Blinded Expert Panel Research Articles

The utility of artificial intelligence platforms for patient-generated questions in Mohs micrographic surgery: amulti-national, blinded expert panel evaluation.

Artificial intelligence (AI) and large language models (LLMs) transform how patients inform themselves. LLMs offer potential as educational tools, but their quality depends upon the information generated. Current literature examining AI as an informational tool in dermatology has been limited in evaluating AI's multifaceted roles and diversity of opinions. Here, we evaluate LLMs as a patient-educational tool for Mohs micrographic surgery (MMS) in and out of the clinic utilizing an international expert panel. The most common patient MMS questions were extracted from Google and transposed into two LLMs and Google's search engine. 15 MMS surgeons evaluated the generated responses, examining their appropriateness as a patient-facing informational platform, sufficiency of response in a clinical environment, and accuracy of content generated. Validated scales were employed to assess the comprehensibility of each response. The majority of reviewers deemed all LLM responses appropriate. 75% of responses were rated as mostly accurate or higher. ChatGPT had the highest mean accuracy. The majority of the panel deemed 33% of responses sufficient for clinical practice. The mean comprehensibility scores for all platforms indicated a required 10th-grade reading level. LLM-generated responses were rated as appropriate patient informational sources and mostly accurate in their content. However, these platforms may not provide sufficient information to function in a clinical environment, and complex comprehensibility may represent a barrier to utilization. As the popularity of these platforms increases, it is important for dermatologists to be aware of these limitations.

Diagnostic accuracy of a smartphone application for artificial intelligence-based interpretation of 12-lead ECG in primary care (AMSTELHEART-1)

Abstract Background The use of 12-lead electrocardiogram (ECG) is common in routine primary care, however it can be difficult for less experienced ECG readers to adequately interpret the ECG. Objective To validate a novel smartphone application as a stand-alone interpretation tool for 12-lead ECG in primary care. Methods We recruited consecutive patients who underwent 12-lead ECG as part of routinely indicated primary care in the Netherlands. All ECGs were assessed by a smartphone application which analyses a photographed image of 12-lead ECG for automated interpretation, installed on an Android platform and an iOS platform. We validated the application for detecting: 1) any major ECG abnormality (MEA, primary outcome) defined as atrial fibrillation/flutter (AF), markers of (past) myocardial ischemia or clinically relevant impulse and/or conduction abnormalities; or 2) AF (key secondary outcome). The reference standard was a blinded expert panel. Results We included 290 patients from 11 Dutch general practices with median age 67 (IQR 55-74) years, 48% were female. On reference ECG, 71 patients (25%) had MEA, 35 (12%) had AF. The app's sensitivity and specificity for MEA were 86% (95%CI:76-93) and 92% (95%CI:87-95), respectively. For AF, sensitivity and specificity were 97% (95%CI:85-100) and 99% (95%CI:97-100), respectively. Performance was comparable between Android and iOS platform (Kappa=0.95, 95%CI:0.91-0.99 and Kappa=1.00, 95%CI:1.00-1.00 for MEA and AF, respectively). Conclusions A smartphone application that interprets photographed 12-lead ECG images had good diagnostic accuracy in a primary care setting for major ECG abnormalities, and near-perfect properties for diagnosing AF.

Diagnostic accuracy of the PMcardio smartphone application for artificial intelligence–based interpretation of electrocardiograms in primary care (AMSTELHEART-1)

The use of 12-lead electrocardiogram (ECG) is common in routine primary care, however it can be difficult for less experienced ECG readers to adequately interpret the ECG. To validate a smartphone application (PMcardio) as a stand-alone interpretation tool for 12-lead ECG in primary care. We recruited consecutive patients who underwent 12-lead ECG as part of routinely indicated primary care in the Netherlands. All ECGs were assessed by the PMcardio app, which analyzes a photographed image of 12-lead ECG for automated interpretation, installed on an Android platform (Samsung Galaxy M31) and an iOS platform (iPhone SE2020). We validated the PMcardio app for detecting any major ECG abnormality (MEA, primary outcome), defined as atrial fibrillation/flutter (AF), markers of (past) myocardial ischemia, or clinically relevant impulse and/or conduction abnormalities; or AF (key secondary outcome) with a blinded expert panel as reference standard. We included 290 patients from 11 Dutch general practices with median age 67 (interquartile range 55-74) years; 48% were female. On reference ECG, 71 patients (25%) had MEA and 35 (12%) had AF. Sensitivity and specificity of PMcardio for MEA were 86% (95% CI: 76%-93%) and 92% (95% CI: 87%-95%), respectively. For AF, sensitivity and specificity were 97% (95% CI: 85%-100%) and 99% (95% CI: 97%-100%), respectively. Performance was comparable between Android and iOS platform (kappa = 0.95, 95% CI: 0.91-0.99 and kappa = 1.00, 95% CI: 1.00-1.00 for MEA and AF, respectively). A smartphone app developed to interpret 12-lead ECGs was found to have good diagnostic accuracy in a primary care setting for major ECG abnormalities, and near-perfect properties for diagnosing AF.

Evaluating the Mystery of ‘Brushy Bill’ Roberts (aka., Billy the Kid) as a Case of Extreme Celebrity Worship

‘Brushy Bill’ Roberts gained notoriety in 1950 for identifying himself as the presumably deceased outlaw ‘Billy the Kid.’ We hypothesized that his case reflected extreme celebrity worship, which involves psychological absorption with a target celebrity and potential fantasy-reality breakdowns. A blinded expert panel mapped Roberts’ claims, activities, and circumstances against the three phases of celebrity worship and their known correlates. Outcomes from this exercise suggested that: (a) his reported attitudes and behaviors equated to an above-average score on the Celebrity Worship Scale (McCutcheon, Lange, & Houran, 2002), (b) his identity as the Kid unfolded somewhat similarly to the behavioral progression of celebrity worship, and (c) he ostensibly had the most psychosocial risk factors for the ‘Entertainment-Social’ level of celebrity worship, though many were also noted for the more extreme ‘Intense-Personal’ and ‘Borderline Pathological’ phases. These results imply that Roberts might have consciously adopted Billy the Kid as an alter ego primarily for leisure and escapism, although this construction perhaps evolved to include more compulsory or addictive aspects.
 Keywords: absorption, alter ego, celebrity worship, grandiose delusions, narrative reality

Physical Therapists Are Routinely Performing the Requisite Skills to Directly Refer for Musculoskeletal Imaging: An Observational Study

ABSTRACT Objectives To explore if physical therapists are practicing skills necessary to refer patients for musculoskeletal imaging. Methods An expert panel established a list of nine requisite skills to refer for musculoskeletal imaging. A blinded expert panel validated the list using a 5-point Likert scale. The skills list was examined via an electronic survey distributed to United States physical therapists. Results 4,796 respondents were included. Each of the nine skills were routinely performed by a majority of the respondents (range: 54.52–94.72%). Respondents routinely performed 6.95 (± 0.06) skills, with 67.41% routinely performing seven or more skills. Doctors of physical therapy routinely performed more imaging skills (7.15 ± 0.06) compared to their masters- (6.44 ± 0.19) and bachelors-trained (5.95 ± 0.21) counterparts (p < 0.001). Residency/fellowship-trained physical therapists were more likely to routinely perform more imaging skills (7.60 ± 0.11 vs. 6.79 ± 0.07, p < 0.001). Imaging skill performance was greater among board-certified physical therapists (7.39 ± 0.09 vs. 6.71 ± 0.08, p < 0.001) and APTA members (7.06 ± 0.07 vs. 6.65 ± 0.12, p < 0.001). Conclusion Physical therapists are routinely practicing the requisite imaging skills to directly refer to a radiologist for musculoskeletal imaging.

The effect of Computerised Physician Order Entry on prescribing errors: An interrupted time-series study at a secondary referral hospital in Australia

BackgroundComputerised Physician Order Entry (CPOE) software is increasingly used across the world to improve medication safety. However, few high-quality studies have reviewed the impact of CPOE on prescribing errors and patient harm. ObjectiveTo investigate the effect of a hybrid CPOE-paper prescribing system on prescribing errors at a secondary hospital site. DesignAn interrupted time-series study was conducted by identifying prescribing errors via prospective medical chart review before and after the implementation of CPOE across three medical wards. ParticipantsThe medication orders of all patients admitted to the medical wards during the study period were reviewed. InterventionImplementation of a CPOE across three medical wards. MeasuresA blinded expert panel risk stratified the errors according to level of severity, preventability and potential for harm. Pearson’s chi square and segmented regressions were used to determine if there were differences in prescribing errors pre- and post-CPOE implementation. Key resultsA total of 10,535 medication orders were reviewed pre-CPOE and 13,841 medication orders reviewed post-CPOE. Analysis demonstrated that after implementation of CPOE there were reductions in the proportion of orders with one or more of any error (−30.1%, 95 %CI: −36.5%, −23.7%, p < 0.001). Reductions in the proportion of orders with one or more errors were seen across the error categories of dosing errors (-20.1%, 95 %CI: −25.1%, −15%, p < 0.001), procedural/administrative errors (-18.9%, 95 %CI: −22.8%, −15%, p < 0.001), and therapeutic errors (-2.6%, 95 %CI: −4.1%, −1%, p = 0.002). Post-CPOE there were reductions in the proportion of orders with at least one non-intercepted serious error (-12.6%, 95 %CI: −16.4%, −8.8%, p < 0.001). ConclusionThe introduction of CPOE was associated with reductions in prescribing errors. There is also evidence that this translated into a reduced risk of harm to patients post-CPOE implementation through the reduction in actual adverse drug events.

Impact of Platelet Transfusion on Pulmonary Function of Hematology Oncology Patients: The Piper Study

Background. Platelet transfusion is a critical therapy for hematology-oncology patients at risk of transfusion-transmitted infection (TTI) and pulmonary injury. Amotosalen-UVA pathogen reduction (PR) treatment of apheresis platelet components (PC) in plasma or additive solution (INTERCEPT Blood System for Platelets, Cerus, Concord, CA) is FDA approved to reduce risk of TTI and transfusion associated graft vs. host disease (TA-GVHD). PRPC meet the FDA bacteria risk reduction guidance, and approximately 50% of U.S. PC are PRPC. Amotosalen-UVA PR replaces bacteria screening, gamma irradiation, and CMV serology. PR is performed within 24 hours of collection enabling early release of PRPC with 5-day storage. We tested the hypothesis that PRPC were not inferior to conventional PC(CPC) for the incidence of pulmonary injury. Methods. An open-label sequential cohort study in platelet transfusion dependent hematology-oncology patients was conducted under routine practice conditions in 15 clinical centers. Each site enrolled a CPC cohort followed by a PRPC cohort using 4 primary therapy strata matched ± 10%: chemotherapy without hematopoietic cell transplant (HCT), HCT with myeloablation, HCT with non-myeloablative conditioning, and HCT with reduced intensity conditioning (RIC). Patients were supported with the assigned PC type for up to 21 days with 7 days of surveillance after the last PC exposure. Patients participated in only one cohort. The primary endpoint was treatment emergent assisted mechanical ventilation (TEAMV) by intubation or tight mask with positive end expiration pressure (5cm H 2O) after initiation of study PC. All endpoint patients were adjudicated by a blinded pulmonary expert panel (PEP) for diagnosis of acute respiratory distress syndrome (ARDS) by the Berlin Criteria. Secondary endpoints included: time to initiation of TEAMV, clinically significant pulmonary adverse events (CSPAE, CTCAE ≥ Grade 2), transfusion reactions, and mortality. The incidence of TEAMV by non-inferiority (margin = 2.3%), and secondary endpoints were analyzed by modified intention to treat (mITT) and per protocol (PP). Sensitivity analyses with propensity score matching for key variables were conducted for the primary endpoint. The associations between PC and categorical variables were tested by stratified Cochran-Mantel-Haenszel and continuous variables by ANOVA for two-sided significance p = 0.05. results. A total of 2291 pediatric and adult patients (1068 PRPC and 1223 CPC) were enrolled in the respective cohorts with transfusion of 5,277 PRPC and 5,491 CPC. PC assignment compliance and study completion were > 94%. For the mITT data set, the cumulative incidence of TEAMV was lower for the PRPC cohort (log rank p = 0.039) than the CPC cohort (2.9% versus 4.6%, HR = 0.633: 95% CI 0.408-0.982). PRPC by mITT were non-inferior to CPC for the incidence of TEAMV due to all indications, and for TEAMV with pulmonary dysfunction (PD) by PEP (Table). PP analyses were consistent with mITT. Relative risk (RR) of TEAMV showed significantly (p<0.05) decreased RR of PRPC respectively for baseline covariates: age < 65 (0.53), male (0.54), non-white (0.32), chemotherapy (0.40), prior pulmonary disease (0.55), and prior cardiac disease (0.58). Least squares (LS) mean days to initiation of TEAMV for patients with PD were longer for PRPC recipients. PEP adjudicated incidence of ARDS was not significantly different between cohorts (Table). Total and serious CSPAE were not different between the cohorts. There were no significant differences between cohorts in Respiratory, Thoracic, and Mediastinal Disorders, the most frequent system organ class event. Mortality was not different between cohorts. Multivariate analysis (mITT) for the probability of CSPAE or transfusion associated cardiac overload (TACO) showed PC type had no effect. The odds ratio (OR) of CSPAE or TACO during PC support was significantly increased (p< 0.05) in both cohorts for history of cardiac disease (1.35), history of pulmonary disease (2.57), diagnosis of Myelodysplasia (1.88), and diagnosis of Myelodysplasia/Myeloproliferative disease (2.27). There was a significant treatment interaction (p= 0.043) between PC type and acute myelogenous leukemia (AML), increased OR = 1.49 for CPC versus PRPC. Conclusions. PRPC did not potentiate pulmonary injury during PC support; and their use may decrease TEAMV risk with benefit of reduced TTI risk. [Display omitted] DisclosuresWheeler: Novo Nordisk A/S: Consultancy; Bayer: Consultancy; BioMarin: Consultancy; HEMA Biologics: Consultancy; Spark: Consultancy; Takeda: Consultancy; UniQure: Consultancy. Nooka: Janssen Oncology: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Sanofi: Consultancy; Oncopeptides: Consultancy; Amgen: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy; Adaptive technologies: Consultancy; GlaxoSmithKline: Consultancy, Other: Travel expenses; Karyopharm Therapeutics: Consultancy. Uhl: UpToDate: Patents & Royalties; Abbott: Consultancy, Speakers Bureau; Grifols: Consultancy, Speakers Bureau. Spinella: Secure Transfusion Services: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company; Cerus Corporation: Consultancy, Research Funding. Liu: Cerus Corporation: Current Employment, Current equity holder in publicly-traded company. Benjamin: Cerus Corporation: Current Employment, Current equity holder in publicly-traded company. Corash: Cerus Corporation: Current Employment, Current equity holder in publicly-traded company.

A retrospective evaluation of treatment decision making for thyroid cancer using clinical decision support in Brazil.

e19193 Background: Artificial intelligence-driven clinical decision-support systems such as Watson for Oncology (WfO) may aid cancer care in economically challenged health systems. Evidence of the applicability of such tools in resource-constrained settings is limited. The study objective was to evaluate treatment agreement between physician-prescribed therapy and WfO recommended treatment options in thyroid cancer in Brazil. An in-depth evaluation of discordant cases by a blinded expert panel of medical oncologists and cancer surgeons was performed to identify preferred therapies and predictors of discordance. Methods: Thyroid cancer patients treated at the Instituto do Câncer do Ceará, Brazil from July 2018 to June 2019, but not processed in WfO, were selected for entry into WfO in January 2020. Blinded to treatment-plan source (i.e., WfO or historical), the expert panel reviewed all WfO therapeutic options and historical physician-prescribed treatment plans for discordant cases and selected their preferred treatment options. Clinical and demographic characteristics were analyzed using logistic regression. Results: Thyroid cancer patients (n = 83) evaluated for concordance between WfO therapeutic options and historical treatments were mostly female (91%) and between the ages of 18 - 78 years (mean 47.7). Concordance between historical physician-prescribed treatment decisions and WfO was 73.5% (61/83). Demographics and clinical characteristics associated with discordance are shown in Table. For all discordant cases (n = 22), preferred treatment decisions, as determined by the expert panel, were in agreement with WfO. Conclusions: High concordance between WfO recommended treatment options and historical treatment decisions for thyroid cancer was observed at Instituto do Câncer do Ceará. For discordant cases, a blinded expert panel agreed with WfO recommended treatment options in all cases, demonstrating there may be a role for decision support in aiding individual oncologists to make best-practice and evidence-informed treatment decisions. [Table: see text]

HOPON (Hyperbaric Oxygen for the Prevention of Osteoradionecrosis): a randomised controlled trial of hyperbaric oxygen to prevent osteoradionecrosis of the irradiated mandible: study protocol for a randomised controlled trial

BackgroundOsteoradionecrosis of the mandible is the most common serious complication of radiotherapy for head and neck malignancy. For decades, hyperbaric oxygen has been employed in efforts to prevent those cases of osteoradionecrosis that are precipitated by dental extractions or implant placement. The evidence for using hyperbaric oxygen remains poor and current clinical practice varies greatly. We describe a protocol for a clinical trial to assess the benefit of hyperbaric oxygen in the prevention of osteoradionecrosis during surgery on the irradiated mandible.Methods/designThe HOPON trial is a phase III, randomised controlled, multi-centre trial. It employs an unblinded trial design, but the assessment of the primary endpoint, i.e. the diagnosis of osteoradionecrosis, is assessed on anonymised clinical photographs and radiographs by a blinded expert panel. Eligibility is through the need for a high-risk dental procedure in the mandible where at least 50-Gy radiotherapy has been received. Patients are randomised 1:1 to hyperbaric oxygen arm (Marx protocol) : control arm, but both groups receive antibiotics and chlorhexidine mouthwash. The primary endpoint is the presence of osteoradionecrosis at 6 months following surgery, but secondary endpoints include other time points, acute symptoms and pain, quality of life, and where implants are placed, their successful retention.DiscussionThe protocol presented has evolved through feasibility stages and through analysis of interim data. The classification of osteoradionecrosis has undergone technical refinement to ensure that robust definitions are employed. The HOPON trial is the only multi-centre RCT conducted in this clinical setting despite decades of use of hyperbaric oxygen for the prevention of osteoradionecrosis.Trial registrationEuropean Clinical Trials Database, ID: EudraCT200700622527. First registered on 5 November 2007.

Rituximab as treatment for anti-MuSK myasthenia gravis: Multicenter blinded prospective review.

To evaluate the efficacy of rituximab in treatment of anti-muscle-specific kinase (MuSK) myasthenia gravis (MG). This was a multicenter, blinded, prospective review, comparing anti-MuSK-positive patients with MG treated with rituximab to those not treated with rituximab. The primary clinical endpoint was the Myasthenia Gravis Status and Treatment Intensity (MGSTI), a novel outcome that combines the Myasthenia Gravis Foundation of America (MGFA) postintervention status (PIS) and the number and dosages of other immunosuppressant therapies used. A priori, an MGSTI of level ≤2 was used to define a favorable outcome. Secondary outcomes included modified MGFA PIS of minimal manifestations or better, mean/median prednisone dose, and mean/median doses of other immunosuppressant drugs. Seventy-seven of 119 patients with anti-MuSK MG evaluated between January 1, 2005, and January 1, 2015, at 10 neuromuscular centers were selected for analysis after review of limited clinical data by a blinded expert panel. An additional 22 patients were excluded due to insufficient follow-up. Baseline characteristics were similar between the rituximab-treated patients (n = 24) and the controls (n = 31). Median follow-up duration was >3.5 years. At last visit, 58% (14/24) of rituximab-treated patients reached the primary outcome compared to 16% (5/31) of controls (p = 0.002). Number needed to treat for the primary outcome is 2.4. At last visit, 29% of rituximab-treated patients were taking prednisone (mean dose 4.5 mg/day) compared to 74% of controls (mean dose 13 mg/day) (p = 0.001 and p = 0.005). This study provides Class IV evidence that for patients with anti-MuSK MG, rituximab increased the probability of a favorable outcome.

Final Results from the Phase 3 Traial Areta Comparing a Novel, Extended-Release Anagrelide Formulation to Placebo in Essential Thrombocythemia Patients with Defined Risk Status

▪Background: Anagrelide hydrochloride (ana), is a well-known compound used to selectively normalize platelet counts (plc) by inhibiting megakaryocyte development and maturation. Common side-effects of licensed formulations may be largely due to peak plasma concentrations of ana and its 3OH-metabolite, whereas efficacy is proportional to the Area under the curve (AUC). A novel extended-release formulation (ana retard, AR) has superior pharmacokinetics (Petrides 2015) and has been demonstrated to be equally effective as the licensed formulation (Gisslinger 2016). Here, we investigate a "treat-early" concept in non-high risk ET patients.Study design:AR was compared to placebo in a phase 3, randomized, parallel group, multicenter, subject- and sponsor-blinded trial in patients diagnosed with ET according WHO 2008 and a defined risk status including JAK2 mutation, protein C/S or antithrombin III deficiency, factor V Leiden or prothrombin mutation, cardiovascular risk factors. The primary endpoint was time to first ET-related event adjudicated by a blinded expert panel, or progressive thrombocytosis (plc≥1000G/L or plc increase >300G/L within 3 months) requiring medical intervention. Secondary endpoints included plc response and change of risk status.Results: 146 patients were randomized and dosed (all Caucasian, mean age 43 years, 74% females), and 112 completed the first year with drop-out rates of 22% in AR and 25% in placebo. Only 49% of placebo patients vs. 74% of AR patients consented to enter the extension phase. Consequently, over the entire study duration, median exposure times differed significantly with 123 weeks for AR and 62 weeks for placebo. The primary endpoint was met in all analysis sets, with p<0,0008 and 13 vs. 26 ET related events and/or progressive thrombocytosis in the ITT analysis. The progression to high-risk status was 11,7% for AR vs. 26,1% for placebo (p<0,005). AR proofed highly efficacious in normalizing plc: within 2 weeks of therapy mean baseline plc of around 750G/L were consistently below 400G/L (83% complete, 12% partial responders). The maintenance dose was the highest tolerated dose able to maintain plc in range; for 73% of AR patients this was achieved with a single 2mg tablet given once-daily. Remaining patients received doses up to 4 tablets per day. AR showed an acceptable safety profile consistent with the SmPC of licensed ana formulations.Conclusions: Long term treatment of ET patients with defined risk status, using this novel modified-release anagrelide formulation proofed well tolerable, normalized plc in a vast majority, significantly reduced progression to high-risk status and most importantly was associated with significantly less clinical ET related events. These data have important implications for the optimal management of ET and support a "treat-early" approach.ReferencesResults of a phase I, single dose, randomized, 3-way crossover study, to assess the bioavailability of a novel anagrelide extended release (ER) formulation in comparison to a commercially available anagrelide reference product (CARP) in healthy volunteers, Petrides P, Zagrijtschuk O, Klade C, DGHO, 2015Phase 3 trial TEAM-ET in 106 high-risk Essential Thrombocythemia patients, demonstrating non-inferiority of Anagrelide Retard, a novel, extended-release anagrelide formulation, to the licensed comparatorGisslinger H, Radinoff A, Karyagina E,Kyrcz-Krzemień S, Abdulkadyrov K, Gerbutavicius R,Melikyan A, Burgstaller S, Hus M, Kłoczko J, Yablokova V, Tzvetkov N, Całbecka M, Shneyder T, Warzocha K, Jurgutis M, Kaplanov K, Hodisch J, Klade C, Buxhofer-Ausch V, European School of Hematology EHA 21st Congress, 2016 DisclosuresGisslinger:AOP Orphan Pharmaceuticals AG, Novartis, Celgene, Baxalta: Consultancy, Honoraria, Research Funding. Klade:AOP Orphan: Employment. Kyrcz-Krzemien:AOP Orphan Pharmaceuticals AG, Novartis, BMS, Medac: Honoraria. Warzocha:BMS: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Grohmann-Izay:AOP Orphan Pharmaceuticals AG: Employment. Hodisch:AOP Orphan Pharmaceuticals: Employment. Widmann:AOP Orphan Pharmaceuticals: Employment. Kralovics:Qiagen: Membership on an entity's Board of Directors or advisory committees; AOP Orphan: Research Funding. Schwarz:AOP Orphan Pharmaceuticals: Consultancy. Kiladjian:Novartis: Research Funding; AOP Orphan: Research Funding.

Computerized Diagnostic Assistant for the Automatic Detection of Pneumothorax on Ultrasound: A Pilot Study.

IntroductionBedside thoracic ultrasound (US) can rapidly diagnose pneumothorax (PTX) with improved accuracy over the physical examination and without the need for chest radiography (CXR); however, US is highly operator dependent. A computerized diagnostic assistant was developed by the United States Army Institute of Surgical Research to detect PTX on standard thoracic US images. This computer algorithm is designed to automatically detect sonographic signs of PTX by systematically analyzing B-mode US video clips for pleural sliding and M-mode still images for the seashore sign. This was a pilot study to estimate the diagnostic accuracy of the PTX detection computer algorithm when compared to an expert panel of US trained physicians.MethodsThis was a retrospective study using archived thoracic US obtained on adult patients presenting to the emergency department (ED) between 5/23/2011 and 8/6/2014. Emergency medicine residents, fellows, attending physicians, physician assistants, and medical students performed the US examinations and stored the images in the picture archive and communications system (PACS). The PACS was queried for all ED bedside US examinations with reported positive PTX during the study period along with a random sample of negatives. The computer algorithm then interpreted the images, and we compared the results to an independent, blinded expert panel of three physicians, each with experience reviewing over 10,000 US examinations.ResultsQuery of the PACS system revealed 146 bedside thoracic US examinations for analysis. Thirteen examinations were indeterminate and were excluded. There were 79 true negatives, 33 true positives, 9 false negatives, and 12 false positives. The test characteristics of the algorithm when compared to the expert panel were sensitivity 79% (95 % CI [63–89]) and specificity 87% (95% CI [77–93]). For the 20 images scored as highest quality by the expert panel, the algorithm demonstrated 100% sensitivity (95% CI [56–100]) and 92% specificity (95% CI [62–100]).ConclusionThis novel computer algorithm has potential to aid clinicians with the identification of the sonographic signs of PTX in the absence of expert physician sonographers. Further refinement and training of the algorithm is still needed, along with prospective validation, before it can be utilized in clinical practice.

What is the effect of a formalised trauma tertiary survey procedure on missed injury rates in multi-trauma patients? Study protocol for a randomised controlled trial.

BackgroundMissed injury is commonly used as a quality indicator in trauma care. The trauma tertiary survey (TTS) has been proposed to reduce missed injuries. However a systematic review assessing the effect of the TTS on missed injury rates in trauma patients found only observational studies, only suggesting a possible increase in early detection and reduction in missed injuries, with significant potential biases. Therefore, more robust methods are necessary to test whether implementation of a formal TTS will increase early in-hospital injury detection, decrease delayed diagnosis and decrease missed injuries after hospital discharge.Methods/DesignWe propose a cluster-randomised, controlled trial to evaluate trauma care enhanced with a formalised TTS procedure. Currently, 20 to 25% of trauma patients routinely have a TTS performed. We expect this to increase to at least 75%. The design is for 6,380 multi-trauma patients in approximately 16 hospitals recruited over 24 months. In the first 12 months, patients will be randomised (by hospital) and allocated 1:1 to receive either the intervention (Group 1) or usual care (Group 2). The recruitment for the second 12 months will entail Group 1 hospitals continuing the TTS, and the Group 2 hospitals beginning it to enable estimates of the persistence of the intervention. The intervention is complex: implementation of formal TTS form, small group education, and executive directive to mandate both. Outcome data will be prospectively collected from (electronic) medical records and patient (telephone follow-up) questionnaires. Missed injuries will be adjudicated by a blinded expert panel. The primary outcome is missed injuries after hospital discharge; secondary outcomes are maintenance of the intervention effect, in-hospital missed injuries, tertiary survey performance rate, hospital and ICU bed days, interventions required for missed injuries, advanced diagnostic imaging requirements, readmissions to hospital, days of work and quality of life (EQ-5D-5 L) and mortality.DiscussionThe findings of this study may alter the delivery of international trauma care. If formal TTS is (cost-) effective this intervention should be implemented widely. If not, where already partly implemented, it should be abandoned. Study findings will be disseminated widely to relevant clinicians and health funders.Trial registrationANZCTR: ACTRN12613001218785, prospectively registered, 5 November 2013Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-015-0733-y) contains supplementary material, which is available to authorized users.

The Leukocyte Antibody Prevalence Study-II (LAPS-II): a retrospective cohort study of transfusion-related acute lung injury in recipients of high-plasma-volume human leukocyte antigen antibody-positive or -negative components.

We used a multicenter retrospective cohort study design to evaluate whether human leukocyte antigen (HLA) antibody donor screening would reduce the risk of transfusion-related acute lung injury (TRALI) or possible TRALI. In the Leukocyte Antibody Prevalence Study-II (LAPS-II), we evaluated pulmonary outcomes in recipients of 2596 plasma-rich blood components (transfusable plasma and plateletpheresis) sent to participating hospitals; half of the components were collected from anti-HLA-positive donors (study arm) and half from anti-HLA-negative donors (control arm) matched by sex, parity, and blood center. A staged medical record review process was used. Final recipient diagnosis was based on case review by a blinded expert panel of pulmonary or critical care physicians. TRALI incidence was 0.59% (seven cases) in study arm recipients versus 0.16% (two cases) in control arm recipients for an odds ratio (OR) of 3.6 (95% confidence interval [CI], 0.7-17.4; p = 0.10). For possible TRALI cases (nine study arm, eight control arm), the OR was 1.2 (95% CI, 0.4-3.0; p = 0.81), and for TRALI and possible TRALI aggregated together, it was 1.7 (95% CI, 0.7-3.7; p = 0.24). Transfusion-associated circulatory overload incidence was identical in the two arms (1.17 and 1.22%, respectively; OR, 1.0; p = 1.0). TRALI incidence in recipients of anti-HLA-positive components was relatively low for a lookback study (1 in 170) and was higher than in the control arm, but did not reach significance. Based on this trend, the data are consistent with the likelihood that TRALI risk is decreased by selecting high-volume plasma components for transfusion from donors at low risk of having HLA antibodies.

Efficacy and augmentation during 6 months of double-blind pramipexole for restless legs syndrome

Background Pramipexole is an effective treatment for restless legs syndrome (RLS), but no controlled studies have lasted >12 weeks. Methods RLS patients ( N = 331) with pretreatment serum ferritin >30 ng/mL were randomly assigned to take double-blind optimized pramipexole (0.125–0.75 mg/d) or placebo for 26 weeks. The primary efficacy endpoint was change in International RLS Study Group Rating Scale (IRLS) score. Other endpoints assessed global change, symptoms, and QoL. Patients maintained symptom diaries. Cases meeting predefined criteria for suspected augmentation were reviewed by a blinded expert panel, which used a predefined algorithm. Results Among 321 patients providing post-baseline data, of whom 234 completed 26 weeks, pramipexole was more effective than placebo by multiple endpoints, including an adjusted mean IRLS score change of −13.7 vs. −11.1 ( p = 0.0077) and an IRLS responder rate (⩾50% score reduction) of 58.6% vs. 42.8% ( p = 0.0044). Efficacy showed considerable country-to-country variability. Six-month incidence of confirmed augmentation was 9.2% for pramipexole and 6.0% for placebo. The rate increased with treatment duration for pramipexole but not placebo. Treatment-related adverse events (AEs) were more likely for pramipexole than for placebo, but discontinuation due to AEs was less likely. Conclusions During a 6-month period, pramipexole was effective, safe, and generally well tolerated. Because risk of augmentation may have increased over 6 months, it should be studied in longer trials. Beginning or mild augmentation is difficult to distinguish from natural RLS fluctuation, at least in a non-iron-deficient population.

Influence of renal dysfunction on the accuracy of procalcitonin for the diagnosis of postoperative infection after vascular surgery

Procalcitonin has been advocated as a specific biomarker for bacterial infection. We performed this study to determine whether accuracy of procalcitonin for diagnosis of postoperative bacterial infection is affected by renal function after aortic surgery. Single-center prospective study. University hospital. Two hundred seventy-six patients scheduled for elective major aortic surgery. Blood samples were taken before surgery and each day over the 5-day postoperative period, and measurement of serum procalcitonin was performed. Diagnosis of infection was performed by a blinded expert panel. Renal function was assessed using an estimate of creatinine clearance with the Cockcroft formulas. Renal dysfunction was defined as a creatinine clearance <50 mL x min(-1). Infection was diagnosed in 67 patients. Seventy five patients (27%) had postoperative renal dysfunction. Procalcitonin was significantly higher in infected patients, with a peak reached at the fourth postoperative day, but it was significantly higher in patients with impaired renal function in both control and infected patients. The optimal threshold of procalcitonin markedly differed in patients with renal dysfunction compared with patients without renal dysfunction (2.57 vs. 0.80 ng x mL(-1), p < .05). The diagnostic accuracy of procalcitonin significantly increased (0.74 vs. 0.70, p < .05) when the threshold of procalcitonin was adapted to the renal function. The elevation of procalcitonin occurred 2 days before the medical team was able to diagnose infection. Procalcitonin is a valuable marker of bacterial infections after major aortic surgery, but renal function is a major determinant of procalcitonin levels and thus different thresholds should be applied according to renal function impairment.

Serial endoscopy in azoxymethane treated mice using ultra-high resolution optical coherence tomography

Purpose: Optical coherence tomography (OCT) is a minimally invasive, depth-resolved imaging tool that can be implemented in a small diameter endoscope for imaging mouse models of colorectal cancer (CRC). In this study, we utilized ultrahigh resolution (UHR) OCT to serially image the lower colon of azoxymethane (AOM) treated A/J mouse models of CRC in order to monitor the progression of neoplastic transformations and determine if OCT is capable of identifying early disease. Experimental Design: Thirteen AOM treated A/J and two control A/J mice were surveyed at four timepoints (8, 14, 22, and 26 weeks post AOM treatment) using a 2.0 mm diameter UHR OCT endoscopic system with 3.2 µm axial and 4.4 µm lateral resolution. Histological samples obtained at the final timepoint served as the diagnostic reference. A blinded expert panel of mouse colon pathologists provided diagnoses from the OCT images based on criteria developed from a separate training set of OCT images. Panel results were compared to histological diagnoses assigned by a blinded pathologist. Results: At the final imaging timepoint, 95% of adenomas and 23% of gastrointestinal neoplasias (38% protruding GINs and 9% non-protruding GINs) were correctly diagnosed. The panel identified 68% of disease foci (95% adenoma, 76% protruding GINs, and 13% non-protruding GINs). Over the OCT imaging timepoints, disease progression followed a typical succession, with normal or GIN preceding adenoma. Conclusions: Endoscopic UHR OCT enabled accurate diagnosis of adenomas, identification of protruding GIN, and non-destructive visualization of CRC progression, providing a tool for cancer research in animal models.

Radiology Residents’ On-Call Interpretation of Chest Radiographs for Congestive Heart Failure

This study was designed to evaluate the performance of radiology residents in interpreting emergency department (ED) chest radiographs for congestive heart failure and to characterize the factors associated with a subsequent amended interpretation by an attending radiologist. We retrospectively reviewed all amended reports for ED chest radiographs between January 2004 and July 2005 and identified those with discrepant interpretations regarding the diagnosis of congestive heart failure. A total of 1.9% (476 of 24,600) of chest radiographs were amended over the study period. Forty-eight patients (75% female, mean age 66 years) whose chest radiograph was amended for the diagnosis of congestive heart failure and were available for review formed the study population. A control group of 35 patients (69% female, mean age 67 years) were individually matched to a convenience subset of patients by age, gender, clinical indication, and radiographic projection. Chest radiographs were in the anteroposterior projection in 62% (30 of 48) of study patients and 60% (21 of 35) of controls. A blinded expert panel of three board-certified cardiothoracic radiologists jointly reviewed each chest radiograph for the presence or absence of congestive heart failure and its specific radiographic findings. The expert panel diagnosed congestive heart failure in 19% (9 of 48) of study patients and in 23% (8 of 35) of controls (P = .65). When present, congestive heart failure was mild to moderate in severity in both the study and control groups (P = 1.00). There was a significant difference in the expert panel agreement between the attending versus the resident interpretation (65% versus 35%, P = .008), for the study group. This resulted in fair agreement (kappa = 0.29) between the expert panel and the attending interpretation and no agreement (kappa = -0.29) between the expert panel and the resident interpretation. In contrast, the expert panel agreed with the joint resident/attending interpretation in 83% (29 of 35) of controls, yielding substantial agreement (kappa = 0.72). Interpretation of chest radiographs for congestive heart failure by radiology residents has a low error rate. The majority of chest radiographs with discrepant resident and attending interpretations were portable films of female patients with subtle radiographic findings of congestive heart failure, and were inherently difficult to interpret.

Assessment of the Accuracy of Procalcitonin to Diagnose Postoperative Infection after Cardiac Surgery

Cardiopulmonary bypass induces a nonspecific inflammatory response. Procalcitonin has been advocated as a specific biomarker for infection. The authors studied the accuracy of procalcitonin to diagnose postoperative infection after cardiac surgery and compared it with those of C-reactive protein, white blood cell count, and interleukins 6 and 8. The authors prospectively included 100 patients scheduled to undergo elective cardiac procedures with cardiopulmonary bypass. Blood samples were taken before surgery and each day over the 7-day postoperative period, and measurement of procalcitonin, C-reactive protein, white blood cell count, and interleukins 6 and 8 were performed. Diagnosis of infection was performed by a blinded expert panel. Data are expressed as value [95% confidence interval]. Infection was diagnosed in 16 patients. Procalcitonin was significantly higher in infected patients, with a peak reached on the third postoperative day. Only the areas under the receiver operating curve of procalcitonin (0.88 [0.71-0.95]) and C-reactive protein (0.72 [0.58-0.82]) were significantly different from the no-discrimination curve, and that of procalcitonin was significantly different from those of C-reactive protein, white blood cell count, and interleukins 6 and 8. A procalcitonin value greater than 1.5 ng/ml beyond the second day diagnosed postoperative infection with a sensitivity of 0.93 [0.70-0.99] and a specificity of 0.80 [0.70-0.87]. Procalcitonin was significantly higher in patients who died (27.5 [1.65-40.5] vs. 1.2 [0.7-1.5] ng/ml; P < 0.001). Procalcitonin is a valuable marker of bacterial infections after cardiac surgery.

Posaconazole vs Standard Azole (FLU/ITRA) Therapy for Prophylaxis of Invasive Fungal Infections (IFIs) among High-Risk Neutropenic Patients: Results of a Randomized, Multicenter Trial.

Background: Patients with severe and prolonged neutropenia are at high-risk of developing life-threatening IFIs. Despite current treatment option, IFIs are difficult to treat and frequently associated with high mortality rates. Antifungal prophylaxis has shown benefits in high-risk populations and is a standard practice in many institutions. We compared Posaconazole (POS), a new broad-spectrum triazole, vs Standard Azoles for the prevention of IFIs in patients with a new diagnosis or first relapse of acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) being treated with intensive chemotherapy.Methods: Patients in this randomized, evaluator-blinded, active controlled, multi-center study received oral POS (200mg tid) or oral Standard Azoles (either Fluconazole [FLU 400mg qd] or Itraconazole solution [ITRA 200mg bid]) with each cycle of chemotherapy until complete remission or for up to a maximum of 12 weeks. The primary efficacy end point was the comparison of the incidence of IFIs during the treatment phase (7 days after last dose) as adjudicated by the blinded expert panel based on EORTC/MSG criteria. The incidence of IFIs 100 days after randomization and the clinical outcome at the end of the treatment phase were also compared. Treatment failure was defined as presence of proven or probable IFIs, use of >3 days of empirical systemic antifungal treatment, use of >3 consecutive days or a total of 10 or more days of IV study drug (or alternative formulation for POS), discontinuation due to an adverse event related to study drug or lost to follow-up during treatment.Results: 602 patients were enrolled (304 POS, 298 Standard Azole [240 FLU, 58 ITRA]). The incidence of proven/probable IFIs was lower with POS prophylaxis (see table). The overall mortality was 49 (16%) vs 67 (22%) for patients in the POS and Standard Azoles arms respectively. Analysis of time to death (all cause mortality) within 100 days post randomization yielded a P-value of 0.035, indicating a significant survival benefit in favor of POS. Twenty-one (21) deaths due to IFIs occurred during the study (POS 5, Standard Azoles 16, P = 0.012). Treatment failures were fewer in the POS arm vs Standard Azoles arm (36% vs 46%, P = 0.0091). Safety and tolerability were comparable.Conclusions: In this study, POS was superior to the use of a Standard Azoles (FLU or ITRA) in preventing IFIs and in preventing aspergillosis, in high-risk neutropenic patients with AML or MDS undergoing intensive chemotherapy. Patients receiving POS experienced a significant survival benefit.POS N=304FLU/ITRA N=298Proven/Probable IFIsn (%)n (%)P-valueAll IFIs during Treatment Phase7 (2)25 (8)0.0009Aspergillus during Treatment Phase2 (1)20 (7)0.0001All IFIs within 100 days post-randomization14 (5)33 (11)0.0031