Patient characteristics and predictors of mortality in 470 adults admitted to a district general hospital in England with Covid-19.

Understanding risk factors for death from Covid-19 is key to providing good quality clinical care. We assessed the presenting characteristics of the 'first wave' of patients with Covid-19 at Royal Oldham Hospital, UK and undertook logistic regression modelling to investigate factors associated with death. Of 470 patients admitted, 169 (36%) died. The median age was 71 years (interquartile range 57-82), and 255 (54.3%) were men. The most common comorbidities were hypertension (n = 218, 46.4%), diabetes (n = 143, 30.4%) and chronic neurological disease (n = 123, 26.1%). The most frequent complications were acute kidney injury (AKI) (n = 157, 33.4%) and myocardial injury (n = 21, 4.5%). Forty-three (9.1%) patients required intubation and ventilation, and 39 (8.3%) received non-invasive ventilation. Independent risk factors for death were increasing age (odds ratio (OR) per 10 year increase above 40 years 1.87, 95% confidence interval (CI) 1.57-2.27), hypertension (OR 1.72, 95% CI 1.10-2.70), cancer (OR 2.20, 95% CI 1.27-3.81), platelets <150 × 103/µl (OR 1.93, 95% CI 1.13-3.30), C-reactive protein ≥100 µg/ml (OR 1.68, 95% CI 1.05-2.68), >50% chest radiograph infiltrates (OR 2.09, 95% CI 1.16-3.77) and AKI (OR 2.60, 95% CI 1.64-4.13). There was no independent association between death and gender, ethnicity, deprivation level, fever, SpO2/FiO2, lymphopoenia or other comorbidities. These findings will inform clinical and shared decision making, including use of respiratory support and therapeutic agents.

Factors associated with participation of Alberta dairy farmers in a voluntary, management-based Johne's disease control program.

The Alberta Johne's Disease Initiative (AJDI) is a voluntary, management-based prevention and control program for Johne's disease (JD), a wasting disease in ruminants that causes substantial economic losses to the cattle industry. Despite extensive communication about the program's benefits and low cost to participating producers, approximately 35% of Alberta dairy farmers have not enrolled in the AJDI. Therefore, the objective was to identify differences between AJDI nonparticipants and participants that may influence enrollment. Standardized questionnaires were conducted in person on 163 farms not participating and 61 farms participating in the AJDI. Data collected included demographic characteristics, internal factors (e.g., attitudes and beliefs of the farmer toward JD and the AJDI), external factors (e.g., farmers' JD knowledge and on-farm goals and constraints), as well as farmers' use and influence of various information sources. Nonparticipants and participants differed in at least some aspects of all studied categories. Based on logistic regression, participating farms had larger herds, higher self-assessed knowledge of JD, better understanding of AJDI details before participation, and used their veterinarian more often to get information about new management practices and technologies when compared with nonparticipants. In contrast, nonparticipants indicated that time was a major on-farm constraint and that participation in the AJDI would take too much time. They also indicated that they preferred to wait and see how the program worked on other farms before they participated.

External validation of the Oldham composite Covid-19 associated mortality model (OCCAM), a prognostic model for death in patients hospitalised with Covid-19.

OBJECTIVE: External validation of the Oldham Composite Covid-19 associated Mortality Model (OCCAM), a prognostic model for Covid-19 mortality in hospitalised patients comprised of age, history of hypertension, current or previous malignancy, admission platelet count < 150 × 103/µL, admission CRP ≥ 100 µg/mL, acute kidney injury (AKI), and radiographic evidence of > 50% total lung field infiltrates. PATIENTS AND METHODS: Retrospective study assessing discrimination (c-statistic) and calibration of OCCAM for death in hospital or within 30 days of discharge. 300 adults admitted to six district general and teaching hospitals in North West England for treatment of Covid-19 between September 2020 and February 2021 were included. RESULTS: Two hundred and ninety-seven patients were included in the validation cohort analysis, with a mortality rate of 32.8%. The c-statistic was 0.794 (95% confidence interval 0.742-0.847) vs. 0.805 (95% confidence interval 0.766 - 0.844) in the development cohort. Visual inspection of calibration plots demonstrate excellent calibration across risk groups, with a calibration slope for the external validation cohort of 0.963. CONCLUSION: The OCCAM model is an effective prognostic tool that can be utilised at the time of initial patient assessment to aid decisions around admission and discharge, use of therapeutics, and shared decision-making with patients. Clinicians should remain aware of the need for ongoing validation of all Covid-19 prognostic models in light of changes in host immunity and emerging variants.

Harnessing lipid signaling pathways to target specialized pro-angiogenic neutrophil subsets for regenerative immunotherapy.

To gain insights into neutrophil heterogeneity dynamics in the context of sterile inflammation and wound healing, we performed a pseudotime analysis of single-cell flow cytometry data using the spanning-tree progression analysis of density-normalized events algorithm. This enables us to view neutrophil transitional subsets along a pseudotime trajectory and identify distinct VEGFR1, VEGFR2, and CXCR4 high-expressing pro-angiogenic neutrophils. While the proresolving lipid mediator aspirin-triggered resolvin D1 (AT-RvD1) has a known ability to limit neutrophil infiltration, our analysis uncovers a mode of action in which AT-RvD1 leads to inflammation resolution through the selective reprogramming toward a therapeutic neutrophil subset. This accumulation leads to enhanced vascular remodeling in the skinfold window chamber and a proregenerative shift in macrophage and dendritic cell phenotype, resulting in improved wound closure after skin transplantation. As the targeting of functional immune subsets becomes the key to regenerative immunotherapies, single-cell pseudotime analysis tools will be vital in this field.

Response rates to combination therapy for chronic HCV infection in a clinical setting and derivation of probability tables for individual patient management.

Evidence for efficacy of established treatment guidelines for chronic hepatitis C virus (HCV) disease is based on multinational randomized controlled trials (RCTs). Strategies for managing HCV, however, require an assessment of the effectiveness of intervention in routine clinical practice. We report the outcomes of combination therapy in a large cohort of HCV-infected individuals in the UK. A total of 347 (113 genotype 1, 234 genotype non-1) patients were treated with pegylated interferon and ribavirin according to current guidelines. Forty-two (37.2%) of those with genotype 1 infection and 164 (70.1%) with genotype non-1 infection achieved sustained viral response (SVR). Thirty-nine (11%) patients withdrew from treatment. In addition to viral genotype, factors predictive of a response to therapy were age at start of treatment and disease stage on pretreatment liver biopsy. Multivariate regression analysis demonstrated that the effects of age [odds ratio 0.5; 95% confidence interval (0.31-0.82) per 10-year increment (P = 0.006)] were confined to genotype 1 disease. In order to further inform the management of the individual patient, a multivariate logistic model was used to predict the probability of SVR for subgroups defined by disease stage, genotype and age at commencement of therapy. This model revealed striking differences in predicted response rates between subgroups and provided a strong rationale for early treatment, particularly for those with genotype 1 disease. Our study demonstrates that results comparable with those of RCTs can be achieved in clinical practice, and suggests that prediction of response rates based on probability modelling will provide a valuable adjunct to individual patient management.

Prognostic Value and Development of a Scoring System in Horses With Systemic Inflammatory Response Syndrome.

BACKGROUND: Despite its widespread use in equine medicine, the clinical value of the systemic inflammatory response syndrome (SIRS) concept in horses remains unknown. OBJECTIVES: To study the prognostic value of measures of SIRS in horses and identify the best model of severe SIRS to predict outcome. ANIMALS: A total of 479 consecutive adult horse emergency admissions to a private primary referral practice. METHODS: Prospective observational study. All adult horses admitted for emergency treatment over the study period were included. Multivariate logistic regression and stepwise model selection were used. RESULTS: Each of the 4 SIRS criteria was associated with outcome in this population. Thirty-one percent of emergency cases had 2 or more abnormal SIRS criteria on admission and were defined as SIRS cases. SIRS was associated with increased odds of death (odds ratio [OR] = 8.22; 95% CI, 4.61-15.18; P < .001), an effect mainly found for acute gastrointestinal cases. SIRS cases were assigned a SIRS score of 2, 3, or 4, according to the number of abnormal SIRS criteria fulfilled on admission, and SIRS3 and SIRS4 cases had increased odds of death compared to SIRS2 cases (OR = 4.45; 95% CI, 1.78-11.15; P = .002). A model of severe SIRS including the SIRS score, blood lactate concentration, and color of the mucous membranes best predicted outcome in this population of horses. CONCLUSIONS AND CLINICAL IMPORTANCE: Systemic inflammatory response syndrome is associated with an increased risk of death in adult horses presenting with acute gastrointestinal illnesses. The model of severe SIRS proposed in this study could be used to assess the status and prognosis of adult equine emergency admissions.

A clinical audit cycle of post-operative hypothermia in dogs.

OBJECTIVES: Use of clinical audits to assess and improve perioperative hypothermia management in client-owned dogs. METHODS: Two clinical audits were performed. In Audit 1 data were collected to determine the incidence and duration of perioperative hypothermia (defined as rectal temperatures <37·0°C). The results from Audit 1 were used to reach consensus on changes to be implemented to improve temperature management, including re-defining hypothermia as rectal temperature <37·5°C. Audit 2 was performed after 1 month with changes in place. RESULTS: Audit 1 revealed a high incidence of post-operative hypothermia (88·0%) and prolonged time periods (7·5 hours) to reach normothermia. Consensus changes were to use a forced air warmer on all dogs and measure rectal temperatures hourly post-operatively until temperature ≥37·5°C. After 1 month with the implemented changes, Audit 2 identified a significant reduction in the time to achieve a rectal temperature of ≥37·5°C, with 75% of dogs achieving this goal by 3·5 hours. The incidence of hypothermia at tracheal extubation remained high in Audit 2 (97·3% with a rectal temperature <37·5°C). CLINICAL SIGNIFICANCE: Post-operative hypothermia was improved through simple changes in practice, showing that clinical audit is a useful tool for monitoring post-operative hypothermia and improving patient care. Overall management of perioperative hypothermia could be further improved with earlier intervention.

Comparison of endovascular aneurysm repair with open repair in patients with abdominal aortic aneurysm (EVAR trial 1), 30-day operative mortality results: randomised controlled trial.

BACKGROUND: Endovascular aneurysm repair (EVAR) is a new technology to treat patients with abdominal aortic aneurysm (AAA) when the anatomy is suitable. Uncertainty exists about how endovascular repair compares with conventional open surgery. EVAR trial 1 was instigated to compare these treatments in patients judged fit for open AAA repair. METHODS: Between 1999 and 2003, 1082 elective (non-emergency) patients were randomised to receive either EVAR (n=543) or open AAA repair (n=539). Patients aged at least 60 years with aneurysms of diameter 5.5 cm or more, who were fit enough for open surgical repair (anaesthetically and medically well enough for the procedure), were recruited for the study at 41 British hospitals proficient in the EVAR technique. The primary outcome measure is all-cause mortality and these results will be released in 2005. The primary analysis presented here is operative mortality by intention to treat and a secondary analysis was done in per-protocol patients. FINDINGS: Patients (983 men, 99 women) had a mean age of 74 years (SD 6) and mean AAA diameter of 6.5 cm (SD 1). 1047 (97%) patients underwent AAA repair and 1008 (93%) received their allocated treatment. 30-day mortality in the EVAR group was 1.7% (9/531) versus 4.7% (24/516) in the open repair group (odds ratio 0.35 [95% CI 0.16-0.77], p=0.009). By per-protocol analysis, 30-day mortality for EVAR was 1.6% (8/512) versus 4.6% (23/496) for open repair (0.33 [0.15-0.74], p=0.007). Secondary interventions were more common in patients allocated EVAR (9.8% vs 5.8%, p=0.02). INTERPRETATION: In patients with large AAAs, treatment by EVAR reduced the 30-day operative mortality by two-thirds compared with open repair. Any change in clinical practice should await durability and longer term results.

Cross-Atlantic modification and validation of the A Tool to Assess Quality of Life in Idiopathic Pulmonary Fibrosis (ATAQ-IPF-cA).

RATIONALE: The A Tool to Assess Quality of Life in Idiopathic Pulmonary Fibrosis (ATAQ-IPF) was developed in the USA to assess health-related quality of life in patients with IPF. It is likely that some of the original ATAQ-IPF items perform differently when applied in different countries. This paper reports results of a study conducted to identify the need to refine the content of the ATAQ-IPF to minimise cross-country bias between the USA and the UK. METHODS: The ATAQ-IPF and other study measures were completed by patients attending specialist IPF clinics in the USA and UK. Rasch analysis was used to determine which items performed differently across countries (USA vs UK) and refine the original ATAQ-IPF to an instrument without cross-country bias (ATAQ-IPF-cA). Preliminary validation of the modified instrument was examined by assessing correlations between ATAQ-IPF-cA scores and scores from dyspnoea-specific patient-reported outcome (PRO) measures. RESULTS: 139 patients with IPF (USA=74; UK=65) participated in the study. A total of 41 items and 4 domains were removed from the original, 86-item instrument to yield the 43 items and 10 domains of the ATAQ-IPF-cA. Each domain had good fit to the Rasch model, internal consistency was comparable to the corresponding domains for the original ATAQ-IPF, and validity was supported by significant correlations between its scores and scores from dyspnoea-specific PROs. CONCLUSIONS: The reliability and validity of the substantially shortened ATAQ-IPF-cA are acceptable and comparable to the original instrument. We recommend use of the ATAQ-IPF-cA in IPF studies in which participants are enrolled from the USA and UK.

Secondary interventions and mortality following endovascular aortic aneurysm repair: device-specific results from the UK EVAR trials.

OBJECTIVES: To compare secondary intervention rate, aneurysm-related mortality and all-cause mortality for patients receiving elective endovascular aneurysm repair (EVAR) for large abdominal aortic aneurysms with different commercially available endografts. DESIGN, MATERIALS & METHODS: In the EVAR 1 and 2 multi-centre trials, the principal endografts used were Zenith and Talent and these are compared in 505 patients from EVAR 1 and 143 patients from EVAR 2 followed-up for an average of 3.8 years until 31st December 2005. Outcomes were analysed by Cox proportional hazards regression, with adjustments for potential confounding risk factors and centre. Gore/Excluder graft outcomes also are reported. RESULTS: Across the two trials the secondary intervention rates were 7.0 and 9.4 per 100 patient years for Zenith and Talent grafts respectively, adjusted hazard ratio 0.77 [95%CI 0.52-1.12]. Aneurysm-related mortality was 1.2 and 1.4 per 100 patient years for Zenith and Talent grafts respectively, adjusted hazard ratio 0.90 [95%CI 0.37-2.19]. All-cause mortality was 8.5 and 10.3 per 100 patient years for Zenith and Talent grafts respectively, adjusted hazard ratio 0.81 [95%CI 0.58-1.14]. The direction of all results was similar when the two trials were analysed separately. CONCLUSION: There was no significant difference in the performance of the two endografts but the direction of results was slightly in favour of patients with Zenith (versus Talent) endografts.

Gender difference in HIV-1 RNA viral loads.

OBJECTIVES: To test and characterize the dependence of viral load on gender in different countries and racial groups as a function of CD4 T-cell count. METHODS: Plasma viral load data were analysed for > 30,000 HIV-infected patients attending clinics in the USA [HIV Insight (Cerner Corporation, Vienna, VA, USA) and Plum Data Mining LLC (East Meadow, NY, USA) databases] and the Netherlands (Athena database; HIV Monitoring Foundation, Amsterdam, Netherlands). Log-normal regression models were used to test for an effect of gender on viral load while adjusting for covariates and allowing the effect to depend on CD4 T-cell count. Sensitivity analyses were performed to test the robustness of conclusions to assumptions regarding viral loads below the lower limit of quantification (LLOQ). RESULTS: After adjusting for covariates, women had (nonsignificantly) lower viral loads than men (HIV Insight: -0.053 log(10) HIV-1 RNA copies/mL, P = 0.202; Athena: -0.005 log(10) copies/mL, P = 0.667; Plum: -0.072 log(10) copies/mL, P = 0.273). However, further investigation revealed that the gender effect depended on CD4 T-cell count. Women had consistently higher viral loads than men when CD4 T-cell counts were at most 50 cells/microL, and consistently lower viral loads than men when CD4 T-cell counts were greater than 350 cells/microL. These effects were remarkably consistent when estimated independently for the racial groups with sufficient data available in the HIV Insight and Plum databases. CONCLUSIONS: The consistent relationship between gender-related differences in viral load and CD4 T-cell count demonstrated here explains the diverse findings previously published.

Diagnostic and treatment behaviour in children with chronic respiratory symptoms: relationship with socioeconomic factors.

BACKGROUND: The prevalence and severity of asthma is believed to increase with increasing socioeconomic deprivation. The relationship between asthma diagnosis, symptoms, diagnostic accuracy, and socioeconomic deprivation as determined by Townsend scores was determined in Sheffield schoolchildren. METHODS: All 6021 schoolchildren aged 8-9 years in one school year in Sheffield were given a parent respondent survey based on International Survey of Asthma and Allergies in Childhood (ISAAC) questions. RESULTS: 5011/6021 (83.2%) questionnaires were returned. Postcode data were available in 4131 replies (82.4%) and were used to assign a composite deprivation score (Townsend score). Scores were divided into five quintiles, with group 1 being least and group 5 being most deprived. A positive trend was observed from group 1 to group 5 for the prevalence of wheeze in the previous 12 months, wheeze attacks >or=4/year, nocturnal wheeze and cough (all p<0.001), cough and/or wheeze "most times" with exertion (p<0.03), current asthma (p<0.001), and significant asthma symptoms (p<0.001). No significant trend was observed for lifetime wheeze or attacks of speech limiting wheeze. There were no significant trends in the prevalence of current asthmatic children without significant symptoms (overdiagnosis) or children with significant asthma symptoms but no current asthma diagnosis (underdiagnosis) across the social groups. There was a significant negative trend in the ratio of asthma medication to asthma diagnosis from least to most deprived groups (p<0.001). CONCLUSIONS: Asthma morbidity and severity increase according to the level of socioeconomic deprivation. This may be due to differences in environment, asthma management, and/or symptom reporting. Diagnostic accuracy does not vary significantly across deprivation groups but children living in areas of least deprivation and taking asthma medication are less likely to be labelled as having asthma, suggesting diagnostic labelling bias.

Increasing prevalence of asthma diagnosis and symptoms in children is confined to mild symptoms.

BACKGROUND: The prevalence of childhood asthma is increasing but few studies have investigated trends in asthma severity. We investigated trends in asthma diagnosis and symptom morbidity between an eight year time period in a paired prevalence study. METHODS: All children in one single school year aged 8-9 years in the city of Sheffield were given a parent respondent questionnaire in 1991 and 1999 based on questions from the International Survey of Asthma and Allergy in Children (ISAAC). Data were obtained regarding the prevalence of asthma and wheeze and current (12 month) prevalences of wheeze attacks, speech limiting wheeze, nocturnal cough and wheeze, and exertional symptoms. RESULTS: The response rates in 1991 and 1999 were 4580/5321 (85.3%) and 5011/6021 (83.2%), respectively. There were significant increases between the two surveys in the prevalence of asthma ever (19.9% v 29.7%, mean difference 11.9%, 95% confidence interval (CI) 10.16 to 13.57, p<0.001), current asthma (10.3% v 13.0%, mean difference 2.7%, 95% CI 1.44 to 4.03, p<0.001), wheeze ever (30.3% v 35.8%, mean difference 5.7%, 95% CI 3.76 to 7.56, p<0.001), wheeze in the previous 12 months (17.0% v 19.4%, mean difference 2.5, 95% CI 0.95 to 4.07, p<0.01), and reporting of medication use (16.9% v 20%, mean difference 3.0%, 95% CI 1.46 to 4.62, p<0.001). There were also significant increases in reported hayfever and eczema diagnoses. CONCLUSIONS: Diagnostic labelling of asthma and lifetime prevalence of wheeze has increased. The current 12 month point prevalence of wheeze has increased but this is confined to occasional symptoms. The increased medication rate may be responsible for the static prevalence of severe asthma symptoms. The significant proportion of children receiving medication but reporting no asthma symptoms identified from our 1999 survey suggests that some children are being inappropriately treated or overtreated.