The underestimated fraction: diversity, challenges and novel insights into unicellular cyanobionts of lichens.

Lichens are remarkable and classic examples of symbiotic organisms that have fascinated scientists for centuries. Yet, it has only been for a couple of decades that significant advances have focused on the diversity of their green algal and/or cyanobacterial photobionts. Cyanolichens, which contain cyanobacteria as their photosynthetic partner, include up to 10% of all known lichens and, as such, studies on their cyanobionts are much rarer compared to their green algal counterparts. For the unicellular cyanobionts, i.e. cyanobacteria that do not form filaments, these studies are even scarcer. Nonetheless, these currently include at least 10 different genera in the cosmopolitan lichen order Lichinales. An international consortium (International Network of CyanoBionts; INCb) will tackle this lack of knowledge. In this article, we discuss the status of current unicellular cyanobiont research, compare the taxonomic resolution of photobionts from cyanolichens with those of green algal lichens (chlorolichens), and give a roadmap of research on how to recondition the underestimated fraction of symbiotic unicellular cyanobacteria in lichens.

Radar for Europa Assessment and Sounding: Ocean to Near-Surface (REASON).

The Radar for Europa Assessment and Sounding: Ocean to Near-surface (REASON) is a dual-frequency ice-penetrating radar (9 and 60 MHz) onboard the Europa Clipper mission. REASON is designed to probe Europa from exosphere to subsurface ocean, contributing the third dimension to observations of this enigmatic world. The hypotheses REASON will test are that (1) the ice shell of Europa hosts liquid water, (2) the ice shell overlies an ocean and is subject to tidal flexing, and (3) the exosphere, near-surface, ice shell, and ocean participate in material exchange essential to the habitability of this moon. REASON will investigate processes governing this material exchange by characterizing the distribution of putative non-ice material (e.g., brines, salts) in the subsurface, searching for an ice-ocean interface, characterizing the ice shell's global structure, and constraining the amplitude of Europa's radial tidal deformations. REASON will accomplish these science objectives using a combination of radar measurement techniques including altimetry, reflectometry, sounding, interferometry, plasma characterization, and ranging. Building on a rich heritage from Earth, the moon, and Mars, REASON will be the first ice-penetrating radar to explore the outer solar system. Because these radars are untested for the icy worlds in the outer solar system, a novel approach to measurement quality assessment was developed to represent uncertainties in key properties of Europa that affect REASON performance and ensure robustness across a range of plausible parameters suggested for the icy moon. REASON will shed light on a never-before-seen dimension of Europa and - in concert with other instruments on Europa Clipper - help to investigate whether Europa is a habitable world.

Tissue perfusion in DIEP flaps using Indocyanine Green Fluorescence Angiography, Hyperspectral imaging, and Thermal imaging.

Flap necrosis continues to occur in skin free flap autologous breast reconstruction. Therefore, we investigated the benefits of indocyanine green angiography (ICGA) using quantitative parameters for the objective, perioperative evaluation of flap perfusion. In addition, we investigated the feasibility of hyperspectral (HSI) and thermal imaging (TI) for postoperative flap monitoring. A single-center, prospective observational study was performed on 15 patients who underwent deep inferior epigastric perforator (DIEP) flap breast reconstruction (n=21). DIEP-flap perfusion was evaluated using ICGA, HSI, and TI using a standardized imaging protocol. The ICGA perfusion curves and derived parameters, HSI extracted oxyhemoglobin (oxyHb) and deoxyhemoglobin (deoxyHb) values, and flap temperatures from TI were analyzed and correlated to the clinical outcomes. Post-hoc quantitative analysis of intraoperatively collected data of ICGA application accurately distinguished between adequately and insufficiently perfused DIEP flaps. ICG perfusion curves identified the lack of arterial inflow (n=2) and occlusion of the venous outflow (n=1). In addition, a postoperatively detected partial flap epidermolysis could have been predicted based on intraoperative quantitative ICGA data. During postoperative monitoring, HSI was used to identify impaired perfusion areas within the DIEP flap based on deoxyHb levels. The results of this study showed a limited added value of TI. Quantitative, post-hoc analysis of ICGA data produced objective and reproducible parameters that enabled the intraoperative detection of arterial and venous congested DIEP flaps. HSI appeared to be a promising technique for postoperative flap perfusion assessment. A diagnostic accuracy study is needed to investigate ICGA and HSI parameters in real-time and demonstrate their clinical benefit.

Updating Prospective Self-Efficacy Beliefs About Cardiac Interoception in Anorexia Nervosa: An Experimental and Computational Study.

Patients with anorexia nervosa (AN) typically hold altered beliefs about their body that they struggle to update, including global, prospective beliefs about their ability to know and regulate their body and particularly their interoceptive states. While clinical questionnaire studies have provided ample evidence on the role of such beliefs in the onset, maintenance, and treatment of AN, psychophysical studies have typically focused on perceptual and 'local' beliefs. Across two experiments, we examined how women at the acute AN (N = 86) and post-acute AN state (N = 87), compared to matched healthy controls (N = 180) formed and updated their self-efficacy beliefs retrospectively (Experiment 1) and prospectively (Experiment 2) about their heartbeat counting abilities in an adapted heartbeat counting task. As preregistered, while AN patients did not differ from controls in interoceptive accuracy per se, they hold and maintain 'pessimistic' interoceptive, metacognitive self-efficacy beliefs after performance. Modelling using a simplified computational Bayesian learning framework showed that neither local evidence from performance, nor retrospective beliefs following that performance (that themselves were suboptimally updated) seem to be sufficient to counter and update pessimistic, self-efficacy beliefs in AN. AN patients showed lower learning rates than controls, revealing a tendency to base their posterior beliefs more on prior beliefs rather than prediction errors in both retrospective and prospective belief updating. Further explorations showed that while these differences in both explicit beliefs, and the latent mechanisms of belief updating, were not explained by general cognitive flexibility differences, they were explained by negative mood comorbidity, even after the acute stage of illness.

Live imaging of excitable axonal microdomains in ankyrin-G-GFP mice.

The axon initial segment (AIS) constitutes not only the site of action potential initiation, but also a hub for activity-dependent modulation of output generation. Recent studies shedding light on AIS function used predominantly post-hoc approaches since no robust murine in vivo live reporters exist. Here, we introduce a reporter line in which the AIS is intrinsically labeled by an ankyrin-G-GFP fusion protein activated by Cre recombinase, tagging the native Ank3 gene. Using confocal, superresolution, and two-photon microscopy as well as whole-cell patch-clamp recordings in vitro, ex vivo, and in vivo, we confirm that the subcellular scaffold of the AIS and electrophysiological parameters of labeled cells remain unchanged. We further uncover rapid AIS remodeling following increased network activity in this model system, as well as highly reproducible in vivo labeling of AIS over weeks. This novel reporter line allows longitudinal studies of AIS modulation and plasticity in vivo in real-time and thus provides a unique approach to study subcellular plasticity in a broad range of applications.

Standardized reporting for Head CT Scans in patients suspected of traumatic brain injury (TBI): An international expert endeavor.

BACKGROUND AND PURPOSE: Traumatic brain injury (TBI) is a major source of health loss and disability worldwide. Accurate and timely diagnosis of TBI is critical for appropriate treatment and management of the condition. Neuroimaging plays a crucial role in the diagnosis and characterization of TBI. Computed tomography (CT) is the first-line diagnostic imaging modality typically utilized in patients with suspected acute mild, moderate and severe TBI. Radiology reports play a crucial role in the diagnostic process, providing critical information about the location and extent of brain injury, as well as factors that could prevent secondary injury. However, the complexity and variability of radiology reports can make it challenging for healthcare providers to extract the necessary information for diagnosis and treatment planning. METHODS/RESULTS/CONCLUSION: In this article, we report the efforts of an international group of TBI imaging experts to develop a clinical radiology report template for CT scans obtained in patients suspected of TBI and consisting of fourteen different subdivisions (CT technique, mechanism of injury or clinical history, presence of scalp injuries, fractures, potential vascular injuries, potential injuries involving the extra-axial spaces, brain parenchymal injuries, potential injuries involving the cerebrospinal fluid spaces and the ventricular system, mass effect, secondary injuries, prior or coexisting pathology).

Virtual Reality for Preoperative Surgical Planning in Complex Pediatric Oncology.

Background: Virtual reality modeling (VRM) is a 3-dimensional simulation created from patient-specific 2-dimensional (2D) imaging. VRM creates a more accurate representation of the patient anatomy and can improve anatomical perception. We surveyed surgeons on their operative plan in complex pediatric oncology cases based on review of 2D imaging and subsequently after review of VRM. We hypothesized that the confidence level would increase with the use of virtual reality and that VRM may change the operative plan. Methods: Patients were selected and enrolled based on age (<18) and oncological diagnosis. VRM was created based on the 2D imaging. Surgeons identified surgical plans based on 2D imaging and again after VRM. A blinded surgeon not involved with the case also gave opinions on surgical plans after viewing both the 2D and the VRM imaging. These assessments were compared with the actual operation. Results: A total of 12 patients were enrolled. Diagnoses included six neuroblastomas, two Wilms tumors, one Ewing's sarcoma, one pseudopapillary tumor of the pancreas, one rhabdomyosarcoma, and one mediastinal germ cell tumor. VRM increased the operating surgeon's confidence 63% of the time. The operative plan changed 8.3% of the time after VRM. Conclusion: VRM is useful to help clarify operative plans for more complex pediatric cases.

Society of Critical Care Medicine and American Society of Health-System Pharmacists Guideline for the Prevention of Stress-Related Gastrointestinal Bleeding in Critically Ill Adults.

RATIONALE: Critically ill adults can develop stress-related mucosal damage from gastrointestinal hypoperfusion and reperfusion injury, predisposing them to clinically important stress-related upper gastrointestinal bleeding (UGIB). OBJECTIVES: The objective of this guideline was to develop evidence-based recommendations for the prevention of UGIB in adults in the ICU. DESIGN: A multiprofessional panel of 18 international experts from dietetics, critical care medicine, nursing, and pharmacy, and two methodologists developed evidence-based recommendations in alignment with the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Conflict-of-interest policies were strictly followed during all phases of guideline development including task force selection and voting. METHODS: The panel members identified and formulated 13 Population, Intervention, Comparison, and Outcome questions. We conducted a systematic review for each question to identify the best available evidence, statistically analyzed the evidence, and then assessed the certainty of the evidence using the GRADE approach. We used the evidence-to-decision framework to formulate the recommendations. Good practice statements were included to provide additional guidance. RESULTS: The panel generated nine conditional recommendations and made four good practice statements. Factors that likely increase the risk for clinically important stress-related UGIB in critically ill adults include coagulopathy, shock, and chronic liver disease. There is no firm evidence for mechanical ventilation alone being a risk factor. Enteral nutrition probably reduces UGIB risk. All critically ill adults with factors that likely increase the risk for stress-related UGIB should receive either proton pump inhibitors or histamine-2 receptor antagonists, at low dosage regimens, to prevent UGIB. Prophylaxis should be discontinued when critical illness is no longer evident or the risk factor(s) is no longer present despite ongoing critical illness. Discontinuation of stress ulcer prophylaxis before transfer out of the ICU is necessary to prevent inappropriate prescribing. CONCLUSIONS: The guideline panel achieved consensus regarding the recommendations for the prevention of stress-related UGIB. These recommendations are intended for consideration along with the patient's existing clinical status.

Dissecting the components of error in analogue report tasks : Error in analogue report tasks.

Over the last two decades, the analogue report task has become a standard method for measuring the fidelity of visual representations across research domains including perception, attention, and memory. Despite its widespread use, there has been no methodical investigation of the different task parameters that might contribute to response variability. To address this gap, we conducted two experiments manipulating components of a typical analogue report test of memory for colour hue. We found that human response errors were independently affected by changes in storage and maintenance requirements of the task, demonstrated by a strong effect of set size even in the absence of a memory delay. In contrast, response variability remained unaffected by physical size of the colour wheel, implying negligible contribution of motor noise to task performance, or by its chroma radius, highlighting non-uniformity of the standard colour space. Comparing analogue report to a matched forced-choice task, we found variation in adjustment criterion made a limited contribution to analogue report variability, becoming meaningful only with low representational noise. Our findings validate the analogue report task as a robust measure of representational fidelity for most purposes, while also quantifying non-representational sources of noise that would limit its reliability in specialized settings.

Relation between the internal anal sphincter and defecation disorders in patients with anorectal malformations.

OBJECTIVES: To investigate associations between the rectoanal inhibitory reflex (RAIR), type of congenital anorectal malformations (ARMs), type of operation that patients with ARM had undergone, and objectively measured fecal incontinence and defecation problems. METHODS: We retrospectively included 69 pediatric patients with ARM. All underwent anorectal function tests at the University Medical Center of Groningen during the last 10 years. We assessed anorectal physiology using the Rome IV criteria and anorectal function tests. RESULTS: We found the reflex in 67% of patients and all types of ARMs. All patients who had not been operated on, and those who had undergone less extensive surgery possessed the reflex. In contrast, patients who underwent posterior sagittal anorectoplasty, 44% possessed it. We found no difference between mean rectal volumes in patients with and without the reflex (251 mL vs. 325 mL, respectively, p = 0.266). We found that over time, patients without the reflex seemed to develop significantly higher rectal volumes than patients who had it. We did not find a significant difference between the reflex and fecal incontinence; however, it seems that the absence of the reflex, resting anal sphincter pressure, and fecal incontinence are related. CONCLUSION: The RAIR seems present in patients with ARM irrespective of their malformation type. Corrective surgery, however, may impair this reflex. Seemingly, its absence results in constipation with enlarged rectal volumes and fecal incontinence. Every effort should be made to preserve this reflex during surgery and to use extensive surgical procedures as sparingly as possible.

Brain Cell-based Genetic Subtyping and Drug Repositioning for Alzheimer Disease.

Alzheimer's Disease (AD) is characterized by its complex and heterogeneous etiology and gradual progression, leading to high drug failure rates in late-stage clinical trials. In order to better stratify individuals at risk for AD and discern potential therapeutic targets we employed a novel procedure utilizing cell-based co-regulated gene networks and polygenic risk scores (cbPRSs). After defining genetic subtypes using extremes of cbPRS distributions, we evaluated correlations of the genetic subtypes with previously defined AD subtypes defined on the basis of domain-specific cognitive functioning and neuroimaging biomarkers. Employing a PageRank algorithm, we identified priority gene targets for the genetic subtypes. Pathway analysis of priority genes demonstrated associations with neurodegeneration and suggested candidate drugs currently utilized in diabetes, hypertension, and epilepsy for repositioning in AD. Experimental validation utilizing human induced pluripotent stem cell (hiPSC)-derived astrocytes demonstrated the modifying effects of estradiol, levetiracetam, and pioglitazone on expression of APOE and complement C4 genes, suggesting potential repositioning for AD.

Template-assisted covalent modification underlies activity of covalent molecular glues.

Molecular glues are proximity-inducing small molecules that have emerged as an attractive therapeutic approach. However, developing molecular glues remains challenging, requiring innovative mechanistic strategies to stabilize neoprotein interfaces and expedite discovery. Here we unveil a trans-labeling covalent molecular glue mechanism, termed 'template-assisted covalent modification'. We identified a new series of BRD4 molecular glue degraders that recruit CUL4DCAF16 ligase to the second bromodomain of BRD4 (BRD4BD2). Through comprehensive biochemical, structural and mutagenesis analyses, we elucidated how pre-existing structural complementarity between DCAF16 and BRD4BD2 serves as a template to optimally orient the degrader for covalent modification of DCAF16Cys58. This process stabilizes the formation of BRD4-degrader-DCAF16 ternary complex and facilitates BRD4 degradation. Supporting generalizability, we found that a subset of degraders also induces GAK-BRD4BD2 interaction through trans-labeling of GAK. Together, our work establishes 'template-assisted covalent modification' as a mechanism for covalent molecular glues, which opens a new path to proximity-driven pharmacology.

A combined radio-immunotherapy regimen eradicates late-stage tumors in mice.

Background: The majority of experimental approaches for cancer immunotherapy are tested against relatively small tumors in tumor-bearing mice, because in most cases advanced cancers are resistant to the treatments. In this study, we asked if even late-stage mouse tumors can be eradicated by a rationally designed combined radio-immunotherapy (CRI) regimen. Methods: CRI consisted of local radiotherapy, intratumoral IL-12, slow-release systemic IL-2 and anti- CTLA-4 antibody. Therapeutic effects of CRI against several weakly immunogenic and immunogenic mouse tumors including B78 melanoma, MC38 and CT26 colon carcinomas and 9464D neuroblastoma were evaluated. Immune cell depletion and flow cytometric analysis were performed to determine the mechanisms of the antitumor effects. Results: Tumors with volumes of 2,000 mm3 or larger were eradicated by CRI. Flow analyses of the tumors revealed reduction of T regulatory (Treg) cells and increase of CD8/Treg ratios following CRI. Rapid shrinkage of the treated tumors did not require T cells, whereas T cells were involved in the systemic effect against the distant tumors. Cured mice developed immunological memory. Conclusions: These findings underscore that rationally designed combination immunotherapy regimens can be effective even against large, late-stage tumors.

Interleukin-6 and Cardiovascular Events in Healthy Adults: MESA.

Background: Elevated interleukin (IL)-6 levels have been linked to adverse outcomes in patients with and without baseline cardiovascular disease (CVD). Objectives: The purpose of this study was to examine the association between circulating IL-6 levels and CVD events without baseline CVD across racial and ethnic groups. Methods: We conducted an observational analysis utilizing the MESA (Multi-Ethnic Study of Atherosclerosis), a multicenter, prospective community-based study of CVD at baseline from four racial and ethnic groups. IL-6 levels were measured at the time of enrollment (visit 1) and were divided into 3 terciles. Patient baseline characteristics and outcomes, including all-cause mortality, CV mortality, heart failure, and non-CV mortality, were included. Cox proportional hazard regression models were used to assess associations between IL-6 levels and study outcomes with IL-6 tercile 1 as reference. Results: Of 6,622 individuals, over half were women (53%) with a median age of 62 (IQR: 53-70) years. Racial and ethnic composition was non-Hispanic White (39%) followed by African American (27%), Hispanic (22%), and Chinese American (12%). Compared to tercile 1, participants with IL-6 tercile 3 had a higher adjusted risk of and all-cause mortality (HR: 1.98 [95% CI: 1.67-2.36]), CV mortality (HR: 1.55 [95% CI: 1.05-2.30]), non-CV mortality (HR: 2.05 [95% CI: 1.65-2.56]), and heart failure (HR: 1.48 [95% CI: 0.99-2.19]). When tested as a continuous variable, higher levels of IL-6 were associated with an increased risk of all individual outcomes. Compared to non-Hispanic White participants, the unadjusted and adjusted risk of all outcomes across all races and ethnicities was similar across all IL-6 terciles. Conclusions: High levels of circulating IL-6 are associated with worse CV outcomes and increased all-cause mortality consistently across all racial and ethnic groups.

A randomized clinical trial comparing the effects of music and informative videos on patient anxiety during root canal treatment and retreatment.

OBJECTIVES: This randomized clinical trial compared the effectiveness of music and informative videos as distraction tools to reduce the anxiety of patients during root canal treatment and retreatment. METHOD AND MATERIALS: A total of 90 patients were enrolled in the study. The patients were randomly allocated to three groups: Group 1 listened to music during the treatment (n=30), Group 2 watched an informative pre-operative video (n=30) and a control group underwent treatment without a distraction method (n=30). Prior to treatment, the Corah Dental Anxiety Scale (CDAS) and a visual analogue pain scale (VAS) were used to assess anxiety and pre-operative pain. Systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR) and oxygen saturation (OS) were recorded before the intervention (T1), after the local anesthetic (T2), following pulp extirpation or removal of root fillings (T3), and immediately following rubber dam removal (T4). One-Way ANOVA, followed by post-hoc Bonferroni tests for multiple comparisons, were used to compare mean values of SBP, DBP, HR, and OS among the groups. A P-value of 5% was considered as significant. RESULTS: Listening to music reduced SBP, HR (P <.001) and DBP (P =.003) in patients undergoing root canal treatment and retreatment at T4 compared to the baseline (T1). Music (P <.001) and informative video (P =.003) groups had significantly lower post-operative VAS-pain scores. CONCLUSION: Listening to music during root canal treatment and retreatment reduced anxiety levels in patients compared to informative pre-operative videos and no distraction technique. Pre-registration: Australian New Zealand Clinical Trials Registry (ACTRN12622000817741).

Radiation Therapy for HPV-Positive Oropharyngeal Squamous Cell Carcinoma: An ASTRO Clinical Practice Guideline.

PURPOSE: Human Papilloma Virus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is a distinct disease from other head and neck tumors. This guideline provides evidence-based recommendations on the critical decisions in its curative treatment, including both definitive and postoperative radiation therapy (RT) management. METHODS: ASTRO convened a task force to address 5 key questions on the use of RT for management of HPV-associated OPSCC. These questions included indications for definitive and postoperative RT and chemoradiation; dose-fractionation regimens and treatment volumes; preferred RT techniques and normal tissue considerations; and posttreatment management decisions. The task force did not address indications for primary surgery versus RT. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength. RESULTS: Concurrent cisplatin is recommended for patients receiving definitive RT with T3-4 disease and/or 1 node >3 cm, or multiple nodes. For similar patients who are ineligible for cisplatin, concurrent cetuximab, carboplatin/5-fluorouracil, or taxane-based systemic therapy are conditionally recommended. In the postoperative setting, RT with concurrent cisplatin (either schedule) is recommended for positive surgical margins or extranodal extension. Postoperative RT alone is recommended for pT3-4 disease, >2 nodes, or a single node >3 cm. Observation is conditionally recommended for pT1-2 disease and a single node ≤3 cm without other risk factors. For patients treated with definitive RT with concurrent systemic therapy, 7000 cGy in 33 to 35 fractions is recommended, and for patients receiving postoperative RT without positive surgical margins and extranodal extension, 5600 to 6000 cGy is recommended. For all patients receiving RT, intensity modulated RT over 3-dimensional techniques with reduction in dose to critical organs at risk (including salivary and swallowing structures) is recommended. Reassessment with positron emission tomography-computed tomography is recommended approximately 3 months after definitive RT/chemoradiation, and neck dissection is recommended for convincing evidence of residual disease; for equivocal positron emission tomography-computed tomography findings, either neck dissection or repeat imaging is recommended. CONCLUSIONS: The role and practice of RT continues to evolve for HPV-associated OPSCC, and these guidelines inform best clinical practice based on the available evidence.

One- and 2-year outcomes of lumbar facet arthroplasty versus spinal fusion in young (<65 years) and old (≥65 years) patients for the treatment of degenerative spondylolisthesis and stenosis.

Background: Facet arthroplasty, an alternative to lumbar fusion, offers stabilization and preserves range of motion. This subanalysis of the TOPS IDE trial (FDA #G160168) compared facet arthroplasty, using the TOPS device, with a standard single-level transforaminal lumbar interbody fusion (TLIF) in patients stratified by age (<65 and ≥65 years) with symptomatic grade 1 degenerative spondylolisthesis with moderate to severe spinal stenosis at L2-5. Methods: Patient-reported outcomes (PROMS), including Oswestry disability index (ODI), visual analog pain scales (VAS), and Zurich claudication questionnaires (ZCQ), were assessed at baseline and multiple postoperative timepoints. Radiographic evaluation of flexion/extension range of motion (ROM) occurred at baseline, 12 months, and 24 months. Data were analyzed following an intention-to-treat model. Significance was defined as p<.05. Results: About 299 patients were included (TOPS=206, TLIF=93). The groups were similar at baseline. At 2 years, the TOPS group had a greater proportion of patients report ≥15-point improvement for ODI (93.8% versus 77.1%, p=.011) and ≥20-point improvement for VAS back (84.4% versus 61.8%, p=.014). At 1 year, TOPS group had a greater proportion of patients report clinically significant improvements in all ZCQ categories (91.6% versus 78.5%, p=.012). In patients <65 years, the TOPS group had improved PROMS compared to TLIF at 2 years; however, these differences were less pronounced in patients ≥65 years old. The TOPS groups preserved more ROM at 12 (2.8° 95%CI [1.87; 3.74], p<.0001) and 24 (2.99° 95%CI [1.82; 4.15], p<.0001) months compared to TLIF. ROM was similarly preserved in patients aged <65 and ≥65. The rate of adverse events did not differ significantly between treatment groups. Conclusions: Facet arthroplasty preserves more ROM in all ages and leads to improved PROMS compared to TLIF, particularly in younger patients.

Demonstrating the use of population level data to investigate trends in the rate, radiation dose and cost of Computed Tomography across clinical groups: Are there any areas of concern?

INTRODUCTION: Increases in computed tomography (CT) use may not always reflect clinical need or improve outcomes. This study aimed to demonstrate how population level data can be used to identify variations in care between patient groups, by analysing system-level changes in CT use around the diagnosis of new conditions. METHODS: Retrospective repeated cross-sectional observational study using West Australian linked administrative records, including 504,723 adults diagnosed with different conditions in 2006, 2012 and 2015. For 90 days pre/post diagnosis, CT use (any and 2+ scans), effective dose (mSv), lifetime attributable risk (LAR) of cancer incidence and mortality from CT, and costs were assessed. RESULTS: CT use increased from 209.4 per 1000 new diagnoses in 2006 to 258.0 in 2015; increases were observed for all conditions except neoplasms. Healthcare system costs increased for all conditions but neoplasms and mental disorders. Effective dose increased substantially for respiratory (+2.5 mSv, +23.1%, P < 0.001) and circulatory conditions (+2.1 mSv, +15.4%, P < 0.001). The LAR of cancer incidence and mortality from CT increased for endocrine (incidence +23.4%, mortality +18.0%) and respiratory disorders (+21.7%, +23.3%). Mortality LAR increased for circulatory (+12.1%) and nervous system (+11.0%) disorders. The LAR of cancer incidence and mortality reduced for musculoskeletal system disorders, despite an increase in repeated CT in this group. CONCLUSIONS: Use and costs increased for most conditions except neoplasms and mental and behavioural disorders. More strategic CT use may have occurred in musculoskeletal conditions, while use and radiation burden increased for respiratory, circulatory and nervous system conditions. Using this high-level approach we flag areas requiring deeper investigation into appropriateness and value of care.