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The impact of unhelpful pain beliefs on patient outcomes after surgically managed ankle fractures: An embedded observational study
No full textResolution of tuberculosis blood RNA signatures fails to discriminate persistent sputum culture positivity after eight weeks of anti-tuberculous treatment.
Full text linkBACKGROUND: Concerted efforts aim to reduce the burden of 6 months anti-tuberculous treatment for tuberculosis (TB). Treatment cessation at 8 weeks is effective for most but incurs increased risk of disease relapse. We tested the hypothesis that blood RNA signatures or C-reactive protein (CRP) measurements discriminate 8-week sputum culture status, as a prerequisite for a biomarker to stratify risk of relapse following treatment cessation at this time point. METHODS: We identified blood RNA signatures of TB disease or cure by systematic review. We evaluated these signatures and CRP measurements in a pulmonary TB cohort, pre-treatment, at 2 and 8 weeks of treatment, and sustained cure after treatment completion. We tested biomarker discrimination of 8-week sputum culture status using area under the receiver operating characteristic curve (AUROC) analysis and, secondarily, assessed correlation of biomarker scores with time-to-culture positivity at 8 weeks of treatment. RESULTS: 12 blood RNA signatures were reproduced in the dataset from 44 individuals with sputum culture positive pulmonary TB. These normalised over time from TB treatment initiation. 11/44 cases with blood RNA, CRP and sputum culture results were sputum culture positive at 8 weeks of treatment. None of the contemporary blood RNA signatures discriminated sputum culture status at this time point or correlated with bacterial load. CRP achieved modest discrimination with AUROC of 0.69 (95% confidence interval 0.52-0.87). CONCLUSIONS: Selected TB blood RNA signatures and CRP do not provide biomarkers of microbiological clearance to support TB treatment cessation at 8 weeks. Resolution of blood transcriptional host-responses in sputum culture-positive individuals suggests Mycobacterium tuberculosis may colonise the respiratory tract without triggering a detectable immune response
Oral nitrate supplementation improves cardiovascular risk markers in COPD: ON-BC a randomised controlled trial
Full text linkBACKGROUND: Short term studies suggest that dietary nitrate supplementation may improve cardiovascular risk profile, lowering blood pressure (BP) and enhancing endothelial function. It is not clear if these beneficial effects are sustained and whether they apply in people with COPD, who have a worse cardiovascular profile than those without COPD. Nitrate-rich beetroot juice BRJ (NR-BRJ) is a convenient dietary source of nitrate. METHODS: The ON-BC trial was a randomized, double-blind, placebo-controlled parallel group study in stable COPD patients with home systolic BP (SBP) measurement ≥130 mmHg. Participants were randomly allocated (1:1) using computer-generated, block randomization to either 70 mL of NR-BRJ (400 mg NO3 -) (n=40) or an otherwise identical nitrate-depleted placebo juice Pl-BRJ (0 mg NO3 -) (n=41), once daily for 12 weeks. The primary endpoint was between group change in home SBP measurement. Secondary outcomes included change in 6-minute walking distance (6MWD) and measures of endothelial function (reactive hyperaemia index (RHI) and augmentation index (AIx75)) using an EndoPAT device. Plasma nitrate and platelet function were also measured. RESULTS: Compared to placebo, active treatment lowered SBP (Hodges-Lemman treatment effect MD[95% CI]; -4.5[-3.0 to -5.9] improved 6MWD (+30.0 m [15.7 to 44.2], p<0.001), RHI +0.34 (0.03 to 0.63) p=0.03, and AIx75 -7.61% [-14.3 to -0.95], p=0.026. CONCLUSIONS: In people with COPD, prolonged dietary nitrate supplementation in the form of beetroot juice produces a sustained reduction in BP, associated with an improvement in endothelial function and exercise capacity
Exploring the organisation and delivery of falls management in care homes for older people in England
Full text linkBackground
To explore the organisational context of English care homes in delivering falls management and identify barriers and facilitators to help design future service delivery.
Methods
Non-participant observations and semi-structured interviews in one region of England with care home staff, commissioners and individuals involved in the organisation of falls management, care home managers, care home owners and residents. Barriers and facilitators were identified by thematic analysis and mapped against the Consolidated Framework for Implementation Research (CFIR).
Results
17 interviews were undertaken including staff and a resident from three care homes. Delivering falls management in care homes was complex and challenged by difficulties in integration across a disjointed system, workforce challenges and managing complexity of resident needs with multiple competing priorities. Facilitators included consistent and regular multi-disciplinary support, valuing team working within the care home, and between the care home and external agencies, and the ability to retain care home staff who developed and honed skills over time and who valued their advocacy role for residents. Variation in care home environments, and access to healthcare support were highlighted.
Conclusions
The delivery of falls management in care homes is complex and involves a number of interacting systems. Implementation strategies to support future delivery need to consider the pressure on care homes and wider systems, workforce challenges and variation between settings
CORRECTION OF TRAUMA-INDUCED COAGULOPATHY BY GOAL DIRECTED THERAPY: A SECONDARY ANALYSIS OF THE ITACTIC TRIAL.
Full text linkBACKGROUND: Trauma hemorrhage induces a coagulopathy with a high associated mortality rate. The Implementing Treatment Algorithms for the Correction of Trauma Induced Coagulopathy (ITACTIC) randomized trial tested two goal-directed treatment algorithms for coagulation management, one guided by conventional coagulation tests and one by viscoelastic hemostatic assays (viscoelastic). The lack of a difference in 28-day mortality led us to hypothesize that coagulopathic patients received insufficient treatment to correct coagulopathy. METHODS: During ITACTIC, two sites were co-enrolling patients into an ongoing prospective observational study, which included serial blood sampling at the same intervals as in ITACTIC. The subgroup in both studies had conventional and viscoelastic test results for each patient available for analysis. A goal-directed treatment was defined as one triggered by an ITACTIC algorithm. Coagulopathy was defined as ROTEM EXTEM A5 <40mm. The primary outcome was correction of coagulopathy by the 12th unit of red blood cell transfusion during resuscitation. RESULTS: Full viscoelastic and conventional coagulation test results were available for 133 patients. 71% were coagulopathic on admission, and 16% developed a coagulopathy during resuscitation. ITACTIC VHA group patients were more likely to receive goal-directed treatment than the standard group (76% vs 47%, OR 3.73, 95%CI:1.64-8.49, p=0.002). However, only 54% of patients received goal-directed treatment, and only 20% corrected their coagulopathy (vs 0% with empiric treatment alone, not significant). Median time to first goal-directed treatment was 68(53-88) minutes for viscoelastic and 110(77-123) minutes for standard, p=0.005. CONCLUSION: In ITACTIC, many bleeding trauma patients did not receive an indicated goal-direct treatment. Interventions arrived late during resuscitation and were only partially effective at correcting coagulopathy