Search

Background PT027 is a fixed-dose combination of albuterol (salbutamol) and budesonide in a single pressurized metered dose inhaler. Objective To assess the efficacy and safety of albuterol/budesonide compared with placebo in patients with asthma and exercise-induced bronchoconstriction (EIB). Methods In this randomized, double-blind, 2-period, single-dose crossover study, adolescents and adults with asthma and EIB (defined by ≥20% decrease from pre-exercise challenge FEV 1) were randomized to albuterol/budesonide (180/160 µg) followed by placebo (n=29) or the reverse sequence (n=31). Subjects were stratified by background therapy (as-needed short-acting β 2 -agonist [SABA] alone or low- to medium-dose inhaled corticosteroid [ICS] plus as-needed SABA). FEV 1 was measured 5 minutes pre-dose, 30 minutes post-dose (5 minutes pre-exercise challenge [baseline]), and 5, 10, 15, 30 and 60 minutes post-exercise. The primary endpoint was maximum percentage fall from baseline in FEV 1 up to 60 minutes postexercise challenge. Results Least squares mean maximum percentage fall in FEV 1 up to 60 minutes postexercise challenge was 5.45% with albuterol/budesonide versus 18.97% with placebo (difference -13.51% [95% CI: -16.94%, -10.09%]; p Conclusion In adolescents and adults with asthma and EIB, a single dose of albuterol/budesonide 180/160 µg taken approximately 30 minutes prior to exercise was significantly more effective than placebo in preventing EIB.

Aims To analyse dosimetric and clinical predictors for acute and late gastrointestinal toxicity following chemoradiotherapy of anal cancer. Materials and methods Consecutive patients with locally advanced (T2 ≥4 cm - T4 or N+) anal cancer were selected from an institutional database (n = 114). All received intensity-modulated radiotherapy with concomitant 5-fluorouracil and mitomycin C. Gastrointestinal toxicity was retrospectively graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 and bowel cavity, small bowel and large bowel were contoured. Dosimetric and clinical variables were tested for associations with acute grade ≥3 gastrointestinal toxicity and late grade ≥2 gastrointestinal toxicity using the Mann-Whitney test, area under receiver operating characteristic curve (AUC) and logistic regression. Results The median follow-up was 40 months. Acute grade ≥3 gastrointestinal toxicity was seen in 51 (44.7%) of the patients; late grade ≥2 gastrointestinal toxicity was seen in 36 of the patients (39.6% of 91 patients with >1 year recurrence-free follow-up). Bowel cavity V30Gy was the best dosimetric predictor for acute gastrointestinal toxicity (AUC 0.633; P = 0.02). Large bowel V20Gy was the best dosimetric predictor for late gastrointestinal toxicity (AUC 0.698; P = 0.001) but showed no association with acute gastrointestinal toxicity. In multivariate logistic regression, increasing age was significantly associated with acute gastrointestinal toxicity; smoking and large bowel V20Gy were significantly associated with late gastrointestinal toxicity. Patients who experienced acute grade ≥3 gastrointestinal toxicity were not at an increased risk of late grade ≥2 gastrointestinal toxicity (odds ratio 1.3; P = 0.55). Conclusions Factors of importance for acute and late gastrointestinal toxicity were not the same. Bowel cavity V30Gy is a good metric to use for the prediction of acute gastrointestinal toxicity, but the results of our study indicate that individual large and small bowel loops need to be contoured for better prediction of late gastrointestinal toxicity. The role of the large bowel as an important organ at risk for late gastrointestinal toxicity merits further research.

Background: Our objective is to describe our pediatric virtual urgent care (VUC) experience at a large urban academic medical center, in response to the COVID-19 pandemic in New York City (NYC). Materials and Methods: We conducted a retrospective cohort study of our pediatric VUC program of patients less than age 18 years, from March 1 to May 31, 2020. We include data on expansion of staffing, patient demographics, virtual care, and outcomes. Results: We rapidly onboarded, educated, and trained pediatric telemedicine providers. We evaluated 406 pediatric patients with median age 4.4 years and 53.9% male. Median call time was 5:12 pm, median time to provider was 5.7 min, and median duration of call was 11.1 min. The most common reasons for a visit were COVID-19-related symptoms (36%), dermatologic (15%), and trauma (10%). Virtual care for patients consisted of conservative management (72%), medication prescription (18%), and referral to an urgent care or pediatric emergency department (PED) (10%). Of 16 patients referred and presented to our emergency department, 2 required intensive care for multisystem inflammatory syndrome in children. Oral antibiotics were prescribed for 7.1% of all patients. Only 0.005% of patients had an unplanned 72-h PED visit resulting in hospitalization after a VUC visit. Conclusion: Pediatric emergency VUC allowed for high-quality efficient medical care for patients during the peak of the COVID-19 pandemic in NYC. Although most patients were managed conservatively in their home, telemedicine also enabled rapid identification of patients who required in-person emergency care.

Purpose The application of automated image analyses could improve and facilitate standardization and consistency of quantification in [18F]DCFPyL (PSMA) PET/CT scans. In the current study, we analytically validated aPROMISE, a software as a medical device that segments organs in low-dose CT images with deep learning, and subsequently detects and quantifies potential pathological lesions in PSMA PET/CT. Methods To evaluate the deep learning algorithm, the automated segmentations of the low-dose CT component of PSMA PET/CT scans from 20 patients were compared to manual segmentations. Dice scores were used to quantify the similarities between the automated and manual segmentations. Next, the automated quantification of tracer uptake in the reference organs and detection and pre-segmentation of potential lesions were evaluated in 339 patients with prostate cancer, who were all enrolled in the phase II/III OSPREY study. Three nuclear medicine physicians performed the retrospective independent reads of OSPREY images with aPROMISE. Quantitative consistency was assessed by the pairwise Pearson correlations and standard deviation between the readers and aPROMISE. The sensitivity of detection and pre-segmentation of potential lesions was evaluated by determining the percent of manually selected abnormal lesions that were automatically detected by aPROMISE. Results The Dice scores for bone segmentations ranged from 0.88 to 0.95. The Dice scores of the PSMA PET/CT reference organs, thoracic aorta and liver, were 0.89 and 0.97, respectively. Dice scores of other visceral organs, including prostate, were observed to be above 0.79. The Pearson correlation for blood pool reference was higher between any manual reader and aPROMISE, than between any pair of manual readers. The standard deviations of reference organ uptake across all patients as determined by aPROMISE (SD = 0.21 blood pool and SD = 1.16 liver) were lower compared to those of the manual readers. Finally, the sensitivity of aPROMISE detection and pre-segmentation was 91.5% for regional lymph nodes, 90.6% for all lymph nodes, and 86.7% for bone in metastatic patients. Conclusion In this analytical study, we demonstrated the segmentation accuracy of the deep learning algorithm, the consistency in quantitative assessment across multiple readers, and the high sensitivity in detecting potential lesions. The study provides a foundational framework for clinical evaluation of aPROMISE in standardized reporting of PSMA PET/CT.

The mammalian brain develops through a complex interplay of spatial cues generated by diffusible morphogens, cell–cell interactions and intrinsic genetic programs that result in probably more than a thousand distinct cell types. A complete understanding of this process requires a systematic characterization of cell states over the entire spatiotemporal range of brain development. The ability of single-cell RNA sequencing and spatial transcriptomics to reveal the molecular heterogeneity of complex tissues has therefore been particularly powerful in the nervous system. Previous studies have explored development in specific brain regions1–8, the whole adult brain9 and even entire embryos10. Here we report a comprehensive single-cell transcriptomic atlas of the embryonic mouse brain between gastrulation and birth. We identified almost eight hundred cellular states that describe a developmental program for the functional elements of the brain and its enclosing membranes, including the early neuroepithelium, region-specific secondary organizers, and both neurogenic and gliogenic progenitors. We also used in situ mRNA sequencing to map the spatial expression patterns of key developmental genes. Integrating the in situ data with our single-cell clusters revealed the precise spatial organization of neural progenitors during the patterning of the nervous system. A comprehensive single-cell transcriptomic atlas of the mouse brain between gastrulation and birth identifies hundreds of cellular states and reveals the spatiotemporal organization of brain development.

Rationale: Standardized staging and quantitative reporting is necessary to demonstrate the association of 18F-DCFPyL PET/CT (PSMA) imaging with clinical outcome. This work introduces an automated platform to implement and extend the Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE) criteria - aPROMISE. The objective is to validate the performance of aPROMISE in staging and quantifying disease burden in patients with prostate cancer who undergo PSMA Imaging. Methods: This was a retrospective analysis of 109 Veterans with intermediate and high-risk prostate cancer, who underwent PSMA imaging. To validate the performance of aPROMISE, two independent nuclear-medicine physicians conducted aPROMISE-assisted reads, resulting in standardized reports that quantify individual lesions and stage the patients. Patients were staged as having local only disease (miN0M0); regional lymph node only (miN1M0), metastatic disease only (miN0M1), and with both regional and distant metastatic disease (miN1M1). The staging obtained from aPROMISE-assisted reads was compared with the staging by conventional imaging. Cohen's pairwise kappa agreement was used to evaluate the inter-reader variability. Correlation coefficient and ICC was used to evaluate the inter-reader variability of the quantitative assessment (miPSMA-index) in each stage. Kendall Tau and t-test was used to evaluate the association of miPSMA-index with PSA and Gleason Score. Results: All PSMA images of 109 veterans met the DICOM conformity and the requirements for the aPROMISE analysis. Both independent aPROMISE-assisted analyses demonstrated significant upstaging in patients with localized (23%; N = 20/87) and regional tumor burden (25%; N = 2/8). However, a significant number of patients with bone metastases identified on conventional imaging (NaF PET/CT) were downstaged (29%; N = 4/14). The comparison of the two independent aPROMISE-assisted reads demonstrated a high kappa agreement - 0.82 (miN0M0), 0.90 (miN1M0), and 0.77 (miN0M1). The Spearman correlation of quantitative miPSMA-index was 0.93, 0.96 and 0.97, respectively. As a continuous variable, miPSMA index in the prostate (miT) was associated with risk groups defined by the PSA and Gleason.. Conclusion: Here we demonstrate consistency of the aPROMISE platform between readers and observed substantial upstaging in PSMA imaging compared to the conventional imaging. aPROMISE may contribute to the broader standardization of PSMA imaging assessment and to its clinical utility in management of prostate cancer patients.

PurposeTo evaluate two chest tomosynthesis (CTS) scoring systems for cystic fibrosis (CF), one system developed by Vult von Steyern et al. (VvS) and one system based on the Brody scoring system for high-resolution computed tomography (HRCT) (modified Brody (mB)). Brody scoring of HRCT was used as reference.MethodsIn conjunction with routine control HRCT at clinical follow-up, 10 consecutive adult CF patients underwent CTS for research purposes. Four radiologists scored the CTS examinations using the mB and VvS scoring systems. All scores were compared to the Brody HRCT scores. The agreement between the evaluated CTS scoring systems and the reference HRCT scoring system was determined using Spearman’s rank correlation coefficient and the intraclass correlation coefficient (ICC).Major findingsSpearman’s rank correlation coefficient showed strong correlations between HRCT score and both the mB and the VvS CTS total scores (median rs = 0.81 and 0.85, respectively). The ICC showed strong correlation between the CTS scoring systems and the reference: 0.88 for mB and 0.85 for VvS scoring. The median time for scoring was 20 and 10 minutes for the mB and VvS scoring systems, respectively.ConclusionsBoth evaluated CTS scoring systems correlate well with the reference standard Brody HRCT scoring. The VvS CTS scoring system has a shorter reading time, suggesting its advantage in clinical practice.

Access to timely behaviour support services for children and adolescents with a disability in rural and remote regions of Australia is problematic due to the inadequate supply of specialised staff ...

In contrast to optical colonoscopy, computed tomography colonography (CTC) has the ability to reveal pathology outside of the colon. While identification of colorectal lesions at CTC requires only limited radiation dose, the detection of abnormalities in extracolonic soft tissue requires more radiation. The purpose of this study was to investigate the influence of ultra-low-dose (ULD) CTC on the detection and characterisation of extracolonic findings. In a prospective study 49 patients with colorectal symptoms were examined with CTC adding a ULD series (mean effective dose 0.9 ± 0.4 mSv) to the normal unenhanced standard dose (SD) series (mean effective dose 3.6 ± 1.2 mSv). Five radiologists individually and blindly evaluated the ULD, followed by evaluation of the SD after ≥9 weeks (median 35 weeks). A ViewDEX-based examination protocol was used, including a confidence scale and a graded assessment of need for follow-up according to the CTC Reporting and Data System (C-RADS E0–E4). The reference findings comprised the combined information from CTC (ULD, SD and contrast-enhanced CTC series) and a 4-year radiological and clinical follow-up. For the overall detection of reference findings (E2–E4) we found a statistically significant difference in favour of SD. This, however, was not the case when looking at classification of possibly important/important reference findings (E3–E4). Our results suggest that CTC with ULD (0.9 mSv) is comparable to SD (3.6 mSv) for identification of clinically relevant extracolonic pathology, but there is a large inter-observer variability.

Young adult drinkers engage in a range of drinking patterns from abstaining to heavy drinking in both the United States and Sweden. Heavy drinking during young adulthood in both countries is associated with a variety of negative consequences. Personalized feedback interventions have been identified as effective prevention strategies to prevent or reduce heavy drinking in the United States. This study examined transitions in drinking profiles and compared the efficacy of a personalized feedback intervention for 3965 young adults in the United States (1,735) and Sweden (2230) during their transition out of high school. Using goodness-of-fit criteria, results indicated that three drinking profiles exist among young adults transitioning out of high school: very low drinkers/abstainers, moderate to heavy drinkers, and very heavy drinkers. Latent Markov models revealed a moderating effect of country on personalized feedback intervention such that intervention condition participants in the United States were more likely to belong to the light drinker/abstainer or moderate to heavy profile relative to the very heavy drinking profile at 6-month follow-up. There was no significant effect of personalized feedback intervention in Sweden. Future research could investigate the impact of when personalized feedback interventions are administered and could examine if personalized feedback interventions should be more intentionally culturally adapted in order to be more effective.

Rationale & Objective Hyperuricemia has been implicated in the development and progression of chronic kidney disease. Verinurad is a novel, potent, specific urate reabsorption inhibitor. We evaluated the effects on albuminuria of intensive urate-lowering therapy with verinurad combined with the xanthine oxidase inhibitor febuxostat in patients with hyperuricemia and type 2 diabetes mellitus (T2DM). Study Design Phase 2, multicenter, prospective, randomized, double-blind, parallel-group, placebo-controlled trial. Setting & Participants Patients 18 years or older with hyperuricemia, albuminuria, and T2DM. Intervention Patients randomly assigned 1:1 to verinurad (9mg) plus febuxostat (80mg) or matched placebo once daily for 24 weeks. Outcomes The primary end point was change in urinary albumin-creatinine ratio (UACR) from baseline after 12 weeks' treatment. Secondary end points included safety and tolerability and effect on glomerular filtration. Results 60 patients were enrolled (n=32, verinurad and febuxostat; n=28, placebo). UACRs after treatment with verinurad plus febuxostat were lower than after placebo at 1, 12, and 24 weeks: −38.6% (90% CI, −60.9% to−3.6%), −39.4% (90% CI, −61.8% to−3.8%), and−49.3% (90% CI, −68.2% to−19.0%), respectively. Serum urate levels after treatment with verinurad plus febuxostat were 59.6% and 63.7% lower than after placebo at 12 and 24 weeks, respectively. No clinically meaningful changes were observed in estimated glomerular filtration rate or serum creatinine or serum cystatin C concentrations. Verinurad plus febuxostat was well tolerated. Limitations Sample size and study duration were insufficient to evaluate definitive effects of verinurad plus febuxostat on UACR and glomerular filtration. Generalizability was limited by exclusion of patients with stages 4 and 5 chronic kidney disease. Conclusions Verinurad plus febuxostat reduced albuminuria and lowered serum urate concentrations in patients with T2DM, albuminuria, and hyperuricemia. Definitive assessment of their combined impact on preservation of kidney function awaits larger clinical studies. Funding This study was supported by AstraZeneca. Trial Registration Registered at ClinicalTrials.gov with study number NCT03118739.

Purpose: Digital tomosynthesis (DTS) is currently undergoing validation for potential clinical implications. The aim of this study was to investigate the potential for DTS as a low-dose alternative to computed tomography (CT) in imaging of pulmonary pathology in patients with cystic fibrosis (CF). Methods: DTS and CT were performed as part of the routine triannual follow-up in 31 CF patients. Extent of disease was quantified according to modality-specific scoring systems. Statistical analysis included Spearman’s rank correlation coefficient (r) and Krippendorff’s alpha (α). Major findings: The median effective dose was 0.14 for DTS and 2.68 for CT. Intermodality correlation was very strong for total score and the subscores regarding bronchiectasis and bronchial wall-thickening (r = 0.82–0.91, P

Introduction: The aim of this study was to obtain expert consensus on the content of a curriculum for learning chorionic villus sampling (CVS) and amniocentesis (AC) and the items of an assessment tool to evaluate CVS and AC competence. Methods: We used a 3-round iterative Delphi process. A steering committee supervised all processes. Seven international collaborators were identified to expand the breadth of the study internationally. The collaborators invited fetal medicine experts to participate as panelists. In the first round, the panelists suggested content for a CVS/AC curriculum and an assessment tool. The steering committee organized and condensed the suggested items and presented them to the panelists in round 2. In the second round, the panelists rated and commented on the suggested items. The results were processed by the steering committee and presented to the panelists in the third round, where final consensus was obtained. Consensus was defined as support by more than 80% of the panelists for an item. Results: Eighty-six experts agreed to participate in the study. The panelists represented 16 countries across 4 continents. The final list of curricular content included 12 theoretical and practical items. The final assessment tool included 11 items, systematically divided into 5 categories: pre-procedure, procedure, post-procedure, nontechnical skills, and overall performance. These items were provided with behavioral scale anchors to rate performance, and an entrustment scale was used for the final overall assessment. Conclusion: We established consensus among international fetal medicine experts on content to be included in a CVS/AC curriculum and on an assessment tool to evaluate CVS/AC skills. These results are important to help transition current training and assessment methods from a time- and volume-based approach to a competency-based approach which is a key step in improving patient safety and outcomes for the 2 most common invasive procedures in fetal medicine.

BACKGROUND: Systemic relapses remain a major problem in locally advanced rectal cancer. Using short-course radiotherapy followed by chemotherapy and delayed surgery, the Rectal cancer And Preoperative Induction therapy followed by Dedicated Operation (RAPIDO) trial aimed to reduce distant metastases without compromising locoregional control. METHODS: In this multicentre, open-label, randomised, controlled, phase 3 trial, participants were recruited from 54 centres in the Netherlands, Sweden, Spain, Slovenia, Denmark, Norway, and the USA. Patients were eligible if they were aged 18 years or older, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, had a biopsy-proven, newly diagnosed, primary, locally advanced rectal adenocarcinoma, which was classified as high risk on pelvic MRI (with at least one of the following criteria: clinical tumour [cT] stage cT4a or cT4b, extramural vascular invasion, clinical nodal [cN] stage cN2, involved mesorectal fascia, or enlarged lateral lymph nodes), were mentally and physically fit for chemotherapy, and could be assessed for staging within 5 weeks before randomisation. Eligible participants were randomly assigned (1:1), using a management system with a randomly varying block design (each block size randomly chosen to contain two to four allocations), stratified by centre, ECOG performance status, cT stage, and cN stage, to either the experimental or standard of care group. All investigators remained masked for the primary endpoint until a prespecified number of events was reached. Patients allocated to the experimental treatment group received short-course radiotherapy (5?*?5 Gy over a maximum of 8 days) followed by six cycles of CAPOX chemotherapy (capecitabine 1000 mg/m2 orally twice daily on days 1-14, oxaliplatin 130 mg/m2 intravenously on day 1, and a chemotherapy-free interval between days 15-21) or nine cycles of FOLFOX4 (oxaliplatin 85 mg/m2 intravenously on day 1, leucovorin [folinic acid] 200 mg/m2 intravenously on days 1 and 2, followed by bolus fluorouracil 400 mg/m2 intravenously and fluorouracil 600 mg/m2 intravenously for 22 h on days 1 and 2, and a chemotherapy-free interval between days 3-14) followed by total mesorectal excision. Choice of CAPOX or FOLFOX4 was per physician discretion or hospital policy. Patients allocated to the standard of care group received 28 daily fractions of 1·8 Gy up to 50·4 Gy or 25 fractions of 2·0 Gy up to 50·0 Gy (per physician discretion or hospital policy), with concomitant twice-daily oral capecitabine 825 mg/m2 followed by total mesorectal excision and, if stipulated by hospital policy, adjuvant chemotherapy with eight cycles of CAPOX or 12 cycles of FOLFOX4. The primary endpoint was 3-year disease-related treatment failure, defined as the first occurrence of locoregional failure, distant metastasis, new primary colorectal tumour, or treatment-related death, assessed in the intention-to-treat population. Safety was assessed by intention to treat. This study is registered with the EudraCT, 2010-023957-12, and ClinicalTrials.gov, NCT01558921, and is now complete. FINDINGS: Between June 21, 2011, and June 2, 2016, 920 patients were enrolled and randomly assigned to a treatment, of whom 912 were eligible (462 in the experimental group; 450 in the standard of care group). Median follow-up was 4·6 years (IQR 3·5-5·5). At 3 years after randomisation, the cumulative probability of disease-related treatment failure was 23·7% (95% CI 19·8-27·6) in the experimental group versus 30·4% (26·1-34·6) in the standard of care group (hazard ratio 0·75, 95% CI 0·60-0·95; p=0·019). The most common grade 3 or higher adverse event during preoperative therapy in both groups was diarrhoea (81 [18%] of 460 patients in the experimental group and 41 [9%] of 441 in the standard of care group) and neurological toxicity during adjuvant chemotherapy in the standard of care group (16 [9%] of 187 patients). Serious adverse events occurred in 177 (38%) of 460 participants in the experimental group and, in the standard of care group, in 87 (34%) of 254 patients without adjuvant chemotherapy and in 64 (34%) of 187 with adjuvant chemotherapy. Treatment-related deaths occurred in four participants in the experimental group (one cardiac arrest, one pulmonary embolism, two infectious complications) and in four participants in the standard of care group (one pulmonary embolism, one neutropenic sepsis, one aspiration, one suicide due to severe depression). INTERPRETATION: The observed decreased probability of disease-related treatment failure in the experimental group is probably indicative of the increased efficacy of preoperative chemotherapy as opposed to adjuvant chemotherapy in this setting. Therefore, the experimental treatment can be considered as a new standard of care in high-risk locally advanced rectal cancer. FUNDING: Dutch Cancer Foundation, Swedish Cancer Society, Spanish Ministry of Economy and Competitiveness, and Spanish Clinical Research Network.

Objectives Pregnancy in SSc is burdened with an increased risk of obstetric complications. Little is known about the underlying placental alterations. This study aimed to better understand pathological changes and the role of inflammation in SSc placentas. Leucocyte infiltration, inflammatory mediators and atypical chemokine receptor 2 (ACKR2) expression in SSc placentas were compared with those in other rheumatic diseases (ORD) and healthy controls (HC). Methods A case–control study was conducted on eight pregnant SSc patients compared with 16 patients with ORD and 16 HC matched for gestational age. Clinical data were collected. Placentas were obtained for histopathological analysis and immunohistochemistry (CD3, CD20, CD11c, CD68, ACKR2). Samples from four SSc, eight ORD and eight HC were analysed by qPCR for ACKR2 expression and by multiplex assay for cytokines, chemokines and growth factors involved in angiogenesis and inflammation. Results The number of placental CD3, CD68 and CD11 cells was significantly higher in patients affected by rheumatic diseases (SSc+ORD) compared with HC. Hepatocyte growth factor was significantly increased in the group of rheumatic diseases patients (SSc+ORD) compared with HC, while chemokine (C-C motif) ligand 5 (CCL5) was significantly higher in SSc patients compared with ORD and HC. CCL5 levels directly correlated with the number of all local inflammatory cells and higher levels were associated with histological villitis. Conclusions Inflammatory alterations characterize placentas from rheumatic disease patients and could predispose to obstetric complications in these subjects.

PurposeThe rollout of individualised disability funding in Australia resulted in an increased demand for services for people with a disability, particularly support for the high percentage of Australians with autism spectrum disorder. Continuing professional development is one way to grow and maintain a skilled workforce; however, face-to-face opportunities can be limited in remote areas of Australia. Technology may provide a low-cost and widely accessible platform for providing education and support for staff in these areas.Design/methodology/approachThe current study evaluated a novel webinar training and individual online support program for 36 allied health, education and community support staff. Data were collected via a survey on changes in perceived “knowledge and skills” and “confidence” in supporting children with autism, as well as mode of participation, and accessibility of the program.FindingsParticipants reported a significant increase in their “knowledge and skills” and “confidence”, in working with children with autism. This increase was positively related to the number of webinars the participants accessed. The mode of webinar access was predominantly via watching recordings of webinars (asynchronous learning). Synchronous learning via individual online sessions was accessed by a small number of participants, mostly allied health professionals. Workload and scheduling were identified as barriers to engaging in the program. The technology platform was found to be accessible and acceptable.Originality/valueA predominantly asynchronous mode of delivery was successful, thereby increasing program access and flexibility for remote staff. Technology was not a barrier to accessing the program regardless of remoteness or job role.

Anal cancer is a rare disease, albeit with an increasing incidence [1,2]. Standard treatment consists of radiotherapy with concurrent chemotherapy. The treatment outcome is affected by a number of ...

The overall aim of the thesis was to enhance and revive the practical understanding of the active ingredients in Transactional Analysis Psychotherapy (TA) and to define and lay down elements of TA that make it a distinct and replicable method of treatment. The thesis includes three empirical studies of a videotaped one-year long TA Group Therapy with 10 clients. Three different key areas of Transactional Analysis have been investigated with support of three different approaches. The first study (Johnsson, 2011 a) was a diagnostic client assessment with TA Script Analysis made as a reliability study. The second study (Johnsson, 2011 b) dealt with identification of different components in TA psychotherapy method with the use of Discourse Analysis and the third study (Johnsson & Stenlund, 2010) investigated the Therapeutic Alliance with a psychodynamic approach, using the CCRT method (the CORE Conflictual Relationship method) by Luborsky & Crits-Christoph (1990, 1998) and the Plan – Diagnosis method by Weiss & Sampson (1986). Study I: A script questionnaire and associated checklist developed by Ohlsson, Johnsson & Björk (1992) was used by the author and two professional colleagues to independently assess ten clients of a year-long transactional analysis therapy group conducted by the author. Ratings based on written responses at start of therapy were compared to ratings based on videotape interviews conducted by the author six years after termination of therapy. Moderately high inter-assessor reliability was found but intra-assessor reliability was low for the independent assessors; agreement increased for script components ‘primary injunction from father,’ ‘racket feeling’, ‘escape hatch’, ‘driver from father’ and ‘driver from mother’. Study II: Operational definitions of categorisations by McNeel (1975) were developed and applied by the author and an independent assessor to complete discourse analysis of 72 hours of transactional analysis group therapy in the style of Goulding & Goulding (1976, 1979) conducted during 1984/85. Results showed that the therapist used an average of 42% of the discourse space and that the therapy did indeed contain TA components, with the two main categories being ‘Feeling Contact’ and ‘Contracts’, and with particular use of TA techniques of ‘talking to Parent projections’, ‘make feeling statement’, ‘mutual negotiation’ and ‘specificity/clarity’. Inter-rater reliability was 46.2% (Araujo & Born 1985), Cohen’s (1960) kappa coefficient shows a spread from slight to moderate agreement, and the Odds Ratio (Viera, 2008) is above 1.0 for most categories. One intervention, "mutual negotiation", with moderate reliability could be identified as “TA typical". Study III: The study describes an investigation of the significance of the affective dimension of the therapeutic alliance (Bordin 1979), in a psychodynamic form of transactional analysis therapy after the style of “Redecision therapy” (Goulding & Goulding, 1979). We explored the client’s pattern of affective relationships by use of CCRT by Luborsky & Crits-Christoph (1990, 1998) and examined how the therapist responds to the client’s affective messages (“tests”) by use of the Plan-Diagnosis method (Weiss & Sampson, 1986). We found that “emotional” aspects play a more decisive role than has been envisioned in the TA redecision method and similar approaches of TA psychotherapy that emphasise contracts, tasks of therapy and a rational approach.

Training and support will be vital in developing and maintaining a skilled disability workforce in the roll-out of individualised disability funding across Australia. Technology has the potential t...

Background Digital tomosynthesis (DTS) might be a low-dose/low-cost alternative to computed tomography (CT). Purpose To investigate DTS relative to CT for surveillance of incidental, solid pulmonary nodules. Material and Methods Recruited from a population study, 106 participants with indeterminate solid pulmonary nodules on CT underwent surveillance with concurrently performed CT and DTS. Nodule size on DTS was assessed by manual diameter measurements and semi-automatic nodule segmentations were independently performed on CT. Measurement agreement was analyzed according to Bland–Altman with 95% limits of agreement (LoA). Detection of nodule volume change > 25% by DTS in comparison to CT was evaluated with receiver operating characteristics (ROC). Results A total of 81 nodules (76%) were assessed as measurable on DTS by two independent observers. Inter- and intra-observer LoA regarding change in average diameter were ± 2 mm. Calculation of relative volume change on DTS resulted in wide inter- and intra-observer LoA in the order of ± 100% and ± 50%. Comparing relative volume change between DTS and CT resulted in LoA of –58% to 67%. The area under the ROC curve regarding the ability of DTS to detect volumetric changes > 25% on CT was 0.58 (95% confidence interval [CI] = 0.40–0.76) and 0.50 (95% CI = 0.35–0.66) for the two observers. Conclusion The results of the present study show that measurement variability limits the agreement between DTS and CT regarding nodule size change for small solid nodules.

Background and objectives: The most efficient long-term treatment strategy for achalasia has yet to be established. This study compared the long-term results (≥ 10 years) after either pneumatic dilatations or laparoscopic myotomy using treatment failure as the primary outcome. Secondary objectives were; the frequency and degree of dysphagia and effects on health-related quality of life (QoL). Patients and methods: Out of the 53 patients with achalasia who were initially randomized to either laparoscopic myotomy with a posterior partial fundoplication (LM) or repetitive pneumatic dilatation (PD), 43 remained for scrutiny after a median observation period of 170 months (LM; n = 20 and PD; n = 23). Results: At the follow-up of 60 months, 10 patients (36%) in the PD group and two patients (8%) in the LM group were classified as treatment failures (p = 0.016). At the latest follow-up time point (≥ 10 years), the corresponding numbers were 13 (57%) and 4 (20%), respectively. The Kaplan–Meier analysis of the cumulative incidence of treatment failure revealed a significant advantage of LM over the dilatation strategy (p = 0.036)). QoL assessed by the generic instrument PGWB and the more disease-specific instrument GSRS revealed scores which were similar in the two study groups with no obvious changes over time. Reflux was better controlled in the LM group (p = 0.02 regarding PPI consumption). Conclusions: After more than a decade of follow-up, laparoscopic myotomy reinforces its superiority over repetitive pneumatic dilatation treatment strategy in the management of newly diagnosed achalasia.

Aims To evaluate the efficacy and safety of dapagliflozin (DAPA) + saxagliptin (SAXA) compared with glimepiride (GLIM) in patients with type 2 diabetes who were inadequately controlled [glycated haemoglobin (HbA1c) 7.5–10.5% (58–91 mmol/mol)] on metformin monotherapy. Materials and methods This 52‐week, multicentre, double‐blind, active‐controlled study (NCT02419612) randomized (1:1) patients on metformin to add‐on DAPA 10 mg + SAXA 5 mg (n = 227) or GLIM 1–6 mg (titrated; n = 217). The primary efficacy endpoint was change in HbA1c from baseline to week 52. Results Baseline mean ± standard deviation of age, duration of diabetes and HbA1c were 56.1 ± 9.7 years, 7.8 ± 6.4 years and 8.5% ± 0.8% (69 ± 9.0 mmol/mol), respectively. Adjusted mean change from baseline in HbA1c was −1.35% (−14.8 mmol/mol) with DAPA + SAXA versus −0.98% (−10.7 mmol/mol) with GLIM (P

Aim To assess the effects of dapagliflozin plus saxagliptin plus metformin versus glimepiride plus metformin on liver fat (proton density fat fraction) and visceral and subcutaneous adipose tissue volumes over 52 weeks of treatment. Materials and methods This was a magnetic resonance imaging substudy of a 52‐week, multicentre, randomized, double‐blind, parallel‐group trial that evaluated the efficacy and safety of dapagliflozin 10 mg/day plus saxagliptin 5 mg/day versus titrated glimepiride 1–6 mg (1, 2, 3, 4 or 6 mg) in 82 patients with type 2 diabetes (HbA1c 7.5%–10.5%) on metformin ≥1500 mg/day background. Analyses were exploratory and not controlled for multiplicity; P‐values are nominal. Results Magnetic resonance imaging was performed on 59 patients; liver fat and adipose tissue volumes were analysed for 59 and 57 patients, respectively. There was a significant >30% reduction from baseline in liver fat (P = 0.007) and >10% reduction in adipose tissue volumes (P

Aim: Efficacy and safety of dapagliflozin plus saxagliptin (DAPA + SAXA) were compared with insulin glargine (INS) in patients with type 2 diabetes (T2D) in a 52-week extension study. Materials and methods: This international Phase 3 study randomized adults with T2D on metformin with/without sulphonylurea. They received DAPA + SAXA or INS for 24 weeks (short-term) with a 28-week (long-term) extension. Week 52 exploratory endpoints included adjusted mean change from baseline in glycated haemoglobin A1c (HbA1c) and body weight, and a proportion of patients achieving optimal glycaemic response without hypoglycaemia and without requiring rescue medication. Results: Of the 1163 patients enrolled, 643 received treatment; 600 (DAPA + SAXA, 306; INS, 294) entered the long-term phase. At 52 weeks, HbA1c [adjusted least squares (LS) mean; 95% confidence interval (CI)] decreased more with DAPA + SAXA (−1.5% [−1.6%, −1.4%]) than with INS (−1.3% [−1.4%, −1.1%]); the LS mean difference (95% CI) was −0.25% (−0.4%, −0.1%; P = 0.009). Total body weight reduced with DAPA + SAXA [LS mean (95% CI): −1.8 kg (−2.4, −1.3)] and increased with INS [LS mean (95% CI): +2.8 kg (2.2, 3.3)]. More patients on DAPA + SAXA (17.6%) achieved HbA1c

Introduction Targeted temperature management (TTM) after out-of-hospital cardiac arrest (OHCA) has been recommended in international guidelines since 2005. The TTM-trial published in 2013 showed no difference in survival or neurological outcome for patients randomised to 33 °C or 36 °C, and many hospitals have changed practice. The optimal utilization of TTM is still debated. This study aimed to analyse if a difference in temperature goal was associated with outcome in an unselected international registry population. Methods This is a retrospective observational study based on a prospective registry — the International Cardiac Arrest Registry 2. Patients were categorized as receiving TTM in the lower range at 32–34 °C (TTM-low) or at 35–37 °C (TTM-high). Primary outcome was good functional status defined as cerebral performance category (CPC) of 1–2 at hospital discharge and secondary outcome was adverse events related to TTM. A logistic regression model was created to evaluate the independent effect of temperature by correcting for clinical and demographic factors associated with outcome. Results Of 1710 patients included, 1242 (72,6%) received TTM-low and 468 (27,4%) TTM-high. In patients receiving TTM-low, 31.3% survived with good outcome compared to 28.8% in the TTM-high group. There was no significant association between temperature and outcome (p = 0.352). In analyses adjusted for baseline differences the OR for a good outcome with TTM-low was 1.27, 95% CI (0.94–1.73). Haemodynamic instability leading to discontinuation of TTM was more common in TTM-low. Conclusions No significant difference in functional outcome at hospital discharge was found in patients receiving lower- versus higher targeted temperature management.

Anal cancer is a relatively rare, mostly HPV-related cancer. The curative treatment consists of concurrent chemoradiation delivered with modern radiotherapy techniques. The prognosis for most patients with early localized disease is very favourable; however patients with locally advanced disease and/or HPV negative tumours are at higher risk of locoregional and distant treatment failure. Tailored approaches are presently being investigated to determine the most suitable regimen in terms of radiotherapy dose prescription, target volume selection, normal tissue avoidance, and combination therapy. Metastatic anal cancer is treated with chemotherapy aiming at prolonged survival. The role of immune therapy in the clinical setting is being investigated. There is little knowledge on the biology of anal cancer, and an urgent need for more clinical and translational research dedicated to this disease. In this article, the evidence-base for the current treatment is briefly reviewed, and perspectives on future research needs are high-lighted.

Background Social interactions between registered nurses, older patients and their relatives are essential and play a central role in developing a successful care relationship in healthcare encounters. How nurses interact with patients affects the patient’s well-being. Limited time and demands for efficiency influence the encounter and complaints from patients and relatives often concern social interactions. Therefore, the aim of this study was to explore the social interaction in encounters between registered nurses, older patients and their relatives at a department of medicine for older people. Methods The study has an ethnographic approach including participatory observations (n = 21) and informal field conversations (n = 63), followed by a thematic analysis with an abductive approach reflecting Goffman’s interactional perspective. Result The result revealed a pattern where the participants manoeuvred between interplay and context. By manoeuvring, they defined roles but also created a common social situation. Nurses led the conversation; patients followed and described their health problems, while relatives captured the moment to receive and provide information. Finally, nurses summarised the encounter using ritual language, patients expressed gratitude through verbal and non-verbal expressions, while relatives verbally confirmed the agreements. Conclusion The social interaction between registered nurses, older patients and relatives was shaped by a pattern where the participants manoeuvred between interplay and context. When all participants assume responsibility for the social interaction, they become active and listen to each other. The approach adopted by nurses is crucial, thus training in communication and social interaction skills are important. When the asymmetry due to imbalance, is reduced, less misunderstanding and a satisfactory care relationship can be achieved.

Prior to COVID-19, research into teletherapy models for individuals on the autism spectrum was slowly progressing. Following the onset of COVID-19, teletherapy became a necessity for continuity of services, however, research was still emerging for how to translate best practice autism support to the online environment. The aim of this research was to gain insight into the rapid shift to teletherapy for practitioner and service users and the implications for the broader disability sector. Survey responses were collected from 141 allied health practitioners (speech pathologists, occupational therapists, psychologists, educators, and social workers) from four Australian states and territories. A total of 806 responses were collected from service users following an individual teletherapy session. Five themes were identified during the qualitative analysis, (1) technology—love it or hate it, (2) teletherapy as a “new normal”, (3) short term pain, for long term gain, (4) the shape of service delivery has changed, (5) is teletherapy always an option? Data from the quantitative analysis provided further insights into the first two themes. While COVID-19 has brought forward significant advances in telehealth models of practice, what is needed now is to delve further into what works, for who, and in which context, and explore the potentiality, efficiencies, and scalability of a post-pandemic hybrid approach. This will inform practice guidelines and training, as well as information for service users on what to expect.

Objective: Artificial intelligence (AI) offers new opportunities for objective quantitative measurements of imaging biomarkers from positron-emission tomography/computed tomography (PET/CT). Clinical image reporting relies predominantly on observer-dependent visual assessment and easily accessible measures like SUV max, representing lesion uptake in a relatively small amount of tissue. Our hypothesis is that measurements of total volume and lesion uptake of the entire tumour would better reflect the disease`s activity with prognostic significance, compared with conventional measurements. Methods: An AI-based algorithm was trained to automatically measure the prostate and its tumour content in PET/CT of 145 patients. The algorithm was then tested retrospectively on 285 high-risk patients, who were examined using 18F-choline PET/CT for primary staging between April 2008 and July 2015. Prostate tumour volume, tumour fraction of the prostate gland, lesion uptake of the entire tumour, and SUV max were obtained automatically. Associations between these measurements, age, PSA, Gleason score and prostate cancer-specific survival were studied, using a Cox proportional-hazards regression model. Results: Twenty-three patients died of prostate cancer during follow-up (median survival 3.8 years). Total tumour volume of the prostate (p = 0.008), tumour fraction of the gland (p = 0.005), total lesion uptake of the prostate (p = 0.02), and age (p = 0.01) were significantly associated with disease-specific survival, whereas SUV max (p = 0.2), PSA (p = 0.2), and Gleason score (p = 0.8) were not. Conclusion: AI-based assessments of total tumour volume and lesion uptake were significantly associated with disease-specific survival in this patient cohort, whereas SUV max and Gleason scores were not. The AI-based approach appears well-suited for clinically relevant patient stratification and monitoring of individual therapy.

Study Objectives We explore non-rapid eye movement (NREM) and rapid eye movement (REM) sleep homeostasis in Australian magpies (Cracticus tibicen tyrannica). We predicted that magpies would recover lost sleep by spending more time in NREM and REM sleep, and by engaging in more intense NREM sleep as indicated by increased slow-wave activity (SWA). Methods Continuous 72-h recordings of EEG, EMG, and tri-axial accelerometry, along with EEG spectral analyses, were performed on wild-caught Australian magpies housed in indoor aviaries. Australian magpies were subjected to two protocols of night-time sleep deprivation: full 12-h night (n = 8) and first 6-h half of the night (n = 5), which were preceded by a 36-h baseline recording and followed by a 24-h recovery period. Results Australian magpies recovered from lost NREM sleep by sleeping more, with increased NREM sleep consolidation, and increased SWA during recovery sleep. Following 12-h of night-time sleep loss, magpies also showed reduced SWA the following night after napping more during the recovery day. Surprisingly, the magpies did not recover any lost REM sleep. Conclusions Only NREM sleep is homeostatically regulated in Australian magpies with the level of SWA reflecting prior sleep/wake history. The significance of emerging patterns on the apparent absence of REM sleep homeostasis, now observed in multiple species, remains unclear.