One-year costs of bilateral or single internal mammary grafts in the Arterial Revascularisation Trial

Objective: Coronary artery bypass grafting (CABG) using bilateral internal mammary arteries (BIMA) may improve survival over CABG using single internal mammary arteries (SIMA), but may be surgically more complex (and therefore costly) and associated with impaired sternal wound healing. We report, for the first time, a detailed comparison of healthcare resource use and costs over 12 months, as part of the Arterial Revascularisation (ART) Trial.  Methods: 3102 patients in 28 hospitals in seven countries were randomised to CABG surgery using BIMA (n=1548) or SIMA (n=1554). Detailed resource use data were collected covering surgery, the initial hospital episode, and for 12 months post randomisation. Using UK unit costs, total costs were calculated and compared between trial arms and for subgroups.  Results: Patients randomised to BIMA spent 20 min longer in theatre (95% CI 15 to 25, p<0.001) and also required more treatment for sternal wound problems. Mean (SD) total costs per patient at 12 months were £13 839 (£10 534) for BIMA and £12 717 (£9719) for SIMA (mean cost difference £1122, 95% CI £407 to £1838, p=0.002). No tests for interaction between subgroups and treatment allocation were significant.  Conclusions: At 12 months from randomisation, mean costs were approximately 9% higher in BIMA than SIMA patients, primarily due to longer time in theatre and in-hospital stay, and slightly higher costs related to sternal wound problems during follow-up. Follow-up to the primary trial endpoint of 10 years will reveal whether longer-term differences emerge in graft patency or in overall survival

Efficacy of personalized cognitive counseling in men of color who have sex with men: secondary data analysis from a controlled intervention trial.

In a previous report, we demonstrated the efficacy of a cognitively based counseling intervention compared to standard counseling at reducing episodes of unprotected anal intercourse (UAI) among men who have sex with men (MSM) seeking HIV testing. Given the limited number of efficacious prevention interventions for MSM of color (MOC) available, we analyzed the data stratified into MOC and whites. The sample included 196 white MSM and 109 MOC (23 African Americans, 36 Latinos, 22 Asians, eight Alaskan Natives/Native Americans/Hawaiian/Pacific Islander, and 20 of mixed or other unspecified race). Among MOC in the intervention group, the mean number of episodes of UAI declined from 5.1 to 1.6 at six months and was stable at 12 months (1.8). Among the MOC receiving standard counseling, the mean number of UAI episodes was 4.2 at baseline, 3.9 at six months and 2.1 at 12 months. There was a significant treatment effect overall (relative risk 0.59, 95% confidence interval 0.35-0.998). These results suggest that the intervention is effective in MOC

Detailed characterization of a long-term rodent model of critical illness and recovery

Objective: To characterize a long-term model of recovery from critical illness, with particular emphasis on cardiorespiratory, metabolic, and muscle function. Design: Randomized controlled animal study. Setting: University research laboratory. Subjects: Male Wistar rats. Interventions: Intraperitoneal injection of the fungal cell wall constituent, zymosan or n-saline. Measurements and Main Results: Following intervention, rats were followed for up to 2 weeks. Animals with zymosan peritonitis reached a clinical and biochemical nadir on day 2. Initial reductions were seen in body weight, total body protein and fat, and muscle mass. Leg muscle fiber diameter remained subnormal at 14 days with evidence of persisting myonecrosis, even though gene expression of regulators of muscle mass (e.g., MAFbx, MURF1, and myostatin) had peaked on days 2–4 but normalized by day 7. Treadmill exercise capacity, forelimb grip strength, and in vivo maximum tetanic force were also reduced. Food intake was minimal until day 4 but increased thereafter. This did not relate to appetite hormone levels with early (6 hr) rises in plasma insulin and leptin followed by persisting subnormal levels; ghrelin levels did not change. Serum interleukin-6 level peaked at 6 hours but had normalized by day 2, whereas interleukin-10 remained persistently elevated and high-density lipoprotein cholesterol persistently depressed. There was an early myocardial depression and rise in core temperature, yet reduced oxygen consumption and respiratory exchange ratio with a loss of diurnal rhythmicity that showed a gradual but incomplete recovery by day 7. Conclusions: This detailed physiological, metabolic, hormonal, functional, and histological muscle characterization of a model of critical illness and recovery reproduces many of the findings reported in human critical illness. It can be used to assess putative therapies that may attenuate loss, or enhance recovery, of muscle mass and function

Is Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography Imaging Cost-effective in Prostate Cancer: An Analysis Informed by the proPSMA Trial.

BackgroundBefore integrating prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) into routine care, it is important to assess if the benefits justify the differences in resource use.ObjectiveTo determine the cost-effectiveness of PSMA-PET/CT when compared with conventional imaging.Design, setting, and participantsA cost-effectiveness analysis was developed using data from the proPSMA study. proPSMA included patients with high-risk prostate cancer assigned to conventional imaging or 68Ga-PSMA-11 PET/CT with planned health economics data collected. The cost-effectiveness analysis was conducted from an Australian societal perspective.Intervention68Ga-PSMA-11 PET/CT compared with conventional imaging (CT and bone scan).Outcome measurements and statistical analysisThe primary outcome from proPSMA was diagnostic accuracy (nodal and distant metastases). This informed a decision tree analysis of the cost per accurate diagnosis.Results and limitationsThe estimated cost per scan for PSMA PET/CT was AUD$1203, which was less than the conventional imaging cost at AUD$1412. PSMA PET/CT was thus dominant, having both better accuracy and a lower cost. This resulted in a cost of AUD$959 saved per additional accurate detection of nodal disease, and AUD$1412 saved for additional accurate detection of distant metastases. The results were most sensitive to variations in the number of men scanned for each 68Ga-PSMA-11 production run. Subsequent research is required to assess the long-term costs and benefits of PSMA PET/CT-directed care.ConclusionsPSMA PET/CT has lower direct comparative costs and greater accuracy compared to conventional imaging for initial staging of men with high-risk prostate cancer. This provides a compelling case for adopting PSMA PET/CT into clinical practice.Patient summaryThe proPSMA study demonstrated that prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) better detects disease that has spread beyond the prostate compared with conventional imaging. Our analysis shows that PSMA PET/CT is also less costly than conventional imaging for the detection of disease spread. This research was presented at the European Association of Nuclear Medicine Scientific Meeting in October 2020

A randomised controlled trial of adjunctive triamcinolone acetonide in eyes undergoing vitreoretinal surgery for open globe trauma – the ASCOT study

Background: Eyes sustaining open globe trauma are at high risk of severe visual impairment. Proliferative vitreoretinopathy is the most common cause of retinal detachment and visual loss in eyes with open globe trauma. There is evidence from experimental studies and pilot clinical trials that the use of adjunctive steroid medication triamcinolone acetonide can reduce the incidence of proliferative vitreoretinopathy and improve outcomes of surgery for open globe trauma. Objective: The Adjunctive Steroid Combination in Ocular Trauma or ASCOT study aimed to investigate the clinical effectiveness of adjunctive triamcinolone acetonide given at the time of vitreoretinal surgery for open globe trauma. Design: A phase 3 multicentre double-masked randomised controlled trial randomising patients undergoing vitrectomy following open globe trauma to either adjunctive triamcinolone acetonide or standard care. Setting: Hospital vitreoretinal surgical services dealing with open globe trauma. Participants: Patients undergoing vitrectomy surgery who had sustained open globe trauma. Interventions: Triamcinolone acetonide 4 mg/0.1 ml into the vitreous cavity and 40 mg/1 ml sub-Tenon’s or standard vitreoretinal surgery and postoperative care. Main outcome measures: The primary outcome was the proportion of patients with at least 10 letters of improvement in corrected visual acuity at six months. Secondary outcomes included retinal detachment secondary to proliferative vitreoretinopathy, retinal reattachment, macula reattachment, tractional retinal detachment, number of operations, hypotony, elevated intraocular pressure and quality of life. Health-related quality of life was assessed using the EuroQol Five Domain and Visual Function Questionnaire 25 questionnaires.Results: A total of 280 patients were randomised; 129 were analysed from the control group and 130 from the treatment group. The treatment group appeared, by chance, to have more severe pathology on presentation. The primary outcome (improvement in visual acuity) and principal secondary outcome (change in visual acuity) did not demonstrate any treatment benefit for triamcinolone acetonide. The proportion of patients with improvement in visual acuity was 47% for triamcinolone acetonide and 43% for standard care (odds ratio 1.03, 95% confidence interval 0.61 to 1.75, p = 0.908); the baseline adjusted mean difference in the six-month change in visual acuity was –2.65 (95% confidence interval –9.22 to 3.92, p = 0.430) for triamcinolone acetonide relative to control. Similarly, the secondary outcome measures failed to show any treatment benefit. For two of the secondary outcome measures, stable complete retinal reattachment and stable macular retinal reattachment, outcomes for the treatment group were significantly worse for triamcinolone acetonide at the 5% level (respectively, odds ratio 0.59, 95% confidence interval 0.36 to 0.99, p = 0.044 and odds ratio 0.59, 95% confidence interval 0.35 to 0.98, p = 0.041) compared with control in favour of control. The cost of the intervention was £132 per patient. Health economics outcome measures (Early Treatment Diabetic Retinopathy Study, Visual Function Questionnaire 25 and EuroQol Five Dimensions) did not demonstrate any significant difference in quality-adjusted life-years. Conclusions: The use of combined intraocular and sub-Tenon’s capsule triamcinolone acetonide is not recommended as an adjunct to vitrectomy surgery for intraocular trauma. Secondary outcome measures are suggestive of a negative effect of the adjunct, although the treatment group appeared to have more severe pathology on presentation

Cognitive behaviour therapy versus counselling intervention for anxiety in young people with high-functioning autism spectrum disorders: a pilot randomised controlled trial

The use of cognitive-behavioural therapy (CBT) as a treatment for children and adolescents with autism spectrum disorder (ASD) has been explored in a number of trials. Whilst CBT appears superior to no treatment or treatment as usual, few studies have assessed CBT against a control group receiving an alternative therapy. Our randomised controlled trial compared use of CBT against person-centred counselling for anxiety in 36 young people with ASD, ages 12–18. Outcome measures included parent- teacher- and self-reports of anxiety and social disability. Whilst each therapy produced improvements inparticipants, neither therapy was superior to the other to a significant degree on any measure. This is consistent with findings for adults

Perspectives on the Social, Physical and Emotional Impact of Living with Perthes’ Disease in Children and their Family: a Mixed Methods Study.

Aim: To determine the social, physical and emotional impact of living with Perthes’ disease on affected children and their family (caregivers). Patients and Methods: Through a mixed methods approach, we interviewed 18 parents and explored the perspectives of 12 children affected by Perthes’ disease (mean 7.1 years, SD±4.1 years) using a survey tool. Thematic analysis of parents’ interviews provided an insight into disease-specific factors influencing patients and family’s daily life activities. Using the childhood survey tool, good and bad day scores were analyzed using MANOVA. Results: Thematic analysis of the parent interviews (main themes n=4) identified a marked effect of the disease on many facets of the child’s life, particularly pain and the impact on sleep, play and school attendance. In addition, the interviews identified a negative effect on the family life of the parents and siblings. Children indicated that activities of daily living were affected even during ‘good days’ (p<0.05) but pain was the key limiting factor. Conclusion: Perthes’ disease negatively affects the social, physical and emotional well-being of children and their family. These findings provide outcome domains that are important to measure in day-to-day care and add in-depth insight into the challenges caused by this disease for health care professionals involved in clinical management

Social anxiety in adult males with autism spectrum disorders

Background: Psychiatric conditions, notably anxiety, commonly co-occur with autism spectrum disorders (ASD). Method: This study investigated self-reported behavioural, cognitive and affective symptoms of social anxiety (SA) in 50 adult males with ASD. Associations between SA, core ASD symptoms and facets of neuropsychological functioning were also examined. Results: Twenty-six participants (52%) endorsed levels of SA that exceeded the suggested caseness threshold for social anxiety disorder. Categorical and dimensional data analyses indicated that there were no relationships between SA symptoms, present-state or childhood ASD symptom-severity, or measures of socio-emotional processing in this sample. Conclusions: Study findings suggest that severity of SA is not merely a reflection of ASD symptom-severity. Further research is needed to ascertain the prevalence of SA in adult ASD epidemiological samples, and identify causal and maintaining mechanisms for these co-morbid symptoms

Predicting the diagnosis of autism in adults using the Autism-Spectrum Quotient (AQ) questionnaire

This work was supported by a National Institute for Health Research (NIHR) programme grant (RP-PG-0606-1045), by the BGC as well as by the European Union via the EU-AIMS consortium. J.H. was supported by the Wellcome Trust and by the Biomedical Research Centre (BRC) at King's College London. D.G.M was supported by the Dr Mortimer D. Sackler Foundation. P.B was supported by an NIHR Senior Investigator award and the BRC in Mental Health at the South London and Maudsley NHS Trust. C.E.W receives postdoctoral research funding via the Marie Curie Action, co-financed by the Junta de Andalucía and the European Commission under Talentia Postdoc grant number 267 226. The authors acknowledge financial support from the Department of Health via the NIHR BRC and Dementia Unit awarded to South London and Maudsley NHS Foundation Trust, in partnership with King's College London and King's College Hospital NHS Foundation Trust. This work was supported by EU-AIMS (European Autism Interventions), which receives support from the Innovative Medicines Initiative Joint Undertaking under grant agreement no. 115300, the resources of which are composed of financial contributions from the European Union's Seventh Framework Programme (grant FP7/2007-2013), from the European Federation of Pharmaceutical Industries and Associations companies’ in-kind contributions, and from Autism Speaks

A dynastic elite in monumental Neolithic society

The nature and distribution of political power in Europe during the Neolithic era remains poorly understood. During this period, many societies began to invest heavily in building monuments, which suggests an increase in social organization. The scale and sophistication of megalithic architecture along the Atlantic seaboard, culminating in the great passage tomb complexes, is particularly impressive. Although co-operative ideology has often been emphasised as a driver of megalith construction, the human expenditure required to erect the largest monuments has led some researchers to emphasize hierarchy—of which the most extreme case is a small elite marshalling the labour of the masses. Here we present evidence that a social stratum of this type was established during the Neolithic period in Ireland. We sampled 44 whole genomes, among which we identify the adult son of a first-degree incestuous union from remains that were discovered within the most elaborate recess of the Newgrange passage tomb. Socially sanctioned matings of this nature are very rare, and are documented almost exclusively among politico-religious elites—specifically within polygynous and patrilineal royal families that are headed by god-kings. We identify relatives of this individual within two other major complexes of passage tombs 150 km to the west of Newgrange, as well as dietary differences and fine-scale haplotypic structure (which is unprecedented in resolution for a prehistoric population) between passage tomb samples and the larger dataset, which together imply hierarchy. This elite emerged against a backdrop of rapid maritime colonization that displaced a unique Mesolithic isolate population, although we also detected rare Irish hunter-gatherer introgression within the Neolithic population