Planning target volume margins for prostate radiotherapy using daily electronic portal imaging and implanted fiducial markers

<p>Abstract</p> <p>Background</p> <p>Fiducial markers and daily electronic portal imaging (EPI) can reduce the risk of geographic miss in prostate cancer radiotherapy. The purpose of this study was to estimate CTV to PTV margin requirements, without and with the use of this image guidance strategy.</p> <p>Methods</p> <p>46 patients underwent placement of 3 radio-opaque fiducial markers prior to prostate RT. Daily pre-treatment EPIs were taken, and isocenter placement errors were corrected if they were ≥ 3 mm along the left-right or superior-inferior axes, and/or ≥ 2 mm along the anterior-posterior axis. During-treatment EPIs were then obtained to estimate intra-fraction motion.</p> <p>Results</p> <p>Without image guidance, margins of 0.57 cm, 0.79 cm and 0.77 cm, along the left-right, superior-inferior and anterior-posterior axes respectively, are required to give 95% probability of complete CTV coverage each day. With the above image guidance strategy, these margins can be reduced to 0.36 cm, 0.37 cm and 0.37 cm respectively. Correction of all isocenter placement errors, regardless of size, would permit minimal additional reduction in margins.</p> <p>Conclusions</p> <p>Image guidance, using implanted fiducial markers and daily EPI, permits the use of narrower PTV margins without compromising coverage of the target, in the radiotherapy of prostate cancer.</p

Automated virtual reality therapy to treat agoraphobic avoidance and distress in patients with psychosis (gameChange): a multicentre, parallel-group, single-blind, randomised, controlled trial in England with mediation and moderation analyses

Background: Automated delivery of psychological therapy using immersive technologies such as virtual reality (VR) might greatly increase the availability of effective help for patients. We aimed to evaluate the efficacy of an automated VR cognitive therapy (gameChange) to treat avoidance and distress in patients with psychosis, and to analyse how and in whom it might work. // Methods: We did a parallel-group, single-blind, randomised, controlled trial across nine National Health Service trusts in England. Eligible patients were aged 16 years or older, with a clinical diagnosis of a schizophrenia spectrum disorder or an affective diagnosis with psychotic symptoms, and had self-reported difficulties going outside due to anxiety. Patients were randomly assigned (1:1) to either gameChange VR therapy plus usual care or usual care alone, using a permuted blocks algorithm with randomly varying block size, stratified by study site and service type. gameChange VR therapy was provided in approximately six sessions over 6 weeks. Trial assessors were masked to group allocation. Outcomes were assessed at 0, 6 (primary endpoint), and 26 weeks after randomisation. The primary outcome was avoidance of, and distress in, everyday situations, assessed using the self-reported Oxford Agoraphobic Avoidance Scale (O-AS). Outcome analyses were done in the intention-to-treat population (ie, all participants who were assigned to a study group for whom data were available). We performed planned mediation and moderation analyses to test the effects of gameChange VR therapy when added to usual care. This trial is registered with the ISRCTN registry, 17308399. // Findings: Between July 25, 2019, and May 7, 2021 (with a pause in recruitment from March 16, 2020, to Sept 14, 2020, due to COVID-19 pandemic restrictions), 551 patients were assessed for eligibility and 346 were enrolled. 231 (67%) patients were men and 111 (32%) were women, 294 (85%) were White, and the mean age was 37·2 years (SD 12·5). 174 patients were randomly assigned to the gameChange VR therapy group and 172 to the usual care alone group. Compared with the usual care alone group, the gameChange VR therapy group had significant reductions in agoraphobic avoidance (O-AS adjusted mean difference –0·47, 95% CI –0·88 to –0·06; n=320; Cohen's d –0·18; p=0·026) and distress (–4·33, –7·78 to –0·87; n=322; –0·26; p=0·014) at 6 weeks. Reductions in threat cognitions and within-situation defence behaviours mediated treatment outcomes. The greater the severity of anxious fears and avoidance, the greater the treatment benefits. There was no significant difference in the occurrence of serious adverse events between the gameChange VR therapy group (12 events in nine patients) and the usual care alone group (eight events in seven patients; p=0·37). // Interpretation: Automated VR therapy led to significant reductions in anxious avoidance of, and distress in, everyday situations compared with usual care alone. The mediation analysis indicated that the VR therapy worked in accordance with the cognitive model by reducing anxious thoughts and associated protective behaviours. The moderation analysis indicated that the VR therapy particularly benefited patients with severe agoraphobic avoidance, such as not being able to leave the home unaccompanied. gameChange VR therapy has the potential to increase the provision of effective psychological therapy for psychosis, particularly for patients who find it difficult to leave their home, visit local amenities, or use public transport. // Funding: National Institute of Health Research Invention for Innovation programme, National Institute of Health Research Oxford Health Biomedical Research Centre

Preoperative muscle weakness as defined by handgrip strength and postoperative outcomes: a systematic review

<p>Abstract</p> <p>Background</p> <p>Reduced muscle strength- commonly characterized by decreased handgrip strength compared to population norms- is associated with numerous untoward outcomes. Preoperative handgrip strength is a potentially attractive real-time, non-invasive, cheap and easy-to-perform "bedside" assessment tool. Using systematic review procedure, we investigated whether preoperative handgrip strength was associated with postoperative outcomes in adults undergoing surgery.</p> <p>Methods</p> <p>PRISMA and MOOSE consensus guidelines for reporting systematic reviews were followed. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Clinical Trials (1980-2010) were systematically searched by two independent reviewers. The selection criteria were limited to include studies of preoperative handgrip strength in human adults undergoing non-emergency, cardiac and non-cardiac surgery. Study procedural quality was analysed using the Newcastle-Ottawa Quality Assessment score. The outcomes assessed were postoperative morbidity, mortality and hospital stay.</p> <p>Results</p> <p>Nineteen clinical studies (17 prospective; 4 in urgent surgery) comprising 2194 patients were identified between1980-2010. Impaired handgrip strength and postoperative morbidity were defined inconsistently between studies. Only 2 studies explicitly ensured investigators collecting postoperative outcomes data were blinded to preoperative handgrip strength test results. The heterogeneity of study design used and the diversity of surgical procedures precluded formal meta-analysis. Despite the moderate quality of these observational studies, lower handgrip strength was associated with increased morbidity (n = 10 studies), mortality (n = 2/5 studies) and length of hospital stay (n = 3/7 studies).</p> <p>Conclusions</p> <p>Impaired preoperative handgrip strength may be associated with poorer postoperative outcomes, but further work exploring its predictive power is warranted using prospectively acquired, objectively defined measures of postoperative morbidity.</p

Hypofractionated radiotherapy for prostate cancer

In the last few years, hypofractionated external beam radiotherapy has gained increasing popularity for prostate cancer treatment, since sufficient evidence exists that prostate cancer has a low alpha/beta ratio, lower than the one of the surrounding organs at risk and thus there is a potential therapeutic benefit of using larger fractionated single doses. Apart from the therapeutic rationale there are advantages such as saving treatment time and medical resources and thereby improving patient's convenience. While older trials showed unsatisfactory results in both standard and hypofractionated arm due to insufficient radiation doses and non-standard contouring of target volumes, contemporary randomized studies have reported on encouraging results of tumor control mostly without an increase of relevant side effects, especially late toxicity. Aim of this review is to give a detailed analysis of relevant, recently published clinical trials with special focus on rationale for hypofractionation and different therapy settings

Predictors of mental health in female teachers

Objective: Teaching profession is characterised by an above-average rate of psychosomatic and mental health impairment due to work-related stress. The aim of the study was to identify predictors of mental health in female teachers. Material and Methods: A sample of 630 female teachers (average age 47±7 years) participated in a screening diagnostic inventory. Mental health was surveyed with the General Health Questionnaire GHQ-12. The following parameters were measured: specific work conditions (teacher-specific occupational history), scales of the Effort-Reward-Imbalance (ERI) Questionnaire as well as cardiovascular risk factors, physical complaints (BFB) and personal factors such as inability to recover (FABA), sense of coherence (SOC) and health behaviour. Results: First, mentally fit (MH+) and mentally impaired teachers (MH-) were differentiated based on the GHQ-12 sum score (MH+: < 5; MH-: ≥ 5); 18% of the teachers showed evidence of mental impairment. There were no differences concerning work-related and cardiovascular risk factors as well as health behaviour between MH+ and MH-. Binary logistic regressions identified 4 predictors that showed a significant effect on mental health. The effort-reward-ratio proved to be the most relevant predictor, while physical complaints as well as inability to recover and sense of coherence were identified as advanced predictors (explanation of variance: 23%). Conclusion: Contrary to the expectations, classic work-related factors can hardly contribute to the explanation of mental health. Additionally, cardiovascular risk factors and health behaviour have no relevant influence. However, effort-reward-ratio, physical complaints and personal factors are of considerable influence on mental health in teachers. These relevant predictors should become a part of preventive arrangements for the conservation of teachers' health in the future

Li1.5La1.5MO6 (M = W6+, Te6+) as a new series of lithium-rich double perovskites for all-solid-state lithium-ion batteries

Solid-state batteries are a proposed route to safely achieving high energy densities, yet this architecture faces challenges arising from interfacial issues between the electrode and solid electrolyte. Here we develop a novel family of double perovskites, Li1.5La1.5MO6 (M = W6+, Te6+), where an uncommon lithium-ion distribution enables macroscopic ion diffusion and tailored design of the composition allows us to switch functionality to either a negative electrode or a solid electrolyte. Introduction of tungsten allows reversible lithium-ion intercalation below 1 V, enabling application as an anode (initial specific capacity >200 mAh g-1 with remarkably low volume change of ∼0.2%). By contrast, substitution of tungsten with tellurium induces redox stability, directing the functionality of the perovskite towards a solid-state electrolyte with electrochemical stability up to 5 V and a low activation energy barrier (<0.2 eV) for microscopic lithium-ion diffusion. Characterisation across multiple length- and time-scales allows interrogation of the structure-property relationships in these materials and preliminary examination of a solid-state cell employing both compositions suggests lattice-matching avenues show promise for all-solid-state batteries

PANC Study (Pancreatitis: A National Cohort Study): national cohort study examining the first 30 days from presentation of acute pancreatitis in the UK

Background Acute pancreatitis is a common, yet complex, emergency surgical presentation. Multiple guidelines exist and management can vary significantly. The aim of this first UK, multicentre, prospective cohort study was to assess the variation in management of acute pancreatitis to guide resource planning and optimize treatment. Methods All patients aged greater than or equal to 18 years presenting with acute pancreatitis, as per the Atlanta criteria, from March to April 2021 were eligible for inclusion and followed up for 30 days. Anonymized data were uploaded to a secure electronic database in line with local governance approvals. Results A total of 113 hospitals contributed data on 2580 patients, with an equal sex distribution and a mean age of 57 years. The aetiology was gallstones in 50.6 per cent, with idiopathic the next most common (22.4 per cent). In addition to the 7.6 per cent with a diagnosis of chronic pancreatitis, 20.1 per cent of patients had a previous episode of acute pancreatitis. One in 20 patients were classed as having severe pancreatitis, as per the Atlanta criteria. The overall mortality rate was 2.3 per cent at 30 days, but rose to one in three in the severe group. Predictors of death included male sex, increased age, and frailty; previous acute pancreatitis and gallstones as aetiologies were protective. Smoking status and body mass index did not affect death. Conclusion Most patients presenting with acute pancreatitis have a mild, self-limiting disease. Rates of patients with idiopathic pancreatitis are high. Recurrent attacks of pancreatitis are common, but are likely to have reduced risk of death on subsequent admissions

Molecular analysis of human leukocyte antigen class I and class II allele frequencies and haplotype distribution in Pakistani population

Aim: Distribution of HLA class I and II alleles and haplotype was studied in Pakistani population and compared with the data reported for Caucasoid, Africans, Orientals and Arab populations. Materials and Methods: HLA class I and II polymorphisms in 1000 unrelated Pakistani individuals was studied using sequence-specific primers and polymerase chain reaction and assay. Results: The most frequent class I alleles observed were AFNx0102, BFNx0135 and CwFNx0107, with frequencies of 19.2, 13.7 and 20%, respectively. Fifteen distinct HLA-DRB1 alleles and eight HLA-DQB1 alleles were recognized. The most frequently observed DRB1 alleles which represented more than 60% of the subjects were DRB1 FNx0103, FNx0107, FNx0111 and FNx0115. The rare DRB1 alleles detected in this study were HLADRB1 FNx0108 and FNx0109, having frequencies of 0.9 and 1.7%, respectively. In addition, at DRB1-DQB1 loci there were 179 different haplotypes and 285 unique genotypes and the most common haplotype was DRB1FNx0115-DQB1FNx0106 which represented 17% of the total DRB1-DQB1 haplotypes. In our population, haplotype AFNx0133-BFNx0158-CwFNx0103 comprised 2.8% of the total class I haplotypes observed. This haplotype was seen only in the oriental populations and has not been reported in the African or European Caucasoid. Conclusion: Our study showed a close similarity of HLA class I and II alleles with that of European Caucasoid and Orientals. In Pakistani population, two rare loci and three haplotypes were identified, whereas haplotypes characteristic of Caucasians, Africans and Orientals were also found, suggesting an admixture of different races due to migration to and from this region