warning score or a single estimation of risk calculated at admission.

Age modifies both the maximal temperature and inflammatory response in patients with SARS-CoV-2 infection.

OBJECTIVE: To determine the maximal response of the temperature and inflammatory response to SARS-CoV-2 infection and how these are modified by age. METHODS: Participants were patients admitted to hospital with SARS-CoV-2 infection. For each participant, the maximal temperature and serum C-reactive protein (CRP) were identified and stratified by age. In a secondary analysis, these were compared in patients treated before and after dexamethasone. RESULTS: Mean maximal temperature varied by age (p<0.001; ANOVA) with the highest mean maximal temperature of 37.3°C observed in patients aged 30-49 years and decreasing maximal mean temperatures in the older age groups, with the lowest measure of 36.8°C observed in individuals aged 90-99 years. The mean maximal serum CRP also varied across age groups (p<0.001; ANOVA) and increased with age across all age categories from 34.5 mg/dL (95% confidence interval (CI) 22.0-47.0) for individuals aged 20-29 years to 77.6 mg/dL (95% CI 72.0-83.2) in those aged 80-89 years. After dexamethasone became standard treatment for COVID-19 pneumonia, mean maximal CRP decreased by 17 mg/dL (95% CI -22 to -11). CONCLUSION: Age modifies both maximal temperature and systemic inflammatory response in patients with SARS-CoV-2 infection.

The impact of marine debris on cetaceans with consideration of plastics generated by the COVID-19 pandemic.

The accumulation of human-derived debris in the oceans is a global concern and a serious threat to marine wildlife. There is a volume of evidence that points to deleterious effects of marine debris (MD) on cetaceans in terms of both entanglement and ingestion. This review suggests that about 68% of cetacean species are affected by interacting with MD with an increase in the number of species reported to have interacted with it over the past decades. Despite the growing body of evidence, there is an ongoing debate on the actual effects of plastics on cetaceans and, in particular, with reference to the ingestion of microplastics and their potential toxicological and pathogenic effects. Current knowledge suggests that the observed differences in the rate and nature of interactions with plastics are the result of substantial differences in species-specific diving and feeding strategies. Existing projections on the production, use and disposal of plastics suggest a further increase of marine plastic pollution. In this context, the contribution of the ongoing COVID-19 pandemic to marine plastic pollution appears to be substantial, with potentially serious consequences for marine life including cetaceans. Additionally, the COVID-19 pandemic offers an opportunity to investigate the direct links between industry, human behaviours and the effects of MD on cetaceans. This could help inform management, prevention efforts, describe knowledge gaps and guide advancements in research efforts. This review highlights the lack of assessments of population-level effects related to MD and suggests that these could be rather immediate for small populations already under pressure from other anthropogenic activities. Finally, we suggest that MD is not only a pollution, economic and social issue, but also a welfare concern for the species and populations involved.