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Khaled M Musallam,1 Ali T Taher,2 Antonis Kattamis,3 Kevin HM Kuo,4 Sujit Sheth,5 Maria Domenica Cappellini6 1Thalassemia Center, Burjeel Medical City, Abu Dhabi, United Arab Emirates; 2Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon; 3First Department of Pediatrics, National and Kapodistrian University of Athens, Athens, Greece; 4Division of Hematology, University of Toronto, Toronto, ON, Canada; 5Division of Hematology and Oncology, Department of Pediatrics, Weill Cornell Medicine, New York, NY, USA; 6Department of Clinical Sciences and Community, University of Milan, Ca’ Granda Foundation IRCCS Maggiore Policlinico Hospital, Milan, ItalyCorrespondence: Maria Domenica Cappellini, Department of Clinical Sciences and Community, University of Milan, Ca’ Granda Foundation IRCCS Maggiore Policlinico Hospital, Milan, 20122, Italy, Tel + 39 02 5503 3752, Email maria.cappellini@unimit.itAbstract: Over the past decade, evidence has been mounting on the detrimental clinical sequelae of untreated anemia in patients with non-transfusion-dependent β-thalassemia (NTDT). There are no pharmacologic agents that are specifically approved for the management of anemia in NTDT, and available options such as splenectomy, transfusion therapy, and hydroxyurea each come with their own shortcomings, especially for long-term use. Luspatercept is an erythroid maturation agent that has been evaluated in a Phase 2, randomized trial and showed a significant benefit in raising hemoglobin level by at least 1 g/dL in adults with NTDT and a baseline hemoglobin level ≤ 10 g/dL. These data led to luspatercept’s approval by the European Commission for the treatment of anemia in adults with NTDT and presents the first evidence-based approach for a novel agent that is able to ameliorate anemia in this patient population.Keywords: anemia, ineffective erythropoiesis, iron, management, thalassemia, transfusion

Kristen H Kuo,1,2 Sidrah Anjum,1 Brian Nguyen,1,3,4 Jeffrey L Marx,1,2 Shiyoung Roh,1,2 David J Ramsey1,2 1Department of Ophthalmology, Lahey Hospital & Medical Center, Peabody, MA, USA; 2Department of Ophthalmology, Tufts University School of Medicine, Boston, MA, USA; 3Tufts University School of Dental Medicine, Boston, MA, USA; 4Heller School for Social Policy and Management, Brandeis University, Waltham, MA, USACorrespondence: David J RamseyDepartment of Ophthalmology, Lahey Hospital & Medical Center, Beth Israel Lahey Health, 1 Essex Center Drive, Peabody, MA, 01960, USAEmail David.J.Ramsey@lahey.orgPurpose: We conducted a cross-sectional study to assess the utilization of a tele-ophthalmology screening program in a low-risk, suburban population of patients with diabetes.Methods: A total of 214 diabetic patients without previously documented diabetic retinopathy (DR) underwent point-of-care non-mydriatic fundus photography through their primary care providers at five Beth Israel Lahey Health locations. The characteristics of the patients who received remote screening were compared with those patients who were eligible for screening but did not take part in the program. Time-driven activity-based costing (TDABC) was implemented to examine the cost of screening by tele-ophthalmology compared with in-person examinations.Results: Tele-ophthalmology screening was more likely to be provided for patients who were younger (OR 0.985; 95% CI 0.973– 0.997, p=0.016), who were obese (OR 2.04; 95% CI: 1.47– 2.84, p=0.008), who had an HbA1c above 8.0% (OR 1.60; 95% CI: 1.13– 2.26, p=0.031), or who had an eye examination in the past year (OR 5.55; 95% CI: 3.89– 7.92, p< 0.001). Those patients newly diagnosed with DR because of the program were more likely to have diabetic nephropathy (OR 7.79; 95% CI: 1.73– 35.05, p=0.007). TDABC identified a health system cost-savings of between $8 and $29 per patient screened by tele-ophthalmology compared with the cost of in-person eye examinations.Conclusion: Tele-ophthalmology presents an opportunity to reduce the costs of screening patients without prior evidence of DR, especially those who have completed a comprehensive eye examination within the prior year.Keywords: telemedicine, tele-ophthalmology, diabetes, diabetic retinopathy, screening, non-mydriatic fundus photography

In this study, our objective was to assess the performance of two deep learning-based hippocampal segmentation methods, SynthSeg and TigerBx, which are readily available to the public. We contrasted their performance with that of two established techniques, FreeSurfer-Aseg and FSL-FIRST, using three-dimensional T1-weighted MRI scans (n = 1447) procured from public databases. Our evaluation focused on the accuracy and reproducibility of these tools in estimating hippocampal volume. The findings suggest that both SynthSeg and TigerBx are on a par with Aseg and FIRST in terms of segmentation accuracy and reproducibility, but offer a significant advantage in processing speed, generating results in less than 1 min compared with several minutes to hours for the latter tools. In terms of Alzheimer's disease classification based on the hippocampal atrophy rate, SynthSeg and TigerBx exhibited superior performance. In conclusion, we evaluated the capabilities of two deep learning-based segmentation techniques. The results underscore their potential value in clinical and research environments, particularly when investigating neurological conditions associated with hippocampal structures., (© 2024 John Wiley & Sons Ltd.)

Background: Polypharmacy for treatment of depression has been increasing in Taiwan., Methods: Individuals having depressive disorders were identified in a national database for healthcare services and followed up for 5 years. The mean dosage of antidepressants, antipsychotics, mood stabilizers, and sedative-hypnotics was calculated; the associations between the exposure dosage to different psychotropic medications and patients' overall death and death due to cardiovascular diseases (CVD) and suicide were examined., Results: A total of 400,042 individuals with depressive disorders (63.8% women) were identified. Compared with those with no exposure to antidepressants, patients prescribed antidepressants had decreased mortality. Use of antipsychotics had a dose-related increase in overall mortality risk compared to no exposure group. Contrarily, depressed patients taking sedative-hypnotics had decreased overall and CVD mortality compared to no exposure group, with the most prominent decrease in CVD mortality of up to 54.9% for those in the moderate exposure group (hazard ratio: 0.451, 95% confidence interval: 0.405-0.503). A moderate or high dose of antidepressants or sedative-hypnotics was shown to be associated with a significantly increased mortality for suicide compared to those with no exposure., Conclusions: Antidepressant and sedative-hypnotic use was associated with decreased all-cause and CVD-related mortality and use of antipsychotics was associated with a dose-related increase in mortality risk. Future studies are needed to further clarify the involved mechanisms and benefits and risks should be carefully weighed when prescribing psychotropic medications in patients with depressive disorders., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study aims to evaluate an AI model designed to automatically classify skull fractures and visualize segmentation on emergent CT scans. The model's goal is to boost diagnostic accuracy, alleviate radiologists' workload, and hasten diagnosis, thereby enhancing patient outcomes. Unique to this research, both pediatric and post-operative patients were not excluded, and diagnostic durations were analyzed. Our testing dataset for the observer studies involved 671 patients, with a mean age of 58.88 years and fairly balanced gender representation. Model 1 of our AI algorithm, trained with 1499 fracture-positive cases, showed a sensitivity of 0.94 and specificity of 0.87, with a DICE score of 0.65. Implementing post-processing rules (specifically Rule B) improved the model's performance, resulting in a sensitivity of 0.94, specificity of 0.99, and a DICE score of 0.63. AI-assisted diagnosis resulted in significantly enhanced performance for all participants, with sensitivity almost doubling for junior radiology residents and other specialists. Additionally, diagnostic durations were significantly reduced (p < 0.01) with AI assistance across all participant categories. Our skull fracture detection model, employing a segmentation approach, demonstrated high performance, enhancing diagnostic accuracy and efficiency for radiologists and clinical physicians. This underlines the potential of AI integration in medical imaging analysis to improve patient care., (© 2024. The Author(s).)

Acute pyelonephritis is a common infection of the upper urinary tract that affects approximately 250,000 adults in the United States. Individuals with acute pyelonephritis require hospitalization and intravenous antimicrobial therapy. Diagnoses of acute pyelonephritis are made on the basis of clinical and laboratory findings. Individuals with complex or severe acute pyelonephritis undergo contrast-enhanced computed tomography (CT) for the diagnosis and assessment of perirenal abnormalities. However, extrarenal manifestations, such as periportal edema and gallbladder wall thickening, may complicate the diagnostic process. We report the case of a 42-year-old woman who presented with fever, dysuria, and flank pain-the hallmarks of urosepsis. CT results confirmed acute pyelonephritis accompanied by periportal edema and elevated levels of hepatic enzymes and C-reactive protein. Despite antibiotic intervention, febrile episodes persisted for 4 days and abated over a fortnight. The patient's blood and urine cultures yielded negative results, which may be attributed to her prior antimicrobial treatment. Recognition of extrarenal signs in acute pyelonephritis is crucial for obtaining accurate diagnoses and understanding their clinical implications.

Insight into effect of deuterium isotopes on organic near-IR (NIR) emitters was explored by the use of self-assembled Pt(II) complexes H-3-f and HPh-3-f, and their deuterated analogues D-3-f and DPh-3-f, respectively (Scheme 2). In vacuum deposited thin film, albeit having nearly identical emission spectral feature maximized at ~810 nm, H-3-f and D-3-f exhibit remarkable difference in photoluminescence quantum yield (PLQY) of 29 % and 50 %, respectively. Distinction in PLQY is also observed for HPh-3-f (800 nm, 50 %) and DPh-3-f (798 nm, 67 %). We then elucidated the theoretical differences in the impact on near-infrared (NIR) luminescence between Pt(II) complexes and organic small molecules upon deuteration. The results establish a general guideline for the deuteration on NIR emission efficiency. From a perspective of practical application, NIR OLEDs based on D-3-f and DPh-3-f emitters attain EQE max of 15.5 % (radiance 31,287 mW Sr -1  m -2 ) and 16.6 % (radiance of 32,279 mW Sr -1  m -2 ) at 764 nm and 796 nm, respectively, both of which set new records for NIR OLEDs of >750 nm., (© 2024 Wiley-VCH GmbH.)

Patients with schizophrenia have a high mortality risk, and the role of antipsychotic medications remains inconclusive. In an aging society, older patients with schizophrenia warrant increased attention. This study investigated the association of antipsychotic medication dosages with mortality in patients with schizophrenia by using data from Taiwan's National Health Insurance Research Database from 2010 to 2014. This study included 102,964 patients with schizophrenia and a subgroup of 6433 older patients in addition to an age- and sex-matched control group. The findings revealed that among patients with schizophrenia, the no antipsychotic exposure group had the highest mortality risk (3.61- and 3.37-fold higher risk for overall and cardiovascular mortality, respectively) in the age- and sex-adjusted model, followed by the high, low, and moderate exposure groups. A similar pattern was observed in the older patients with schizophrenia. High exposure to antipsychotics was associated with the highest risks of overall and cardiovascular mortality (3.01- and 2.95-fold higher risk, respectively). In conclusion, the use of antipsychotics can be beneficial for patients with schizophrenia with recommended exposure levels being low to moderate. In older patients, high antipsychotic exposure was associated with the highest mortality risk, indicating that clinicians should be cautious when administering antipsychotic medications to such patients.

Photomemristors have been regarded as one of the most promising candidates for next-generation hardware-based neuromorphic computing due to their potentials of fast data transmission and low power consumption. However, intriguingly, so far, photomemristors seldom display truly nonvolatile memory characteristics with high light sensitivity. Herein, we demonstrate ultrasensitive photomemristors utilizing two-dimensional (2D) Ruddlesden-Popper (RP) perovskites with a highly polar donor-acceptor-type push-pull organic cation, 4-(5-(2-aminoethyl)thiophen-2-yl)benzonitrile + (EATPCN + ), as charge-trapping layers. High linearity and almost zero-decay retention are observed in (EATPCN) 2 PbI 4 devices, which are very distinct from that of the traditional 2D RP perovskite devices consisting of nonpolar organic cations, such as phenethylamine + (PEA + ) and octylamine + (OA + ), and traditional 3D perovskite devices consisting of methylamine + (MA + ). The 2-fold advantages, including desirable spatial crystal arrangement and engineered energetic band alignment, clarify the mechanism of superior performance in (EATPCN) 2 PbI 4 devices. The optimized (EATPCN) 2 PbI 4 photomemristor also shows a memory window of 87.9 V and an on/off ratio of 10 6 with a retention time of at least 2.4 × 10 5 s and remains unchanged after >10 5 writing-reading-erasing-reading endurance cycles. Very low energy consumptions of 1.12 and 6 fJ for both light stimulation and the reading process of each status update are also demonstrated. The extremely low power consumption and high photoresponsivity were simultaneously achieved. The high photosensitivity surpasses that of a state-of-the-art commercial pulse energy meter by several orders of magnitude. With their outstanding linearity and retention, rabbit images have been rebuilt by (EATPCN) 2 PbI 4 photomemristors, which truthfully render the image without fading over time. Finally, by utilizing the powerful ∼8 bits of nonvolatile potentiation and depression levels of (EATPCN) 2 PbI 4 photomemristors, the accuracies of the recognition tasks of CIFAR-10 image classification and MNIST handwritten digit classification have reached 89% and 94.8%, respectively. This study represents the first report of utilizing a functional donor-acceptor type of organic cation in 2D RP perovskites for high-performance photomemristors with characteristics that are not found in current halide perovskites.

Three organic conjugated small molecules, DTA-DTPZ , Cz-DTPZ , and DTA-me-DTPZ comprising an antiaromatic 5,10-ditolylphenazine (DTPZ) core and electron-donating peripheral substituents with high HOMOs (-4.2 to -4.7 eV) and multiple reversible oxidative potentials are reported. The corresponding films sandwiched between two electrodes show unipolar and switchable hysteresis current-voltage ( I - V ) characteristics upon voltage sweeping, revealing the prominent features of nonvolatile memristor behaviors. The numerical simulation of the I - V curves suggests that the carriers generated by the oxidized molecules lead to the increment of conductance. However, the accumulated carriers tend to deteriorate the device endurance. The electroactive sites are fully blocked in the dimethylated molecule DTA-me-DTPZ , preventing the irreversible electrochemical reaction, thereby boosting the endurance of the memristor device over 300 cycles. Despite the considerable improvement in endurance, the decrement of on/off ratio from 10 5 to 10 1 after 250 cycles suggests that the excessive charge carriers (radical cations) remains a problem. Thus, a new strategy of doping an electron-deficient material, CN-T2T , into the unipolar active layer was introduced to further improve the device stability. The device containing DTA-me-DTPZ : CNT2T (1:1) blend as the active layer retained the endurance and on/off ratio (∼10 4 ) upon sweeping 300 cycles. The molecular designs and doping strategy demonstrate effective approaches toward more stable metal-free organic conjugated small-molecule memristors.

ConspectusDesigning bright and efficient near-infrared (NIR) emitters has drawn much attention due to numerous applications ranging from biological imaging, medical therapy, optical communication, and night-vision devices. However, polyatomic organic and organometallic molecules with energy gaps close to the deep red and NIR regime are subject to dominant nonradiative internal conversion (IC) processes, which drastically reduces the emission intensity and exciton diffusion length of organic materials and hence hampers the optoelectronic performances. To suppress nonradiative IC rates, we suggested two complementary approaches to solve the issues: exciton delocalization and molecular deuteration. First, exciton delocalization efficiently suppresses the molecular reorganization energy through partitioning to all aggregated molecules. According to the IC theory together with the effect of exciton delocalization, the simulated nonradiative rates with the energy gap Δ E = 10 4 cm -1 decrease by around 10 4 fold when the exciton delocalization length equals 5 (promoting vibronic frequency ω l = 1500 cm -1 ). Second, molecular deuterations reduce Franck-Condon vibrational overlaps and vibrational frequencies of promoting modes, which decreases IC rates by 1 order of magnitude in comparison to the rates of nondeuterated molecules under Δ E of 10 4 cm -1 . Although deuteration of molecules has long been attempted to increase emission intensity, the results have been mixed. Here, we provide a robust derivation of the IC theory to demonstrate its validity, especially to emission in the NIR region.The concepts are experimentally verified by the strategic design and synthesis of a class of square-planar Pt(II) complexes, which form crystalline aggregates in vapor deposited thin films. The packing geometries are well characterized by the grazing angle X-ray diffraction (GIXD), showing domino-like packing arrangements with the short ππ separation of 3.4-3.7 Å. Upon photoexcitation, such closely packed assemblies exhibit intense NIR emission maximized in the 740-970 nm region through metal-metal-to-ligand charge transfer (MMLCT) transition with unprecedented photoluminescent quantum yield (PLQY) of 8-82%. To validate the existence of exciton delocalization, we applied time-resolved step-scan Fourier transform UV-vis spectroscopy to probe the exciton delocalization length of Pt(II) aggregates, which is 5-9 molecules (2.1-4.5 nm) assuming that excitons mainly delocalized along the direction of ππ stacking. According to the dependence of delocalization length vs simulated IC rates, we verify that the observed delocalization lengths contribute to the high NIR PLQY of the aggregated Pt(II) complexes. To probe the isotope effect, both partially and completely deuterated Pt(II) complexes were synthesized. For the case of the 970 nm Pt(II) emitter, the vapor deposited films of per-deuterated Pt(II) complexes exhibit the same emission peak as that of the nondeuterated one, whereas PLQY increases ∼50%. To put the fundamental studies into practice, organic light-emitting diodes (OLEDs) were fabricated with a variety of NIR Pt(II) complexes as the emitting layer, showing the outstanding external quantum efficiencies (EQEs) of 2-25% and the remarkable radiances 10-40 W sr -1 m -2 at 740-1002 nm. The prominent device performances not only successfully prove our designed concept but also reach a new milestone for highly efficient NIR OLED devices.This Account thus summarizes our approaches about how to boost the efficiency of the NIR emission of organic molecules from an in-depth fundamental basis, i.e., molecular design, photophysical characterization, and device fabrication. The concept of the exciton delocalization and molecular deuteration may also be applicable to a single molecular system to achieve efficient NIR radiance, which is worth further investigation in the future.

Background: This study describes the implementation of an electronic medical record (EMR)-based initiative aimed at identifying and reducing the number of patients with diabetic retinopathy (DR) lost to follow-up (LTF)., Method: Providers were enlisted to review the EMRs and re-engage patients with DR seen 1 year prior and who had not returned for care within the past 6 months. Binary logistic regression analysis was used to identify demographic, clinical and sociomedical factors associated with being LTF, as well as those predictive of re-engagement., Results: Out of 673 patients with DR, 78 (12%) were identified as LTF. Patients LTF were more likely to be younger (p = 0.001) and have poorly controlled haemoglobin A1c (HbA1c ≥ 8%, p = 0.04) and cholesterol (LDL ≥ 100 mg/dL, p < 0.001) levels. These patients were also more likely to have completed fewer ophthalmology appointments (p < 0.001), and less likely to have had retinal imaging within the last year (p < 0.001). Charts reviewed 1 month after the EMR-based initiative revealed that 22 patients (28%) had been successfully re-engaged by providers, while 56 patients (72%) remained LTF. History of prior treatment for DR was associated with re-engagement by providers (p = 0.04). One month following the provider-based intervention, the LTF rate dropped to 8.3%, and by 1 year only 3.6% of the patients remained LTF., Conclusions: Electronic medical record-based tools can successfully identify DR patients as being LTF, offering an opportunity for providers to re-engage patients in a timely manner. Future studies are needed to determine the long-term impact of patient re-engagement on DR outcomes and efficiency of clinical practice., (© 2022 College of Optometrists.)

A new dioxasilepine and aryldiamine hybrid material DPSi-DBDTA is designed to act as the electron-blocking layer (EBL) for vacuum-processed organic photodetector (OPD). The O-Si-O-linked cyclic structure leads DPSi-DBDTA to have dipolar character, high LUMO, and good thermal and morphology stability suitable for vacuum deposition. An initial trial with C 60 -based single active layer OPD device manifests the superior capability of DPSi-DBDTA for dark current suppression compared to the typical aryldiamines. Here, the bare and MoO 3 -doped DPSi-DBDTA is further examined as EBLs for the visible light responsive OPD comprising DTDCPB /C 70 bulk heterojunction (BHJ) as the active layer. In sync with the result of C 60 -based OPD, the low dark current density and high specific detectivity D * (7.085 × 10 12 cm Hz 1/2 W -1 ) are achieved. The device with 5% MoO 3 -doped EBL can exhibit a wide linear dynamic range (LDR) up to 154.166 dB, which is attributed to suppression of both dark current density and carrier recombination. Additionally, the devices also manifest fast time-resolved performance in both frequency and transient response measurements. Especially for the device with 20% MoO 3 -doped EBL, a wide cutoff frequency response 692.047 kHz and record-high transient response demonstrating ≤0.683 μs for transient photovoltage (TPV) and ≤0.478 μs for transient photocurrent (TPC) have been realized, which is possibly owing to the balance of mobility that mitigates the damage from traps. Such submicrosecond response is comparable with the state-of-the-art perovskite-PDs and Si-PDs.

Background: The performance of chest radiography-based age and sex prediction has not been well validated. We used a deep learning model to predict the age and sex of healthy adults based on chest radiographs (CXRs)., Methods: In this retrospective study, 66,643 CXRs of 47,060 healthy adults were used for model training and testing. In total, 47,060 individuals (mean age ± standard deviation, 38.7 ± 11.9 years; 22,144 males) were included. By using chronological ages as references, mean absolute error (MAE), root mean square error (RMSE), and Pearson's correlation coefficient were used to assess the model performance. Summarized class activation maps were used to highlight the activated anatomical regions. The area under the curve (AUC) was used to examine the validity for sex prediction., Results: When model predictions were compared with the chronological ages, the MAE was 2.1 years, RMSE was 2.8 years, and Pearson's correlation coefficient was 0.97 ( p < 0.001). Cervical, thoracic spines, first ribs, aortic arch, heart, rib cage, and soft tissue of thorax and flank seemed to be the most crucial activated regions in the age prediction model. The sex prediction model demonstrated an AUC of >0.99., Conclusion: Deep learning can accurately estimate age and sex based on CXRs.

Stenotic lesion rigidity (SLR) has an unclear influence on the outcome of percutaneous transluminal angioplasty and stenting (PTAS) for intracranial arterial stenosis. This study evaluated the outcome of PTAS and the relationship of vertebrobasilar SLR to features on vessel wall MRI (VW-MRI) for identifying pathologies of vertebrobasilar stenosis (VBS) and evaluating PTAS outcome. We retrospectively evaluated the results of PTAS in 31 patients with severe VBS. Stenotic lesions were classified as soft (based on predilatation pressure [PP] ≦ 4 atm) in 15 patients or hard (PP >4 atm) in 16 patients. We examined the relationship of SLR to clinical and MR findings. Patients with hard vs soft lesions had atherosclerosis (8/16 [50.0%] vs 2/15 [13.3%]), dissection (0/16 [0.0%] vs 12/15 [80.0%]), and dissection in atherosclerosis (8/16 [50.0%] vs 1/15 [6.7%], P < 0.0001); high intensity signal on the T1WI of VW-MRI (5/16 [31.3%] vs 14/15 [93.3%]) and iso- to low intensity signal (11/16 [68.7%] vs 1/15 [6.7], P = 0.001), and significant in-stent restenosis (>50%) in 5/15 (33.3%) vs 0/15 (0.0%) (P = 0.0421) in the 30 patients who successfully completed PTAS. Vertebrobasilar SLR correlated well with lesion etiology, findings on VW-MRI, and PTAS outcome. Patients with hard stenotic lesions need close follow-up after PTAS.

There have been significant changes in the way Autism has been defined especially in the last decade. The changes encompass criteria over a spectrum rather than individual diagnoses based on clusters of criteria. With these changes, there has been a push for earlier screening and diagnosis to be made to ensure individual impacted by the deficits have ample time and opportunity to receive the services they need. Additionally, with the changes that have come up, screening tools and assessments have also been changed and improved to assist with the increasing demand of early screening. Screeners have been created to help in primary care settings so physicians can gauge the severity of symptoms and refer patients to the appropriate resources. The assessment and diagnostic process for Autism involves a large battery including parental interviews and forms, the ADOS-II, and a multitude of other intellectual assessments to get a full picture of what the individual is experiencing. Once an individual is diagnosed with Autism, the interventionist team, physicians, and clinicians assist the family in finding the appropriate resources and treatment plan. There are several evidence-based therapies that exist that have been effective in improving the quality of life of individuals with Autism Spectrum Disorder diagnoses. Although several interventions and therapies exist, there are some potential interventions some use that need to more research to know how truly effective they are., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2020 Translational Pediatrics. All rights reserved.)

Many technological innovations have changed the traditional practice of medical education and clinical practice. Whole slide imaging (WSI) technology provided an unique way of viewing conventional glass slides in histology and pathology laboratories. The WSI technology digitalized glass slide images and made them readily accessible via the Internet using tablets or computers. Users utilized the pan-and-zoom function to view digital images of slides, also referred to as the virtual microscope (VM), simulating use of an optical microscope (OM). Several articles have reported various outcomes on the utility of VM in teaching laboratories. Recently, the Royal College of Physicians and Surgeons of Canada certification examinations for anatomical pathologists ha completely adopted VM for the national licensing examination. To better inform medical educators, there is an urgent need for more structured reviews to draw evidence-based conclusions on the effectiveness of VM and learner's perceptions, in comparison to OM. The current study provides a descriptive summary of published outcomes using the systematic review approach. In conclusion, medical students' performance was improved with adoption of VM into the curriculum and recognized as a preferred learning modality, compared to OM. On the contrary, resident learners' performance was comparable between using OM and VM, with OM being the favored slide-viewing modality., (© 2018 American Association of Anatomists.)

Background: We aimed to examine the differences in the cost distributions, service use, and mortality outcomes, across major psychiatric disorders in Taiwan., Method: A national cohort of adult patients (n = 68,068) who had newly received a diagnosis of schizophrenia, bipolar disorder, and major depressive disorder (MDD) was identified from the National Health Insurance Research Database and followed for the subsequent three years. Variations in the 1-year and 3-year healthcare cost distributions and mortality outcomes were examined according to age group (18-64 years, ≥65 years) and diagnosis., Results: Regardless of age group, individuals with schizophrenia had the highest total and psychiatric healthcare costs. Healthcare costs for psychiatric services accounted for 84.25%, 60%, and 29.62% of the 1-year total healthcare costs for younger patients with a diagnosis of schizophrenia, bipolar disorder, and MDD, respectively. Psychiatric inpatient care costs constituted a major part of the 1-year psychiatric healthcare costs, e.g., 85.86% for schizophrenia patients aged 18-64 years, while psychiatric medication costs contributed to a relatively smaller part. For those older than 65 years, costs of other specialties for comorbid physical conditions were more prominent., Limitations: The perspective of the current analysis was limited to healthcare services, and we were not able to analyse wider economic impacts., Conclusions: Psychiatric inpatient care costs contributed to a significant share of psychiatric expenditures, emphasizing the need of developing strategies to reduce rehospitalisations. For those aged 65 years or older, efforts to improve interdisciplinary service care for comorbid physical conditions may be required., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Plasma membrane (PM) of smooth muscle cells hosts channel molecules regulating the flow of various ions. An intact architecture of PM is essential to orchestrate proper channel functions in order to complete agonist-mediated contraction, which includes Ca 2+ release from the sarcoplasmic reticulum (SR) to initiate contraction, and subsequent Ca 2+ refilling into SR through PM to sustain muscle contraction. The Junctional Complex (JC), comprising of junctional SR, and its apposing PM and neighboring caveolae, provides a quasi-enclosed microdomain housing receptors as well as ion channels and also restricting ion diffusions into the cytosol so the cell achieves optimal performance. The spatial arrangement of the JC is believed to ensure an uninterrupted Ca 2+ cycling route. Full understanding of the functional role of the JC is the key to elucidating the contractile mechanisms of vascular smooth muscle and the physiological function of vessel contraction. The JC can be further divided into two sub-divisions, namely the PM-SR and caveolar regions. Previously, we demonstrated the role of the PM-SR region in the initiation of muscle contraction using pharmacological tools on the inferior vena cava (IVC) of rabbit. In the current study, we further dissected the caveolar region using a cholesterol-disrupting agent to investigate the role of the caveolar region. We conclude that disruption of the caveolar region in rabbit IVC smooth muscle results in augmented muscle contraction in response to adrenergic stimulation and the altered Ca 2+ signaling may underlie the augmented contractility. Anat Rec, 302:186-192, 2019. © 2018 Wiley Periodicals, Inc., (© 2018 Wiley Periodicals, Inc.)

There is a lack of clarity in terms of cost-effectiveness and cost-utility comparisons across different outpatient (OPD) follow-up patterns in discharged patients with bipolar disorder (BD). In this study, adult patients hospitalised for BD treatment (n = 1,591) were identified from the National Health Insurance Research Database in Taiwan. With survival as the effectiveness measure and quality-adjusted life years (QALYs) as the utility measure, a cost-effectiveness and cost-utility analysis was conducted over the 3-year follow-up period by post-discharge frequency of OPD visits. Compared to those making 1-7, 8-12 and 18 or more OPD visits, BD patients making 13-17 OPD visits within the first year after discharge had the lowest psychiatric and total healthcare costs over the follow-up period. With survival status as the effectiveness outcome, making 13-17 OPD visits was more likely to be the cost-effective option, as revealed by incremental cost-effectiveness ratios. Cost-utility analysis demonstrated that having 13-17 OPD visits was probably the more cost-effective option when considering QALYs; for instance, if society was willing to pay NTD1.5 million for one additional QALY, there was a 75.2% (psychiatric costs) to 77.4% (total costs) likelihood that 13-17 OPD visits was the most cost-effective option. In conclusion, post-discharge OPD appointments with a frequency of 13-17 visits within the first year were associated with lower psychiatric and total healthcare costs in the subsequent 3 years. Having an adequate outpatient follow-up frequency was likely to be cost-effective in the management of discharged patients with BD in this real-world setting., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Our phase I, open-label, multi-center, dose-escalation study evaluated the pharmacokinetics (PK) of SP-420, a tridentate oral iron chelating agent of the desferrithiocin class, in patients with transfusion dependent β-thalassemia. SP-420 was administered as a single dose of 1.5 (n = 3), 3 (n = 3), 6 (n = 3), 12 (n = 3), and 24 (n = 6) mg/kg or as a twice-daily dose of 9 mg/kg (n = 6) over 14-28 days. There was a near dose-linear increase in the mean plasma SP-420 concentrations and in the mean values for C max and AUC 0-τ over the dose range evaluated. The median t max ranged from 0.5 to 2.25 h and was not dose dependent. The study was prematurely terminated by the sponsor due to renal adverse events (AE) including proteinuria, increase in serum creatinine, and one case of Fanconi syndrome. Other adverse effects included hypersensitivity reactions and gastrointestinal disturbances. Based on current dose administration, the renal AE observed outweighed the possible benefits from chelation therapy. However, additional studies assessing efficacy and safety of lower doses or less frequent dosing of SP-420 over longer durations with close monitoring would be necessary to better explain the findings of our study and characterize the safety of the study drug., (© 2017 Wiley Periodicals, Inc.)

Background: Extracorporeal photopheresis (ECP) culls pathogenic T lymphocytes, be these the clones of cutaneous T-cell lymphoma, or mediators of chronic graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (BMT-GVHD). Whether or not ECP may have an effect in the rarer instances of solid organ transplantation-associated GVHD (SOT-GVHD) is unclear. Mortality rates in SOT-GVHD rival those of transfusion-associated GVHD, with fatalities preceded by pancytopenia and peripheral blood chimerism (PBC) levels exceeding 20%. ECP has been described in two SOT-GVHD cases to date, with one surviving., Study Design and Methods: Clinicolaboratory features (including HLA relationships) in a case of multivisceral transplantation were reviewed from the time of surgery to the onset and progression of SOT-GVHD. ECP, which was introduced as a less immunosuppressive and more selective intervention, was assessed for its effect on serial PBC (as measured by short-tandem-repeat analysis) and clinical outcome., Results: Multivisceral SOT-GVHD manifested with erythroderma, neutropenic sepsis, and PBC increasing from 6% on Posttransplant Day (PTD) 38 to 78% by PTD 60 (at a doubling time of 6 days despite corticosteroids). ECP was administered on PTDs 62 and 67 and was associated with the first evidence of PBC decay to 67% on PTD 69. Death nevertheless ensued on the last day of salvage antithymocyte globulin (PTDs 69-73) despite further PBC reduction to 41%., Conclusion: Further study is needed to determine if the sooner or more frequent application of ECP might attenuate the high case fatality rates of SOT-GVHD., (© 2016 AABB.)

Background: EspP (E. coli secreted serine protease, large plasmid encoded) is an extracellular serine protease produced by enterohemorrhagic E. coli (EHEC) O157:H7, a causative agent of diarrhea-associated Hemolytic Uremic Syndrome (D+HUS). The mechanism by which EHEC induces D+HUS has not been fully elucidated., Objectives: We investigated the effects of EspP on clot formation and lysis in human blood., Methods: Human whole blood and plasma were incubated with EspP(WT )at various concentrations and sampled at various time points. Thrombin time (TT), prothrombin time (PT), and activated partial thromboplastin time (aPTT), coagulation factor activities, and thrombelastgraphy (TEG) were measured., Results and Conclusions: Human whole blood or plasma incubated with EspP(WT) was found to have prolonged PT, aPTT, and TT. Furthermore, human whole blood or plasma incubated with EspP(WT) had reduced activities of coagulation factors V, VII, VIII, and XII, as well as prothrombin. EspP did not alter the activities of coagulation factors IX, X, or XI. When analyzed by whole blood TEG, EspP decreased the maximum amplitude of the clot, and increased the clot lysis. Our results indicate that EspP alters hemostasis in vitro by decreasing the activities of coagulation factors V, VII, VIII, and XII, and of prothrombin, by reducing the clot strength and accelerating fibrinolysis, and provide further evidence of a functional role for this protease in the virulence of EHEC and the development of D+HUS.

Background: Whether the presence of hyperdense artery sign (HAS) correlates with clot characteristics and response to intravenous thrombotic therapy (IVT) remains to be determined. Given that the existent literature was mainly from the Western nations, the current study aimed to examine the relationships among HAS, clot characteristics, and outcome of IVT in a Han Chinese sample in Taiwan. The specific objectives are (1) to correlate HAS with clot characteristics and (2) to explore relationships between HAS and effectiveness/complication of IVT., Methods: We enrolled 75 patients treated with IVT following acute large arterial infarctions. All patients had a baseline brain computed tomography and a follow-up image at 24 hours after thrombolysis. Correlations were explored between HAS and clot characteristics. Multivariable logistic regressions were employed to examine the relationships between HAS and response to IVT at 24 hours, including early improvement and all forms of intracerebral hemorrhage (ICH)., Results: In this Han Chinese sample in Taiwan, 50.7% of the patients had HAS and 64% had early improvements following IVT. Those with HAS tended to have clots lodging at main trunks of cerebral arteries but no significant associations were found between HAS and stroke etiology. In multivariable logistic regressions, HAS predicted neither early improvement nor ICH complication., Conclusions: Instead of clot etiology, we found that it might be clot location that correlated with HAS. HAS was not associated with early improvement or ICH complication after IVT in this Han Chinese sample. We also showed that some other patient characteristics were likely to influence outcomes of IVT, which warrant clinical attention., (Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Carotid-esophageal fistula (CEF) could be a serious complication of esophageal cancer in a patient receiving radiotherapy. We reported a 47-year-old male patient with advanced cervical esophageal cancer under radiotherapy who developed CEF with the presentations of unstable vital signs and disturbances of consciousness. Carotid-esophageal fistula-associated life-threatening conditions of carotid blowout syndrome and cerebral gas embolism were diagnosed after presentation. Subsequently, intramural dissection of esophageal and gastric walls, profound hemoperitoneum, and hypovolemic shock occurred. When a patient who had an underlying cervical esophageal cancer treated by radiotherapy develops unstable vital signs and neurological symptoms, CEF should be kept in mind in the differential diagnoses. Physicians must be alert of the associated complications of carotid blowout syndrome and cerebral gas embolism and perform timely management including decompression, fluid resuscitation, and aggressive endovascular procedure when indicated.

Background: Evidence regarding the relationships between the socioeconomic status and long-term outcomes of individuals with bipolar affective disorder (BPD) is lacking., Aims: We aimed to estimate the effects of baseline socioeconomic status on longitudinal outcomes., Method: A national cohort of adult participants with newly diagnosed BPD was identified in 2008. The effects of personal and household socioeconomic status were explored on outcomes of hospital treatment, mortality and healthcare costs, over a 3-year follow-up period (2008-2011)., Results: A total of 7987 participants were recruited. The relative risks of hospital treatment and mortality were found elevated for the ones from low-income households who also had higher healthcare costs. Low premium levels did not correlate with future healthcare costs., Conclusions: Socioeconomic deprivation is associated with poorer outcome and higher healthcare costs in BPD patients. Special care should be given to those with lower socioeconomic status to improve outcomes with potential benefits of cost savings in the following years., Declaration of Interest: None., Copyright and Usage: © 2016 The Royal College of Psychiatrists. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

Pregnancy in women with sickle cell disease is associated with adverse maternal and neonatal outcomes. Studies assessing the effects of prophylactic red blood cell transfusions on these outcomes have drawn inconsistent conclusions. The objective of this systematic review was to assess the effect of prophylactic compared with on-demand red blood cell transfusions on maternal and neonatal outcomes in women with sickle cell disease. A systematic search of several medical literature databases was conducted. Twelve studies involving 1291 participants met inclusion criteria. The studies had moderate to high risk of bias. Meta-analysis demonstrated that prophylactic transfusion was associated with a reduction in maternal mortality (7 studies, 955 participants; odds ratio [OR], 0.23; 95% confidence interval [CI], 0.06-0.91), vaso-occlusive pain episodes (11 studies, 1219 participants; OR, 0.26; 95% CI, 0.09-0.76), pulmonary complications (9 studies, 1019 participants; OR, 0.25; 95% CI, 0.09-0.72), pulmonary embolism (3 studies, 237 participants; OR, 0.07; 95% CI, 0.01-0.41), pyelonephritis (6 studies, 455 participants; OR, 0.19; 95% CI, 0.07-0.51), perinatal mortality (8 studies, 1140 participants; OR, 0.43; 95% CI, 0.19-0.99), neonatal death (5 studies, 374 participants; OR, 0.26; 95% CI, 0.07-0.93), and preterm birth (9 studies, 1123 participants; OR, 0.59; 95% CI, 0.37-0.96). Event rates for most of the results were low. Prophylactic transfusions may positively impact several adverse maternal and neonatal outcomes in women with sickle cell disease; however, the evidence stems from a relatively small number of studies with methodologic limitations. A prospective, multicenter, randomized trial is needed to determine whether the potential benefits balance the risks of prophylactic transfusions., (© 2015 by The American Society of Hematology.)

Background: Although depression and chronic pain frequently co-occur, there is a lack of clarity in the literature regarding the cost-effectiveness and cost-utility of antidepressants in the presence of these two conditions. From the perspective of healthcare provider, the current study aims to compare the cost-effectiveness and cost-utility of antidepressants in a national cohort of depressed patients with and without comorbid pain conditions., Methods: Adult patients prescribed with antidepressants for depression were identified from the National Health Insurance Research Database in Taiwan (n=96,501). By using remission as effectiveness measure and quality-adjusted life years (QALYs) as utility measure, the cost-effectiveness and cost-utility were compared across selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), and tricyclic antidepressants (TCAs), as well as by the presence of comorbid painful physical symptoms (PPS)., Results: SSRIs dominated SNRIs in both the cost-effectiveness and cost-utility regardless of comorbid PPS. In comparison with TCAs, SSRIs were likely to be the cost-effective option for patients without PPS. In patients with PPS, the cost-utility advantage for SSRIs over TCAs varied with threshold willingness-to-pay levels. Comorbid PPS may be considered an effect modifier of the cost-utility comparisons between SSRIs and TCAs., Conclusions: For depressed patients without PPS, SSRIs are likely to be cost-effective in improving remission rates and QALYs compared to TCAs and SNRIs. However, to improve cost-utility in those with comorbid PPS, people need to choose between SSRIs and TCAs according to threshold willingness-to-pay levels. Future research is warranted to clarify the impacts of different pain conditions on the economic evaluations of pharmacological treatments in patients with depression., (Copyright © 2015 Elsevier Ltd. All rights reserved.)