Multicentre analysis of incidental findings on low-resolution CT attenuation correction images : an extended study

Objective: To review new incidental findings detected on low-resolution CT attenuation correction (CTAC) images acquired during single-photon emission CT-CT myocardial perfusion imaging as an extension to our initial study. Methods: CTAC images acquired as part of myocardial perfusion imaging performed using single-photon emission CT at four UK nuclear medicine centres were evaluated as part of a multicentre study. New incidental findings that were considered to be clinically significant were evaluated further. Positive-predictive value (PPV) was determined at the time of definitive diagnosis. Results: Out of 3485 patients, 962 (28%) patients had a positive finding on the CTAC image, of which 824 (24%) were new findings. 84 (2.4%) patients had findings that were considered clinically significant at the time of the CTAC report and which had not been previously diagnosed. However, only 10 (0.29%) of these had findings that were confirmed as clinically significant, with the potential to be detrimental to patient outcome, after follow-up and definitive diagnosis. Conclusion: The overall PPV from all centres over the 2-year period was 12%. Each centre achieved what we considered to be low PPVs with no significant difference between the present and initial studies. The additional data from the combined studies show that, statistically, there is no significant difference between the PPVs from any of the centres. We conclude that routine reporting of CTAC images is not beneficial. Advances in knowledge: This study combined with the previous study offers a unique evaluation of new clinically significant incidental findings on low-resolution CT images in an attempt to determine the benefit of reporting the CTAC images

Online mindfulness stress intervention for family carers of children and adults with intellectual disabilities : feasibility randomized controlled trial

Objectives: Family carers of people with intellectual disabilities (ID) are twice as likely as other carers to experience stress and mental ill-health, but research exploring interventions is sparse. Online mindfulness may provide an accessible, cost-effective resource. The addition of guided telephone support could help to tailor an existing intervention for this population. A feasibility randomized controlled trial (RCT) was conducted to inform the development of a definitive RCT. Methods: Sixty participants were randomized to complete Be Mindful (a brief online mindfulness intervention) either with or without additional Peer Mentor support. Feasibility of recruitment, retention, intervention adherence, and acceptability of study design were examined. Preliminary analyses were undertaken on participant-reported outcomes pre- and post-intervention. Eighteen semi-structured interviews were conducted as a process evaluation. Results: Feasibility outcomes indicate that it would be possible to recruit and retain (88%) participants to a definitive RCT, and that the study design and intervention are acceptable. The addition of guided telephone support was not burdensome; indeed, it was additionally motivating. Telephone support can be delivered with high fidelity, but this is inconsistent and requires further piloting. Preliminary comparison data indicate small, but non-significant, improvements for participants receiving guided telephone support relative to those who did not over time. Conclusions: It is feasible to deliver online mindfulness with additional telephone guided support to family carers of people with ID, and this may lead to small benefits over receiving online mindfulness alone. A definitive RCT can be planned to examine the effectiveness and cost-effectiveness of this intervention

The acute effects of cannabidiol on the neural correlates of reward anticipation and feedback in healthy volunteers

Background: Cannabidiol has potential therapeutic benefits for people with psychiatric disorders characterised by reward function impairment. There is existing evidence that cannabidiol may influence some aspects of reward processing. However, it is unknown whether cannabidiol acutely affects brain function underpinning reward anticipation and feedback. Hypotheses: We predicted that cannabidiol would augment brain activity associated with reward anticipation and feedback. Methods: We administered a single 600 mg oral dose of cannabidiol and matched placebo to 23 healthy participants in a double-blind, placebo-controlled, repeated-measures design. We employed the monetary incentive delay task during functional magnetic resonance imaging to assay the neural correlates of reward anticipation and feedback. We conducted whole brain analyses and region-of-interest analyses in pre-specified reward-related brain regions. Results: The monetary incentive delay task elicited expected brain activity during reward anticipation and feedback, including in the insula, caudate, nucleus accumbens, anterior cingulate and orbitofrontal cortex. However, across the whole brain, we did not find any evidence that cannabidiol altered reward-related brain activity. Moreover, our Bayesian analyses showed that activity in our regions-of-interest was similar following cannabidiol and placebo. Additionally, our behavioural measures of motivation for reward did not show a significant difference between cannabidiol and placebo. Discussion: Cannabidiol did not acutely affect the neural correlates of reward anticipation and feedback in healthy participants. Future research should explore the effects of cannabidiol on different components of reward processing, employ different doses and administration regimens, and test its reward-related effects in people with psychiatric disorders

The Effects of Acute Δ⁹-Tetrahydrocannabinol on Striatal Glutamatergic Function:A Proton Magnetic Resonance Spectroscopy Study

Background: Cannabis and its main psychoactive component, Δ9-tetrahydrocannabinol (THC), can elicit transient psychotic symptoms. A key candidate biological mechanism of how THC induces psychotic symptoms is the modulation of glutamate in the brain. We sought to investigate the effects of acute THC administration on striatal glutamate levels and its relationship to the induction of psychotic symptoms. Methods: We used proton magnetic resonance spectroscopy to measure glutamate levels in the striatum in 20 healthy participants after THC (15 mg, oral) and matched placebo administration in a randomized, double-blind, placebo-controlled design. Psychotic symptoms were measured using the Psychotomimetic States Inventory. Results: We found that THC administration did not significantly change glutamate (glutamate plus glutamine relative to creatine) concentration in the striatum (p =.58; scaled Jeffreys-Zellner-Siow Bayes factor = 4.29). THC increased psychotic symptoms, but the severity of these symptoms was not correlated with striatal glutamate levels. Conclusions: These findings suggest that oral administration of 15 mg of THC does not result in altered striatal glutamate levels. Further work is needed to clarify the effects of THC on striatal glutamate.</p

The acute effects of cannabidiol on emotional processing and anxiety: a neurocognitive imaging study

Rationale: There is growing interest in the therapeutic potential of cannabidiol (CBD) across a range of psychiatric disorders. CBD has been found to reduce anxiety during experimentally induced stress in anxious individuals and healthy controls. However, the mechanisms underlying the putative anxiolytic effects of CBD are unknown. // Objectives: We sought to investigate the behavioural and neural effects of a single dose of CBD vs. placebo on a range of emotion-related measures to test cognitive-mechanistic models of its effects on anxiety. // Methods: We conducted a randomised, double-blind, placebo-controlled, crossover, acute oral challenge of 600 mg of CBD in 24 healthy participants on emotional processing, with neuroimaging (viewing emotional faces during functional magnetic resonance imaging) and cognitive (emotional appraisal) measures as well as subjective response to experimentally induced anxiety. // Results: CBD did not produce effects on brain responses to emotional faces and cognitive measures of emotional processing, or modulate experimentally induced anxiety, relative to placebo. // Conclusions: Given the rising popularity of CBD for its putative medical benefits, these findings question whether further research is warranted to investigate the clinical potential of CBD for the treatment of anxiety disorders

The effects of Acute Δ9-tetrahydrocannabinol on striatal glutamatergic function: a proton magnetic resonance spectroscopy study

Background: Cannabis and its main psychoactive component, Δ9-tetrahydrocannabinol (THC), can elicit transient psychotic symptoms. A key candidate biological mechanism of how THC induces psychotic symptoms is the modulation of glutamate in the brain. We sought to investigate the effects of acute THC administration on striatal glutamate levels and its relationship to the induction of psychotic symptoms. Methods: We used proton magnetic resonance spectroscopy to measure glutamate levels in the striatum in 20 healthy participants after THC (15 mg, oral) and matched placebo administration in a randomized, double-blind, placebo-controlled design. Psychotic symptoms were measured using the Psychotomimetic States Inventory. Results: We found that THC administration did not significantly change glutamate (glutamate plus glutamine relative to creatine) concentration in the striatum (p =.58; scaled Jeffreys-Zellner-Siow Bayes factor = 4.29). THC increased psychotic symptoms, but the severity of these symptoms was not correlated with striatal glutamate levels. Conclusions: These findings suggest that oral administration of 15 mg of THC does not result in altered striatal glutamate levels. Further work is needed to clarify the effects of THC on striatal glutamate

The impact of immediate breast reconstruction on the time to delivery of adjuvant therapy: the iBRA-2 study

Background: Immediate breast reconstruction (IBR) is routinely offered to improve quality-of-life for women requiring mastectomy, but there are concerns that more complex surgery may delay adjuvant oncological treatments and compromise long-term outcomes. High-quality evidence is lacking. The iBRA-2 study aimed to investigate the impact of IBR on time to adjuvant therapy. Methods: Consecutive women undergoing mastectomy ± IBR for breast cancer July–December, 2016 were included. Patient demographics, operative, oncological and complication data were collected. Time from last definitive cancer surgery to first adjuvant treatment for patients undergoing mastectomy ± IBR were compared and risk factors associated with delays explored. Results: A total of 2540 patients were recruited from 76 centres; 1008 (39.7%) underwent IBR (implant-only [n = 675, 26.6%]; pedicled flaps [n = 105,4.1%] and free-flaps [n = 228, 8.9%]). Complications requiring re-admission or re-operation were significantly more common in patients undergoing IBR than those receiving mastectomy. Adjuvant chemotherapy or radiotherapy was required by 1235 (48.6%) patients. No clinically significant differences were seen in time to adjuvant therapy between patient groups but major complications irrespective of surgery received were significantly associated with treatment delays. Conclusions: IBR does not result in clinically significant delays to adjuvant therapy, but post-operative complications are associated with treatment delays. Strategies to minimise complications, including careful patient selection, are required to improve outcomes for patients

Immune boosting by B.1.1.529 (Omicron) depends on previous SARS-CoV-2 exposure

The Omicron, or Pango lineage B.1.1.529, variant of SARS-CoV-2 carries multiple spike mutations with high transmissibility and partial neutralizing antibody (nAb) escape. Vaccinated individuals show protection from severe disease, often attributed to primed cellular immunity. We investigated T and B cell immunity against B.1.1.529 in triple mRNA vaccinated healthcare workers (HCW) with different SARS-CoV-2 infection histories. B and T cell immunity against previous variants of concern was enhanced in triple vaccinated individuals, but magnitude of T and B cell responses against B.1.1.529 spike protein was reduced. Immune imprinting by infection with the earlier B.1.1.7 (Alpha) variant resulted in less durable binding antibody against B.1.1.529. Previously infection-naïve HCW who became infected during the B.1.1.529 wave showed enhanced immunity against earlier variants, but reduced nAb potency and T cell responses against B.1.1.529 itself. Previous Wuhan Hu-1 infection abrogated T cell recognition and any enhanced cross-reactive neutralizing immunity on infection with B.1.1.529