Prevention and early treatment of the long-term physical effects of COVID-19 in adults: design of a randomised controlled trial of resistance exercise-CISCO-21.

BACKGROUND: Coronavirus disease-19 (COVID-19) infection causes persistent health problems such as breathlessness, chest pain and fatigue, and therapies for the prevention and early treatment of post-COVID-19 syndromes are needed. Accordingly, we are investigating the effect of a resistance exercise intervention on exercise capacity and health status following COVID-19 infection. METHODS: A two-arm randomised, controlled clinical trial including 220 adults with a diagnosis of COVID-19 in the preceding 6 months. Participants will be classified according to clinical presentation: Group A, not hospitalised due to COVID but persisting symptoms for at least 4 weeks leading to medical review; Group B, discharged after an admission for COVID and with persistent symptoms for at least 4 weeks; or Group C, convalescing in hospital after an admission for COVID. Participants will be randomised to usual care or usual care plus a personalised and pragmatic resistance exercise intervention for 12 weeks. The primary outcome is the incremental shuttle walks test (ISWT) 3 months after randomisation with secondary outcomes including spirometry, grip strength, short performance physical battery (SPPB), frailty status, contacts with healthcare professionals, hospitalisation and questionnaires assessing health-related quality of life, physical activity, fatigue and dyspnoea. DISCUSSION: Ethical approval has been granted by the National Health Service (NHS) West of Scotland Research Ethics Committee (REC) (reference: GN20CA537) and recruitment is ongoing. Trial findings will be disseminated through patient and public forums, scientific conferences and journals. TRIAL REGISTRATION: ClinicialTrials.gov NCT04900961 . Prospectively registered on 25 May 2021.

D-dimer assays--a help or hindrance in suspected pulmonary thromboembolism assessment?

BACKGROUND: Suspected pulmonary thromboembolism (PTE) is a common presentation to acute medical units and can cause diagnostic difficulty. National guidelines on PTE management highlight the need for clinical probability assessment and D-dimer assays to ensure appropriate use of diagnostic imaging. D-dimers are used widely in UK hospitals, yet concern exists regarding their misuse. AIMS: In this study we aimed to assess the impact of the introduction of D-dimer assays, combined with clinical probability assessment, for evaluation of suspected PTE in our unit. MATERIALS AND METHODS: This was a prospective audit of all patients presenting with suspected PTE over two 12-week periods, exactly 1 year apart. D-dimers were introduced into our unit between these two periods. We recorded the clinical probability score, potential causes of false-positive D-dimer assay, diagnostic imaging result, patient outcome, admission rates, and length of inpatient stay. STATISTICAL ANALYSIS: Categorical variables were compared using a 2 x 2 chi-square test or Fisher's exact test. Groups were compared utilizing the two-sample t-test or Mann-Whitney U test. RESULTS: A total of 190 patients were included in the study; 65% were female. PTE was confirmed in 8.4%. Patients in both audit periods were comparable with regard to suitability for D-dimer measurement. Following D-dimer introduction, 40 out of 110 patients in period 2 could be discharged directly from the emergency department. Of those admitted to hospital, the median length of stay was significantly reduced in period 2 (3 days in period 1 vs 1 day in period 2; P=0.0007). Use of diagnostic imaging was significantly reduced following the introduction of D-dimers (90% in period 1 vs 40% in period 2; P<0.0001). The positive diagnostic yield for PTE on CT pulmonary angiogram (CTPA) increased significantly from 10% in period 1 to 23% in period 2 (P=0.039). CONCLUSION: D-dimers must be used judiciously in the assessment of suspected PTE. Appropriate use of D-dimers can provide many benefits, including reductions in diagnostic imaging (and thus radiation exposure), admission rates, and length of inpatient stay.

Clinical audit: management of acute severe asthma in west Glasgow.

BACKGROUND: The U.K. has 75,000 hospital admissions and over 1500 deaths from asthma annually. The British Thoracic Society (BTS) guidelines represent the recognised standard for acute asthma management. We assessed the degree of conformity with these guidelines in an acute medical unit. METHODOLOGY: Data from consecutive admissions were collected prospectively. Practice was audited in October December 2005 and October 2006 - January 2007. Between cycles an educational programme was instigated, RESULTS: Fifty-eight patients were included. Clinical parameters were well recorded in both cycles. Peak expiratory flow was consistently under-recorded (72% at admission; 67% in monitoring). in monitoring). Severity assessment was documented at 55% and 66% in cycle one and two respectively. Of these, the assessment was incorrect in 33% in cycle one and 21% in cycle two. All misclassifications of severity were underestimates. All life-threatening attacks were not identified. No improvement occurred between cycles. Overall, 60% of patients were inappropriately treated according to BTS guidelines, 40% due to under-treatment. Under-treatment occurred more frequently in cycle two compared with cycle one (57% vs. 24%, p = 0.007), predominantly due to inadequate treatment of life-threatening asthma. CONCLUSION: Management of acute asthma in a large, urban teaching hospital is suboptimal. Educational intervention failed to improve care; more comprehensive strategies are required.

A murine model of early Pseudomonas aeruginosa lung disease with transition to chronic infection.

Pseudomonas aeruginosa (PA) remains an important pathogen in patients with cystic fibrosis (CF) lung disease as well as non-CF bronchiectasis and chronic obstructive airways disease. Initial infections are cleared but chronic infection with mucoid strains ensues in the majority of CF patients and specific interventions to prevent this critical infection transition are lacking. The PA bead model has been widely used to study pulmonary P.aeruginosa infection but has limitations in animal husbandry and in accurately mimicking human disease. We have developed an adapted agar bead murine model using a clinical mucoid strain that demonstrates the key features of transition from transitory to chronic airways infection. Infected animals show very limited acute morbidity and mortality, but undergo infection-related weight loss and neutrophilic inflammation, development of anti-pseudomonal antibodies, variable bacterial clearance, endobronchial infection and microbial adaptation with PA small colony variants. We anticipate this model will allow research into the host and microbial factors governing this critical period in Pseudomonas aeruginosa pulmonary pathogenesis when transition to chronicity is occurring.

Survival from malignant mesothelioma: where are we now?

BACKGROUND: The prognosis of malignant pleural mesothelioma has traditionally been poor. Whether this remains the case compared to historical data and within a specific geographical location is uncertain. Knowledge of predictive factors for survival with malignant pleural mesothelioma is also inadequate. METHODS: We conducted a retrospective local database analysis to determine overall prognosis of patients with malignant pleural mesothelioma and evaluate the influence of demographic characteristics, histological subtype and laboratory parameters. Patients with histological diagnoses of malignant pleural mesothelioma held on the NHS Grampian pathology database between 2002 and 2012 were analysed. Data on baseline demographics, mode of diagnosis, histological sub-type, and survival and serum laboratory parameters, were analysed; time to death was examined using Cox regression analyses. RESULTS: A total of 114 patients with malignant pleural mesothelioma were included in the analysis. The median survival was 345 days (IQR 99-600). Sarcomatoid malignant pleural mesothelioma carried a significantly worse prognosis with median survival of 125 days (IQR 44-289) vs 334 days (IQR 126-715) for biphasic, 412 days (IQR 201-656) for epithelioid and 345 days (IQR 99-600) for those with no definitive typing. Individuals who did not receive chemotherapy experienced a significantly worse prognosis (hazard ratio 2.7; 95%CI 1.5-4.7; p = 0.001), while a low albumin and raised urea at time of diagnosis were also associated with a significantly poorer prognosis. CONCLUSION: The survival of patients with malignant pleural mesothelioma remains poor and typically around 1 year. The presence of raised urea and low albumin is associated with a poorer prognosis, while patients with a good performance status and few co-morbidities should be encouraged to receive chemotherapy.