The PASTIS trial: testing tadalafil for possible use in vascular cognitive impairment

Introduction: There are few randomized clinical trials in vascular cognitive impairment (VCI). This trial tested the hypothesis that the PDE5 inhibitor tadalafil, a widely used vasodilator, increases cerebral blood flow (CBF) in older people with symptomatic small vessel disease, the main cause of VCI. Methods: In a double‐blind, placebo‐controlled, cross‐over trial, participants received tadalafil (20 mg) and placebo on two visits ≥7 days apart (randomized to order of treatment). The primary endpoint, change in subcortical CBF, was measured by arterial spin labelling. Results: Tadalafil increased CBF non‐significantly in all subcortical areas (N = 55, age: 66.8 (8.6) years) with greatest treatment effect within white matter hyperintensities (+9.8%, P = .0960). There were incidental treatment effects on systolic and diastolic blood pressure (–7.8, –4.9 mmHg; P < .001). No serious adverse events were observed. Discussion: This trial did not identify a significant treatment effect of single‐administration tadalafil on subcortical CBF. To detect treatment effects may require different dosing regimens

Testing the cognitive effects of tadalafil. Neuropsychological secondary outcomes from the PASTIS trial

Cerebral small vessel disease (SVD) is a major cause of cognitive impairment in older people. As secondary endpoints in a phase-2 randomised clinical trial, we tested the effects of single administration of a widely-used PDE5 inhibitor, tadalafil, on cognitive performance in older people with SVD. In a double-blinded, placebo-controlled, cross-over trial, participants received tadalafil (20 mg) and placebo on two visits ≥ 7 days apart (randomised to order of treatment). The Montreal Cognitive Assessment (MOCA) was administered at baseline, alongside a measure to estimate optimal intellectual ability (Test of Premorbid Function). Then, before and after treatment, a battery of neuropsychological tests was administered, assessing aspects of attention, information processing speed, working memory and executive function. Sixty-five participants were recruited and 55 completed the protocol (N = 55, age: 66.8 (8.6) years, range 52–87; 15/40 female/male). Median MOCA score was 26 (IQR: 23, 27], range 15–30). No significant treatment effects were seen in any of the neuropsychological tests. There was a trend towards improved performance on Digit Span Forward (treatment effect 0.37, C.I. 0.01, 0.72; P = 0.0521). We did not identify significant treatment effects of single-administration tadalafil on neuropsychological performance in older people with SVD. The trend observed on Digit Span Forward may help to inform future studies

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Symmetrical crypsis and asymmetrical signalling in the cuttlefish Sepia officinalis

The salience of bilateral symmetry to humans has led to the suggestion that camouflage may be enhanced in asymmetrical patterns. However, the importance of bilateral symmetry in visual signals (and overall morphology) may constrain the evolution of asymmetrical camouflage, resulting in the bilaterally symmetrical cryptic patterns that we see throughout the animal kingdom. This study investigates the cuttlefish (Sepia officinalis), which can control the degree of symmetry in its coloration. Ten juvenile S. officinalis were filmed in two behavioural contexts (cryptic and threatened) to test the prediction that cryptic patterns will be expressed more asymmetrically than an anti-predator signal known as the ‘deimatic display’. Cryptic body patterns, particularly those with a disruptive function, were found to exhibit a high degree of bilateral symmetry. By contrast, the components of the deimatic display were often expressed asymmetrically. These results are contrary to the predicted use of symmetry in defensive coloration, indicating that the role of symmetry in both crypsis and visual signalling is not as straightforward as previously suggested

Uncertainty in breast, prostate, and colorectal cancer: implications for supportive care

Purpose: The aim of this paper was to identify and explore the literature for key aspects of uncertainty experienced by patients who have been diagnosed with breast, prostate, or colorectal cancer. Organizing Construct: Throughout the cancer journey important decisions are made about treatments, symptom control, and supportive care and many approaches have been adopted to examine coping and uncertainty associated with a cancer diagnosis. Uncertainty and its associated attributes, such as stress or anxiety, fluctuate across the disease trajectory. To appreciate the changing nature of uncertainty one should consider its effect on specific patient groups by considering the available evidence. Methods: A comprehensive literature search that was focused on reviews and studies about uncertainty in cancer patients was conducted in PubMed and CINAHL. In total, 40 articles were identified that indicated uncertainty in patients with breast, prostate, or colorectal cancer, although the emphasis in each differed according to the nature and treatment of the disease. Findings: Uncertainty was found to comprise three main themes: uncertainty because of limited or lack of information, uncertainty concerning the course and treatment choices related to the disease, and uncertainty related to everyday life and coping with the disease. Conclusions: Uncertainty influences patients' experiences of their cancer and their coping. Whilst it might be impossible to avoid uncertainty entirely, its negative effects might be ameliorated by understanding patients' specific needs along the disease trajectory of breast, prostate, and colorectal cancer

Test–retest reliability of arterial spin labelling for cerebral blood flow in older adults with small vessel disease

Cerebral small vessel disease (SVD) is common in older people and is associated with lacunar stroke, white matter hyperintensities (WMH) and vascular cognitive impairment. Cerebral blood flow (CBF) is reduced in SVD, particularly within white matter. Here we quantified test–retest reliability in CBF measurements using pseudo-continuous arterial spin labelling (pCASL) in older adults with clinical and radiological evidence of SVD (N=54, mean (SD): 66.9 (8.7) years, 15 females/39 males). We generated whole-brain CBF maps on two visits at least 7 days apart (mean (SD): 20 (19), range 7-117 days). Test–retest reliability for CBF was high in all tissue types, with intra-class correlation coefficient [95%CI]: 0.758 [0.616, 0.852] for whole brain, 0.842 [0.743, 0.905] for total grey matter, 0.771 [0.636, 0.861] for deep grey matter (caudate-putamen and thalamus), 0.872 [0.790, 0.923] for normal-appearing white matter (NAWM) and 0.780 [0.650, 0.866] for WMH (all p<0.001). ANCOVA models indicated significant decline in CBF in total grey matter, deep grey matter and NAWM with increasing age and diastolic blood pressure (all p<0.001). CBF was lower in males relative to females (p=0.013 for total grey matter, p=0.004 for NAWM). We conclude that pCASL has high test–retest reliability as a quantitative measure of CBF in older adults with SVD. These findings support the use of pCASL in routine clinical imaging and as a clinical trial endpoint. All data come from the PASTIS trial, prospectively registered at: https://eudract.ema.europa.eu (2015-001235-20, registered 13/05/2015), http://www.clinicaltrials.gov (NCT02450253, registered 21/05/2015). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12975-021-00983-5

The psychological needs of patients receiving chemotherapy: an exploration of nurse perceptions

This study explored the perceptions of a group of registered oncology nurses about the psychological needs of patients with cancer receiving chemotherapy and how the nurses meet these. Eight nurses who provided chemotherapy and were working in a local oncology centre participated. A semi-structured interview was used to explore nurses’ perceptions, and how they meet these patients’ needs. The analysis of interview transcripts revealed that these nurses agreed that patients with cancer receiving chemotherapy had psychological needs. Moreover, they were conscious that some of the physical side-effects could have a psychological impact on the patients. Although nurses did not use any assessment tool for psychological assessment, they identified two main stages during the treatment when patients needed more psychological support: at the beginning and at the end of the chemotherapy. They explained how they tried to meet patients’ psychological needs but they also mentioned several factors that influenced the psychological support that patients received