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Kidney international 101(2), 256-273 (2022). doi:10.1016/j.kint.2021.10.025, Published by Elsevier, New York, NY

BACKGROUND & AIMS: Wilson disease (WD) is a genetic disease with systemic accumulation of copper that leads to symptoms from the liver and brain. However, the underlying defects in copper transport kinetics are only partly understood. We sought to quantify hepatic copper turnover in patients with WD compared with heterozygote and control subjects using positron emission tomography (PET) with copper-64 (64 Cu) as tracer. Furthermore, we assessed the diagnostic potential of the method.METHODS: Nine patients with WD, five healthy heterozygote subjects, and eight healthy controls were injected with an intravenous bolus of 64 Cu followed by a 90-min dynamic PET scan of the liver and static whole-body PET/CT scans after 1.5, 6, and 20 hours. Blood 64 Cu concentrations were measured in parallel. The hepatic copper retention and redistribution were evaluated by standardized uptake values (SUV).RESULTS: At 90 min, the hepatic SUVs were similar in the three groups. In contrast, at 20 hours post injection, the SUV in WD patient (Mean±SEM 31±4) was higher than in heterozygotes (24±3) or controls (21±4), (p < 0.001). An SUV-ratio of the hepatic 64 Cu concentration at 20 and 1.5 hours completely discriminated between the WD patients and control groups (p < 0.0001; ANOVA). By Patlak-analysis of the initial 90 min of the PET scan, the steady-state hepatic clearance of 64 Cu was estimated to be slightly lower in the patients with WD than in controls, (p = 0.04).CONCLUSIONS: 64 Cu PET imaging enables visualisation and quantification of the hepatic copper retention characteristic for WD patients. This method represents a valuable tool for future studies of WD pathophysiology, which may assist the development of novel therapies, and accurate diagnosis.

Purpose The aim of this study was to analyze the impact of minimally invasive intermittent Pringle maneuver (IPM) on postoperative outcomes in patients with hepatocellular carcinoma (HCC) and liver cirrhosis. Methods In this retrospective cohort study, we evaluated the safety of IPM in patients with HCC who underwent minimally invasive liver resection during five years at our center. Factors influencing the use of IPM were examined in univariate and multivariate regression analysis. Cases with use of IPM (IPM) and those without use of IPM (no IPM) were then compared regarding intraoperative and postoperative outcomes after propensity score matching (PSM) for surgical difficulty. Results One hundred fifty-one patients underwent liver resection for HCC at our center and met inclusion criteria. Of these, 73 patients (48%) received IPM with a median duration of 18 min (5–78). One hundred patients (66%) had confirmed liver cirrhosis. In multivariate analysis, patients with large tumors (≥ 3 cm) and difficult tumor locations (segments VII or VIII) were more likely to undergo IPM (OR 1.176, p = 0.043, and OR 3.243, p = 0.001, respectively). After PSM, there were no differences in intraoperative blood transfusion or postoperative complication rates between the IPM and no IPM groups. Neither did we observe any differences in the subgroup analysis for cirrhotic patients. Postoperative serum liver function tests were not affected by the use of IPM. Conclusions Based on our findings, we conclude that the use of IPM in minimally invasive liver resection is safe and feasible for patients with HCC, including those with compensated liver cirrhosis.

Quantum computing systems are developing rapidly as powerful solvers for a variety of real-world calculations. Traditionally, many of these same applications are solved using conventional high-performance computing (HPC) systems, which have progressed sharply through decades of hardware and software improvements. Here, we present a perspective on the motivations and challenges of pairing quantum computing systems with modern HPC infrastructure. We outline considerations and requirements for the use cases, macroarchitecture, microarchitecture, and programming models needed to integrate near-term quantum computers with HPC system, and we conclude with the expectation that such efforts are well within reach of current technology.

Mobile electrocardiogram (mECG) devices are being used increasingly, supplying recordings to providers and providing automatic rhythm interpretation. Given the intermittent nature of certain cardiac arrhythmias, mECGs allow instant access to a recording device. In the current COVID-19 pandemic, efforts to limit in-person patient interactions and avoid overwhelming emergency and inpatient services would add value. Our goal was to evaluate whether a mECG device would reduce healthcare utilization overall, particularly those of urgent nature. We identified a cohort of KardiaMobile (AliveCor, USA) mECG users and compared their healthcare utilization 1 year prior to obtaining the device and 1 year after. One hundred and twenty-eight patients were studied (mean age 64, 47% female). Mean duration of follow-up pre-intervention was 9.8 months. One hundred and twenty-three of 128 individuals completed post-intervention follow-up. Patients were less likely to have cardiac monitors ordered (30 vs 6; p

Aims Proton beam therapy (PBT) has increasingly been applied for the treatment of young children when radiotherapy is needed. The treatment requires intensive multimodality care and is logistically demanding. In this analysis, we evaluated our experiences in treating infants with tumours of the central nervous system with PBT. Materials and methods Children younger than 2 years of age treated with PBT for central nervous system tumours enrolled in the prospective registry study KiProReg were retrospectively analysed. Information on patient characteristics, treatment, toxicities and outcome were evaluated. Adverse events were classified according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE V4.0) before, during and after PBT. Results Between September 2013 and June 2018, 51 infants were eligible. The median age was 19 months (range 11–23 months) at the time of PBT. Tumour entities were ependymoma (51.0%), atypical teratoid rhabdoid tumour (39.0%), high-grade glioma (6.0%), pineoblastoma (2.0%) and medulloblastoma (2.0%). The prescribed median total dose was 54.0 Gy (range 45.0–59.4 Gy). Most received local radiotherapy. In four patients, craniospinal irradiation followed by a boost to the local tumour bed was applied. The median follow-up time was 42.0 months (range 7.3–86.2 months). The estimated 3-year local control, progression-free survival and overall survival rates for all patients were 62.7, 47.1 and 76.5%, respectively. During radiotherapy, 24 events of higher-grade (CTCAE ≥ °III) toxicities were reported. Interruption of radiotherapy for more than 2 days was due to infection (n = 3) or shunt complication (n = 2). Unexpected hospitalisation during radiotherapy affected 12 patients. Late adverse events attributable to radiotherapy included endocrinopathy (CTCAE °II; 7.8%), new onset of hearing loss (CTCAE °III; 5.8%) and visual impairment (CTCAE °IV; 1.9%). Transient radiation-induced imaging changes occurred in five patients (9.8%). Conclusions Our study indicates that PBT is feasible for very young children with central nervous system tumours, at least in the short term. However, it requires challenging interdisciplinary medical care and high logistical effort. For evaluation of late effects, longer follow-up and evaluation of neurocognitive outcome are desirable. More data have to be gathered to further define the role of radiotherapy in infants over time.

Mobile electrocardiographic (mECG) devices that record ECG lead I have been used to detect atrial fibrillation. Other arrhythmias may not be readily diagnosed with one lead. Obtaining multi‑lead tracings from an mECG (MLmECG) to simulate a 12‑lead ECG may lead to more accurate diagnoses.We developed a method to generate multi‑lead ECGs using a mECG device by attaching it with alligator clips connected to an insulated copper wire to adhesive electrodes on the patient's limbs and torso according to standard lead configurations. Different rhythm and conduction abnormalities from a sample of inpatients were collected. Arrhythmias were recorded in three ways (single lead, MLmECG, and standard 12‑lead) and grouped by category. Recordings were sent to cardiology fellows in the form of a multiple choice survey. Participants were asked for their diagnosis and confidence in their decision.Survey response rate was 100%. Single‑lead, MLmECG, and 12‑lead yielded 48.2%, 81.6%, and 88.6% of agreement with the correct diagnosis, respectively (single‑lead vs. MLmECG or 12‑lead; p0.01). Overall mean confidence scores were 3.34, 4.35, and 4.53 out of 5, for single‑lead, MLmECG, and 12‑lead ECG, respectively (single‑lead vs. MLmECG or 12‑lead; p0.01, MLmECG vs. 12‑lead; p = 0.09).The diagnostic accuracy of MLmECGs were similar to that of a standard 12‑lead ECG. Fellows' confidence in their diagnosis were similar between MLmECG or 12‑lead ECG, and higher with both modalities compared to a single‑lead tracing. The ability to recreate, as fully as possible, a standard 12‑lead ECG is a reasonable goal for mobile technology.

This article takes the perspective of the street-level bureaucrat (SLB) as policy entrepreneur, asking when SLBs are more or less likely to engage in actions aimed at policy change. Drawing on an interdisciplinary approach that connects the public management and policy implementation literatures, this article explores the gap between intentions and behavior in street-level policy entrepreneurship. It investigates two individual and organizational variables (coupling self-efficacy and organizational climate for innovation) that mediate and moderate the relationships between attitudes toward policy entrepreneurship, intentions to engage in policy entrepreneurship, and actual entrepreneurial behavior among SLBs. We demonstrate how strengthening the individual and organizational variables discussed can help organizations improve their bottom-up policy making.

A New Oral History Modality?

While minimally invasive liver surgery has been increasingly adopted at least for minor resections, experience with robotic liver surgery is still limited to a few highly specialized centers. Due to the fear of abdominal adhesions, a history of prior surgeries is still used as an argument for open approaches. Clinical data of all consecutive robotic resections at our center, using the da Vinci Xi surgical system, between April, 2018 and December, 2020, were collected and analyzed as part of a prospective, post-marketing observational study (DRKS00017229). Prior abdominal surgeries were specified according to the surgical approach and localization. Baseline and perioperative outcome criteria were compared between patients with prior surgeries (PS) and patients with no prior surgeries (NPS) in univariate and multivariate analyses. Out of the 126 patients undergoing robotic liver resections, 59% had a history of abdominal surgeries, which were most often colorectal resections (28%) followed by liver resections (20%). Patients with NPS were more likely to undergo robotic liver resection for hepatocellular carcinoma or benign tumors, and to have underlying liver cirrhosis when compared to patients with PS. Other baseline characteristics as well as the extent of resections were similar. Duration of surgery (258 min), conversion rates (6%), and postoperative complications rates (21% Clavien–Dindo ≥ 3) showed no differences between NPS and PS. A subgroup of patients with a history of prior liver surgery showed a longer duration of surgery in univariate analysis. However, this was not confirmed in multivariate analysis which instead revealed tumor entity and liver cirrhosis as independently correlated with duration of surgery. We propose robotic liver resection to be safe and feasible, including in patients with prior abdominal surgeries. Each patient should be evaluated for a minimally invasive procedure regardless of a history of previous operations.

To characterize postoperative pain after tympanoplasty and tympanomastoidectomy and correlate between pain severity and various technical aspects of the surgery. We carried out a prospective cohort study of patients undergoing ear surgery in a tertiary referral center between 7/2018 and 7/2019. Patients filled in a pain questionnaire and scored pain intensity on a visual analog scale preoperatively and on postoperative days (POD) 1–4, 21, and 49. The responses were correlated with clinical and operative data, including surgical technique-related details. Sixty-two patients participated in the study (27 males and 35 females, average age 41.1 ± 20.02 years [range 18–68]). The median preoperative VAS was 5, followed by 6 on POD1, 5 on POD3, and 1 at 3 and 9 weeks. The preoperative questionnaire score normalized to 10 was 4.5 (32/70), 5.1 on POD1, 4.7 on POD3, 0.85 at 3 weeks and 0.85 at 9 weeks. The predictive factors for increased postoperative pain were younger age, the presence of a comorbidity, revision surgery, preoperative dizziness or tinnitus and postoperative tinnitus. The predictive factors for decreased pain were smoking and the addition of a mastoidectomy. None of the factors related to the surgical technique (e.g., surgical approaches, type of reconstruction, specific surgeon) significantly affected the questionnaire responses or the pain VAS intensity scores. We demonstrated that younger age, the presence of a comorbidity, revision surgery, preoperative dizziness or tinnitus and postoperative tinnitus were predictors of increased pain after tympanoplasty and tympanomastoidectomy, while the inclusion of a mastoidectomy was a predictor of decreased pain.

BACKGROUND Effective concepts are required to overcome the negative impact of daily stressful overwhelming. We investigated the effectiveness of a 1-week multimodal program for stress reduction. METHODS We performed a randomized controlled trial including adults with above-average stress level. The intervention consisted of health coaching, relaxation, physical activity, and balneotherapeutic elements. Individuals were randomized either to the intervention group (IG) or to one of the two control groups B and C. The main outcome was change in stress (Perceived Stress Questionnaire PSQ, Screening Scale of Chronic Stress of the Trier Inventory for Chronic Stress TICS-SSCS) at 6 months post intervention; further outcomes were well-being (World Health Organization 5-Item Well-Being Index WHO-5) and health status (EuroQol visual analog scale EQ-5D VAS). Data were collected pre/post intervention as well as after 1, 3, and 6 months. RESULTS Data of 96 individuals (mean age 48.0 years, 74{\%} female) were available for analyses. The IG improved overtime with -13.45 points for the PSQ and -6.44 points for the TICS-SSCS after 6 months. At 6-month follow-up the IG did not significantly differ from group B (PSQ: p = 0.2332; TICS-SSCS: p = 0.0805) or group C (PSQ: p = 0.0950; TICS-SSCS: p = 0.0607) when controlling for baseline (ANCOVA). Compared to group C, ANCOVA revealed significant differences in WHO-5 (p = 0.0292) and EQ-5D VAS (p = 0.0177) post intervention. At the 3- and 6-month follow-up and compared to group B, no substantial differences could be found for WHO-5 and EQ-5D VAS. CONCLUSION The results indicate that even a short-term multimodal program for stress reduction appears to set a positive trend towards less perceived and chronic stress. Hintergrund: Es bedarf effektiver Ans{\"a}tze, um den negativen Einfl{\"u}ssen t{\"a}glicher stressreicher Belastungen zu begegnen. Wir untersuchten die Wirksamkeit eines einw{\"o}chigen multimodalen Programms zur Stressreduzie­rung. Methoden: Wir f{\"u}hrten eine randomisierte kontrollierte Studie mit Erwachsenen durch, die ein erh{\"o}htes Stresslevel aufwiesen. Die Intervention beinhaltete ein Gesundheitscoaching, Entspannungs- und Bewegungs­einheiten sowie balneotherapeutische Elemente. Die Teilnehmenden wurden entweder in die Interventionsgruppe (IG) oder in eine von zwei Kontrollgruppen B oder C randomisiert. Die prim{\"a}re Zielgr{\"o}{\ss}e war die Ver{\"a}nde­rung im Stressniveau (Perceived Stress Questionnaire PSQ, Screening Scale of Chronic Stress of the Trier Inventory for Chronic Stress TICS-SSCS) 6 Monate nach der Intervention; weitere Zielgr{\"o}{\ss}en waren das Wohlbefinden (World Health Organization 5-Item Well-Being Index WHO-5) und der aktuelle Gesundheitsstatus (EuroQol visuelle Analogskala EQ-5D VAS). Daten wurden vor und nach der Intervention erfasst sowie nach 1, 3 und 6 Mona­ten. Ergebnisse: Daten von 96 Teilnehmenden (mittleres Alter 48.0 Jahre, 74{\%} weiblich) standen f{\"u}r die Analyse zur Verf{\"u}gung. Die IG verbesserte sich im Zeitverlauf, mit --13.45 Punkten im PSQ sowie --6.44 Punkten im TICS-SSCS nach 6 Monaten. Zum 6-Monats-Follow-up unterschied sich die IG nicht signifikant von Gruppe B (PSQ: p = 0.2332; TICS-SSCS: p = 0.0805) oder Gruppe C (PSQ: p = 0.0950; TICS-SSCS: p = 0.0607), kontrolliert f{\"u}r den Ausgangswert (ANCOVA). Verglichen mit Gruppe C zeigte die ANCOVA nach der Intervention signifikante Unterschiede im WHO-5 (p = 0.0292) und der EQ-5D VAS (p = 0.0177). Zum 3- und 6-Monats-Follow-up sowie verglichen mit Gruppe B konnten keine substanziellen Unterschiede im WHO-5 und der EQ-5D VAS gefunden werden. Schlussfolgerung: Die Ergebnisse weisen darauf hin, dass selbst ein kurzes multimodales Programm zur Stressreduzierung einen positiven Trend hin zu weniger subjektiv wahrgenommenem und chronischem Stress setzen kann.

Introduction:The year 2020 was defined by the 29,903 base pairs of RNA that codes for the SARS-CoV-2 genome. SARS-CoV-2 infects humans to cause COVID-19, spreading from patient-to-patient yet impacts patients very divergently. Areas covered: Within this review, we address the known molecular mechanisms and supporting data for COVID-19 clinical course and pathology, clinical risk factors and molecular signatures, therapeutics of severe COVID-19, and reinfection/vaccination. Literature and published datasets were reviewed using PubMed, Google Scholar, and NCBI SRA tools. The combination of exaggerated cytokine signaling, pneumonia, NETosis, pyroptosis, thrombocytopathy, endotheliopathy, multiple organ dysfunction syndrome (MODS), and acute respiratory distress syndrome (ARDS) create a positive feedback loop of severe damage in patients with COVID-19 that impacts the entire body and may persist for months following infection. Understanding the molecular pathways of severe COVID-19 opens the door for novel therapeutic design. We summarize the current insights into pathology, risk factors, secondary infections, genetics, omics, and drugs being tested to treat severe COVID-19. Expert opinion: A growing level of support suggests the need for stronger integration of biomarkers and precision medicine to guide treatment strategies of severe COVID-19, where each patient has unique outcomes and thus require guided treatment.

Multiple sclerosis (MS), which is a chronic inflammatory disease of the central nervous system, still represents one of the most common causes of persisting disability with an early disease onset. Growing evidence suggests B cells to play a crucial role in its pathogenesis and progression. Over the last decades, monoclonal antibodies (mabs) against the surface protein CD20 have been intensively studied as a B cell targeting therapy in relapsing MS (RMS) as well as primary progressive MS (PPMS). Pivotal studies on anti-CD20 therapy in RMS showed remarkable clinical and radiological effects, especially on acute inflammation and relapse biology. These results paved the way for further research on the implication of B cells in the pathogenesis of MS. Besides controlling relapse development in RMS, ocrelizumab (OCR) also showed clinical benefits in patients with PPMS and became the first approved drug for this disease course. In this review, we provide an overview of the current anti-CD20 mabs used or tested for the treatment of MS—namely rituximab (RTX), OCR, ofatumumab (OFA), and ublituximab (UB). Besides their effectiveness, we also discuss possible limitations and safety concerns especially in regard to long-term treatment, both for this class of drugs overall as well as for each anti-CD20 mab individually. Additionally, we elucidate to what extent anti-CD20 therapy may alter the function of other immune cells, both directly or indirectly. Finally, we cover the current knowledge on repopulation of CD20+ cells after cessation of anti-CD20 treatment and discuss future aspirations towards alternative, further developed B cell silencing therapies. Supplementary Information The online version contains supplementary material available at 10.1007/s13311-021-01048-z.

Background Recent clinical advances in cancer immuno-therapeutics underscore the need for improved understanding of the complex relationship between cancer and the multiple, multi-functional, inter-dependent, cellular and humoral mediators/regulators of the human immune system. This interdisciplinary effort exploits engineering analysis methods utilized to investigate anomalous physical system behaviors to explore immune system behaviors. Cancer Immune Control Dynamics (CICD), a systems analysis approach, attempts to identify differences between systemic immune homeostasis of 27 healthy volunteers versus 14 patients with metastatic malignant melanoma based on daily serial measurements of conventional peripheral blood biomarkers (15 cell subsets, 35 cytokines). The modeling strategy applies engineering control theory to analyze an individual’s immune system based on the biomarkers’ dynamic non-linear oscillatory behaviors. The reverse engineering analysis uses a Singular Value Decomposition (SVD) algorithm to solve the inverse problem and identify a solution profile of the active biomarker relationships. Herein, 28,605 biologically possible biomarker interactions are modeled by a set of matrix equations creating a system interaction model. CICD quantifies the model with a participant’s biomarker data then computationally solves it to measure each relationship’s activity allowing a visualization of the individual’s current state of immunity. Results CICD results provide initial evidence that this model-based analysis is consistent with identified roles of biomarkers in systemic immunity of cancer patients versus that of healthy volunteers. The mathematical computations alone identified a plausible network of immune cells, including T cells, natural killer (NK) cells, monocytes, and dendritic cells (DC) with cytokines MCP-1 [CXCL2], IP-10 [CXCL10], and IL-8 that play a role in sustaining the state of immunity in advanced cancer. Conclusions With CICD modeling capabilities, the complexity of the immune system is mathematically quantified through thousands of possible interactions between multiple biomarkers. Therefore, the overall state of an individual’s immune system regardless of clinical status, is modeled as reflected in their blood samples. It is anticipated that CICD-based capabilities will provide tools to specifically address cancer and treatment modulated (immune checkpoint inhibitors) parameters of human immunity, revealing clinically relevant biological interactions.

Study Design: Retrospective chart review.Purpose: This study compared the clinical and radiographic outcomes of patients treated with expandable and static interbody spacers following minimally invasive lateral lumbar interbody fusion (MIS-LLIF) with 12-month follow-up.Overview of Literature: A common surgical option for the treatment of degenerative disk disease (DDD) is MIS-LLIF using static or expandable spacers to restore disk height (DH), neuroforaminal height (NH), and segmental lordosis. Static spacers may require excessive trialing and aggressive impaction, potentially leading to endplate disruption and subsidence. Expandable spacers allow for in situ expansion to help address complications associated with static spacers.Methods: This is an Institutional Review Board-exempt review of 69 patients (static, n=32; expandable, n=37) diagnosed with DDD who underwent MIS-LLIF at 1–2 contiguous level(s) using static or expandable spacers. Radiographic and clinical outcomes were collected and compared at pre- and postoperative time points up to 12 months.Results: The expandable group had a significantly higher mean change in Visual Analog Scale (VAS) scores at 6 weeks, 6 months, and 12 months vs. static (∆VAS at 12 months: expandable, 6.7±1.3; static, 5.1±2.6). Mean improvement of Oswestry Disability Index (ODI) scores at 3, 6, and 12 months were significantly better for the expandable group vs. static (∆ODI at 12 months: expandable, 63.2±13.2; static, 29.8±23.4). Mean DH and NH significantly increased at final follow-up for both groups, with no significant difference in DH improvement between groups. The expandable mean NH improvement at 6 weeks and 6 months was significantly greater vs. static. Segmental lordosis significantly improved in the expandable group at all time intervals vs static. Subsidence rate at 12 months was significantly lower in the expandable group (1/46, 2.2%) vs. static (12/37, 32.4%).Conclusions: Expandable spacers resulted in a significantly lower subsidence rate, improve segmental lordosis, and VAS and ODI outcomes at 12 months vs. static.

Simulations highlight the potential of genomic selection to substantially increase genetic gain for complex traits in sugarcane. The success rate depends on the trait genetic architecture and the implementation strategy. Genomic selection (GS) has the potential to increase the rate of genetic gain in sugarcane beyond the levels achieved by conventional phenotypic selection (PS). To assess different implementation strategies, we simulated two different GS-based breeding strategies and compared genetic gain and genetic variance over five breeding cycles to standard PS. GS scheme 1 followed similar routines like conventional PS but included three rapid recurrent genomic selection (RRGS) steps. GS scheme 2 also included three RRGS steps but did not include a progeny assessment stage and therefore differed more fundamentally from PS. Under an additive trait model, both simulated GS schemes achieved annual genetic gains of 2.6-2.7% which were 1.9 times higher compared to standard phenotypic selection (1.4%). For a complex non-additive trait model, the expected annual rates of genetic gain were lower for all breeding schemes; however, the rates for the GS schemes (1.5-1.6%) were still greater than PS (1.1%). Investigating cost-benefit ratios with regard to numbers of genotyped clones showed that substantial benefits could be achieved when only 1500 clones were genotyped per 10-year breeding cycle for the additive genetic model. Our results show that under a complex non-additive genetic model, the success rate of GS depends on the implementation strategy, the number of genotyped clones and the stage of the breeding program, likely reflecting how changes in QTL allele frequencies change additive genetic variance and therefore the efficiency of selection. These results are encouraging and motivate further work to facilitate the adoption of GS in sugarcane breeding.

Background A growing body of evidence supports the safety of the human papillomavirus (HPV) vaccines. However, concerns about autonomic dysfunction syndromes and non-specific symptoms continue to linger. These conditions are not easily captured by traditional diagnostic classification schemes and call for innovative approaches to the study of vaccine safety which take more general measures of all-cause morbidity into account. Methods Taking advantage of the unique Danish registers, including regional registration of absence from school, we conducted a cohort study of 14 068 adolescent Danish girls attending 5th through 9th grade in public schools in the municipality of Copenhagen during 1 August 2013–23 January 2018. We obtained time-varying HPV vaccination status and demographic information from nationwide registers. Using Poisson regression with random effects, we estimated rate ratios (RRs) of absence due to illness, comparing HPV-vaccinated girls with unvaccinated girls with adjustment for grade, season, calendar period, demographic factors and random effects at the individual, class and school levels. Results Our study included 6 206 188 school days with 213 221 days of absence from school due to illness (absence rate, 3.4%). Comparing absence rates due to illness in HPV-vaccinated and unvaccinated girls yielded an adjusted RR of 1.00 (95% confidence interval [CI], 0.98–1.03). Conclusions Our study provides an important and novel contribution to HPV vaccine safety. Using absence from school records, we were able to address important safety concerns without relying on medical diagnoses. We conclude that HPV vaccination does not increase the risk of morbidity in any manner that manifests as absence from school due to illness.

OBJECTIVES: The curative effect of allogeneic haematopoietic stem cell transplantation (HSCT) for acute leukaemia is due in part to the donor T cell-mediated graft-versus-leukaemia immune reaction (GvL). Several studies have suggested that donor CD25+CD4+Foxp3+ regulator T cells (Tregs) may decrease graft-versus-host disease (GvHD) without abrogating GVL. This notion may need modification in acute lymphoblastic leukaemia (ALL).METHODS: Foxp3 mRNA level was measured by qPCR in pre-harvest donor blood CD4+ T cells. The study comprised 45 patients with ALL in 1st or 2nd CR who received myeloablative HSCT using T-replete bone marrow grafts.RESULTS: Relapse occurred in 17 patients median 363 days after HSCT. The relapse risk was estimated by Cox univariate and multivariate proportional hazard regression. The proportionality assumption was met by analysing the pre-harvest donor Foxp3 mRNA level as a time-dependent covariate. Early relapse was not modified by the Foxp3 mRNA level. However, a higher Foxp3 mRNA level was associated with a significantly increased relapse risk after day 363 after transplantation, compatible with inhibition of GvL. In contrast, a higher pre-harvest donor CD4+ T cell concentration was associated with reduced relapse risk.CONCLUSION: A higher pre-harvest donor Foxp3 mRNA level may be predictive of late ALL relapse after HSCT.

We present a modularly applicable, red-shifted and self-reporting photodynamic covalent crosslinker, abbreviated qStyPy, that performs [2+2] cycloadditions upon irradiation with 470 nm in water. The rational design of qStyPy increases its hydrophilicity due to a permanent charge and features a broad emission in the far-red/near-infrared regime as a readout for the cycloadduct formation, rendering qStyPy suitable for biomedical applications.

Background & Aims: Obeticholic acid (OCA) is an agonist of the nuclear bile acid receptor farnesoid X receptor, which regulates hepatic bile acid metabolism. We tested whether OCA treatment would influence hepatic transport of conjugated bile acids in patients with primary biliary cholangitis (PBC) who responded inadequately to treatment with ursodeoxycholic acid (UDCA). Methods: Eight UDCA-treated patients with PBC with alkaline phosphatase ≥1.5 times the upper limit of normal range participated in a double-blind, placebo-controlled study. While continuing on UDCA, the patients were randomised to two 3-month crossover treatment periods with placebo and OCA, in random order, separated by a 1-month washout period without study treatment. After each of the two treatment periods, we determined rate constants for transport of conjugated bile acids between blood, hepatocytes, biliary canaliculi, and bile ducts by positron emission tomography of the liver using the conjugated bile acid tracer [N-methyl- 11C]cholylsarcosine ( 11C-CSar). The hepatic blood perfusion was measured using infusion of indocyanine green and Fick's principle. Results: Compared with placebo, OCA increased hepatic blood perfusion by a median of 11% (p = 0.045), the unidirectional uptake clearance of 11C-CSar from blood into hepatocytes by a median of 11% (p = 0.01), and the rate constant for secretion of 11C-CSar from hepatocytes into biliary canaliculi by a median of 73% (p = 0.03). This resulted in an OCA-induced decrease in the hepatocyte residence time of 11C-CSar by a median of 30% (p = 0.01), from group median 11 min to 8 min. Conclusions: This study of UDCA-treated patients with PBC showed that, compared with placebo, OCA increased the hepatic transport of the conjugated bile acid tracer 11C-CSar, and thus endogenous conjugated bile acids, from hepatocytes into biliary canaliculi. As a result, OCA reduced the time hepatocytes are exposed to potentially cytotoxic bile acids. Lay summary: Primary biliary cholangitis is a chronic liver disease in which the small bile ducts are progressively destroyed. We tested whether the treatment with obeticholic acid (OCA) would improve liver excretion of bile acids compared with placebo in 8 patients with primary biliary cholangitis. A special scanning technique (PET scan) showed that OCA increased the transport of bile acids from blood to bile. OCA thereby reduced the time that potentially toxic bile acids reside in the liver by approximately one-third.

Background: Previous studies suggest a 3- to-10-fold increased risk of multiple sclerosis (MS) in offspring of mothers with diabetes mellitus (DM). Objectives: To examine MS risk in offspring of diabetic mothers, overall and according to type of maternal DM, that is, pregestational DM or gestational DM, as well as to examine MS risk among offspring of diabetic fathers. Methods: The study cohort included all 1,633,436 singletons born in Denmark between 1978 and 2008. MS diagnoses were identified in the Danish Multiple Sclerosis Registry, and parental DM diagnoses in the National Patient Register. We used Cox proportional hazards regression analyses to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for the association of parental DM with MS risk in the offspring. Results: MS risk among individuals whose mothers had pregestational DM was 2.3-fold increased compared with that among individuals with nondiabetic mothers (HR = 2.25; 95% CI: 1.35–3.75, n = 15). MS risk was statistically non-significant among offspring of mothers with gestational DM (HR = 1.03 (95% CI: 0.49–2.16), n = 7) and among offspring of diabetic fathers (HR = 1.40 (95% CI: 0.78–2.54), n = 11). Conclusion: Our nationwide cohort study utilizing high-quality register data in Denmark over several decades corroborates the view that offspring of diabetic mothers may be at an elevated risk of developing MS.

Tourists' role in place valorisation processes is increasingly recognised. Not only do tourists play an important role in adding or subtracting value to places of attractions through their presence...

BACKGROUND Prior knee surgery before total knee arthroplasty (TKA) puts patients at higher risk of inferior outcomes and increased care cost. This study compares intraoperative and postoperative variables including procedure duration, components, length of stay, readmission, complications, and reoperations among patients undergoing conversion TKA. METHODS Primary TKA from a single-surgeon database identified 130 patients with prior knee surgery to form a "conversion" cohort. One-to-one matching identified 130 patients of similar age, American Society of Anesthesiologists score, body mass index, and gender without prior knee surgery for comparison. Perioperative and 90-day postoperative variables were compared between patients with and without prior surgery, within the conversion group based on the type of prior surgery, and whether the prior surgery was bony or soft tissue. RESULTS The conversion group had longer mean operative time (96.1 vs 90.0 minutes, P = .01), higher revision component utilization (8.5% vs 0.8%, P = .005), and higher calculated blood loss (1440 vs 1249 mL, P = .004). Thirty-eight patients with prior fracture or osteotomy were compared to the remaining 92 patients in the conversion group and showed longer operative time (107.1 vs 91.3 minutes, P < .001), higher 90-day readmissions (18.4% vs 3.3%, P = .003), more complications (23.7% vs 8.7%, P = .021), and greater utilization of revision components (26.3% vs 1.1%, P < .001). CONCLUSION Patients undergoing conversion TKA required increased resource utilization, particularly patients with a prior osteotomy or fracture. Policymakers should consider these variables, as they did in conversion THA, in adding a code to account for increased case complexity and resource utilization.

Whether male circumcision in infancy or childhood provides protection against the acquisition of human immunodeficiency virus (HIV) or other sexually transmitted infections (STIs) in adulthood remains to be established. In the first national cohort study to address this issue, we identified 810,719 non-Muslim males born in Denmark between 1977 and 2003 and followed them over the age span 0–36 years between 1977 and 2013. We obtained information about cohort members’ non-therapeutic circumcisions, HIV diagnoses and other STI outcomes from national health registers and used Cox proportional hazards regression analyses to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) associated with foreskin status (i.e., circumcised v. genitally intact). During a mean of 22 years of follow-up, amounting to a total observation period of 17.7 million person-years, 3375 cohort members (0.42%) underwent non-therapeutic circumcision, and 8531 (1.05%) received hospital care for HIV or other STIs. Compared with genitally intact males, rates among circumcised males were not statistically significantly reduced for any specific STI. Indeed, circumcised males had a 53% higher rate of STIs overall (HR = 1.53, 95% CI: 1.24–1.89), and rates were statistically significantly increased for anogenital warts (74 cases in circumcised males v. 7151 cases in intact males, HR = 1.51; 95% CI: 1.20–1.90) and syphilis (four cases in circumcised males v. 197 cases in intact males, HR = 3.32; 95% CI: 1.23–8.95). In this national cohort study spanning more than three decades of observation, non-therapeutic circumcision in infancy or childhood did not appear to provide protection against HIV or other STIs in males up to the age of 36 years. Rather, non-therapeutic circumcision was associated with higher STI rates overall, particularly for anogenital warts and syphilis.

Acute stress may impair cognitive performance and multitasking, both vital in the practice of emergency medicine (EM). Previous research has demonstrated that board-certified emergency physicians experience physiologic stress while working clinically. We sought to determine whether EM residents have a similar stress response, and hypothesized that residents experience acute stress while working clinically.We performed a prospective observational study of physiologic stress including heart rate (HR), heart rate variability (HRV), and subjective stress in EM residents during clinical shifts in the emergency department. HR and HRV were measured via 3-lead Holter monitors and compared to baseline data obtained during weekly educational didactics. Subjective stress was assessed before and after clinical shifts via a Likert-scale questionnaire and written comments.We enrolled 21 residents and acquired data from 40 shifts. Residents experienced an increase in mean HR of eight beats per minute (P0.001) and decrease in HRV of 53.9 milliseconds (P = 0.005) while working clinically. Subjective stress increased during clinical work (P0.001). HRV was negatively correlated with subjective stress, but this did not reach statistical significance (P = 0.09).EM residents experience acute subjective and physiologic stress while working clinically. HR, HRV, and self-reported stress are feasible indicators to assess the acute stress response during residency training. These findings should be studied in a larger, more diverse cohort of residents and efforts made to identify characteristics that contribute to acute stress and to elicit targeted educational interventions to mitigate the acute stress response.

In a large, system-wide, healthcare personnel (HCP) testing experience using severe acute respiratory coronavirus virus 2 (SARS-CoV-2) polymerase chain reaction (PCR) and serologic testing early in the coronavirus disease 2019 (COVID-19) pandemic, we did not find increased infection risk related to COVID-19 patient contact. Our findings support workplace policies for HCP protection and underscore the role of community exposure and asymptomatic infection.

Radiofrequency catheter ablation is a safe and effective treatment option for atrioventricular nodal reentrant tachycardia (AVNRT). A nonirrigated ablation catheter used in a temperature-controlled mode is traditionally used for AVNRT ablation due to the shallow lesion depth required for successful slow-pathway ablation. In this case, a nonirrigated ablation catheter established inadequate lesions to ablate the slow pathway successfully. The adoption of an irrigated contact-force ablation catheter used in a power-controlled mode was necessary to provide higher power and possibly create a deeper lesion to ablate the slow pathway successfully, thus eliminating AVNRT inducibility in this patient.

Background: Visual impairment, specifically anterior segment pathology, presents a significant burden of disease in the world. Introduction: Inexpensive tools are necessary to improve eye health of residents in developing countries where care is difficult to access. Our study aimed at determining whether a $5 macro lens attached to a smartphone camera is an effective anterior segment imaging method for screening diseases. Materials and Methods: Fifty four (n = 54) patients had anterior segment imaging performed by using an Easy Macro lens and an iPhone. Imaging was performed at the Floating Doctors' mobile clinic sites in Panama. Images were sent back and graded by two board-certified ophthalmologists using a modified version of the FOTO-ED scale. Statistical analysis was performed by using a Wilcoxon signed-rank test to compare grades between the two imaging modalities. Results: There was no significant difference in overall clinical utility of images obtained by the iPhone versus Easy Macro lens. The iPhone was significantly superior in imaging of the lens and conjunctiva, whereas the Easy Macro lens was superior in regards to the anterior chamber, iris, and lens. Discussion: The imaging modality that best captures pathology is dependent on what part of the anterior segment is being examined. An imaging protocol with a pair of images, one from a smartphone and one from a macro lens, would have significant clinical utility. Conclusion: Our study demonstrates how minimally trained users can deliver effective eye screening via a telemedicine-based approach in a resource-deprived setting. Future directions would be to develop a telemedicine protocol and determine whether it improves clinically measurable outcomes in patients.

Approaches that root national climate strategies in local actions will be essential for all countries as they develop new nationally determined contributions under the Paris Agreement. The potential impact of climate action from non-national actors in delivering higher global ambition is significant. Sub-national action in the United States provides a test for how such actions can accelerate emissions reductions. We aggregated U.S. state, city, and business commitments within an integrated assessment model to assess how a national climate strategy can be built upon non-state actions. We find that existing commitments alone could reduce emissions 25% below 2005 levels by 2030, and that enhancing actions by these actors could reduce emissions up to 37%. We show how these actions can provide a stepped-up basis for additional federal action to reduce emissions by 49%—consistent with 1.5 °C. Our analysis demonstrates sub-national actions can lead to substantial reductions and support increased national action., Climate action from local actors is vital in achieving nationally determined contributions under the Paris Agreement. Here the authors show that existing commitments from U.S. states, cities and business could reduce emissions 25% below 2005 levels by 2030, with expanded subnational action reducing emissions by 37% and federal action by up to 49%.

ObjectiveOur objective was to estimate the relative risk of IBD among first-generation and second-generation immigrants in Denmark compared with native Danes.DesignUsing national registries, we established a cohort of Danish residents between 1977 and 2018. Cohort members with known country of birth were followed for Crohn’s disease (CD) and ulcerative colitis (UC) diagnoses. Incidence rate ratios (IRRs) served as measures of relative risk and were calculated by log-linear Poisson regression, using rates among native Danes as reference, stratified by IBD risk in parental country of birth, and among first-generation immigrants by age at immigration and duration of stay in Denmark.ResultsAmong 8.7 million Danes, 4156 first-generation and 898 second-generation immigrants were diagnosed with CD or UC. Overall, comparing first-generation immigrants with native Danes, the IRR was 0.80 (95% CI 0.76 to 0.84) for CD and 0.74 (95% CI 0.71 to 0.77) for UC. The IRR of IBD increased with ≥20 years stay in Denmark. The IRR of CD increased with immigration at ≥40 years of age. Comparing second-generation immigrants with native Danes, the IRR of IBD was 0.97 (95% CI 0.91 to 1.04). There was significant interaction with sex, with higher IRR of IBD in male than in female immigrants.ConclusionRelative to native Danish men and women, IBD risk among first-generation immigrants was lower, reflected the risk in their parental country of birth and increased with ≥20 years stay in Denmark. For second-generation immigrants, relative risk of IBD was lower only among women. These complex patterns suggest the role of environmental IBD risk factors.

ObjectiveThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic challenges national health systems and the global economy. Monitoring of infection rates and seroprevalence can guide public health measures to combat the pandemic. This depends on reliable tests on active and former infections. Here, we set out to develop and validate a specific and sensitive enzyme linked immunosorbent assay (ELISA) for detection of anti-SARS-CoV-2 antibody levels.MethodsIn our ELISA, we used SARS-CoV-2 receptor-binding domain (RBD) and a stabilized version of the spike (S) ectodomain as antigens. We assessed sera from patients infected with seasonal coronaviruses, SARS-CoV-2 and controls. We determined and monitored IgM-, IgA- and IgG-antibody responses towards these antigens. In addition, for a panel of 22 sera, virus neutralization and ELISA parameters were measured and correlated.ResultsThe RBD-based ELISA detected SARS-CoV-2-directed antibodies, did not cross-react with seasonal coronavirus antibodies and correlated with virus neutralization (R2 = 0.89). Seroconversion started at 5 days after symptom onset and led to robust antibody levels at 10 days after symptom onset. We demonstrate high specificity (99.3%;N = 1000) and sensitivity (92% for IgA, 96% for IgG and 98% for IgM; > 10 days after PCR-proven infection;N = 53) in serum.ConclusionsWith the described RBD-based ELISA protocol, we provide a reliable test for seroepidemiological surveys. Due to high specificity and strong correlation with virus neutralization, the RBD ELISA holds great potential to become a preferred tool to assess thresholds of protective immunity after infection and vaccination.

Background: Reusable elastomeric respirator use in health care may represent one solution to address N95 respirator shortages experienced during infectious disease outbreaks, but cleaning and disinfection requirements may limit their utility. Evidence of respirator cleaning and disinfection behaviors and practices by health care workers may inform guidance on reusable respirator use. Methods: Medical system elastomeric respirator users were surveyed about respirator cleaning and disinfection practices and perceptions via an electronic survey. Respondents were subsequently classified based on reported compliance with their assigned respirator use. To explore whether respirator cleaning and disinfection issues affected compliance with assigned device use, responses were compared between user groups and adjusted for covariates. Results: A total of 432 of 2,024 (21%) eligible elastomeric respirator users completed the survey. Most (>90%) reported that their respirator was clean, but only 52% reported that they always disinfect their respirators after use according to the hospital’s expected practice. Only 40 respondents (9%) reported regularly cleaning the respirator with soap and water, in accordance with manufacturer recommendations. Reporting of suboptimal decontamination practice was not associated with assigned device compliance, however, except among providers and respiratory therapists. Conclusion/Application to Practice: Although perceptions of cleanliness and adherence to expected decontamination practices during routine use did not appear to influence compliance with assigned respirator use overall, this did predict compliance among providers and respiratory therapists, both of whom have nonfixed workstations. Practical and effective strategies to assure easy access to and availability of clean reusable respiratory protective devices are needed to facilitate their use in health care respiratory protection programs.

Objective This study evaluated the risk of subclinical atrial fibrillation (AF) in patients with central retinal artery occlusion (CRAO) compared to those with cryptogenic stroke using implantable loop recorders (ILR). Methods We conducted a retrospective analysis of 273 consecutive patients who had ILRs inserted at our institution for either cryptogenic stroke (n = 227) or CRAO (n = 46). Our primary endpoint was a time to event analysis for the new diagnosis of AF by ILR. Univariable and multivariable Cox proportional hazard models were used to determine the predictors of time-to-AF. Results A total of 64 patients were found to have newly diagnosed AF by remote monitoring of the ILR. AF was detected in 57 of 227 (25%) cryptogenic stroke patients by the end of a maximum 5.1 years follow-up and in 7 of 46 (15%) CRAO patients by the end of a maximum 3.6year follow-up (p = .215, log-rank test). The Kaplan-Meier estimates for freedom from AF was 59.4% for CRAO and 66.6% for cryptogenic stroke (p = NS, log-rank test). Baseline variables predicting AF included older patients, higher CHADS2 VASC score, longer PR interval on initial EKG evaluation and mitral annular calcification (MAC) on transthoracic echocardiogram. Conclusions Patients with CRAO are at risk for subclinical AF, similar to those with cryptogenic stroke. Long term monitoring to detect AF may lead to changes in pharmacotherapy to reduce the risk for subsequent stroke. This article is protected by copyright. All rights reserved.

Prompt identification of acute coronary syndrome is a challenge in clinical practice. The 12-lead electrocardiogram (ECG) is readily available during initial patient evaluation, but current rule-based interpretation approaches lack sufficient accuracy. Here we report machine learning-based methods for the prediction of underlying acute myocardial ischemia in patients with chest pain. Using 554 temporal-spatial features of the 12-lead ECG, we train and test multiple classifiers on two independent prospective patient cohorts (n = 1244). While maintaining higher negative predictive value, our final fusion model achieves 52% gain in sensitivity compared to commercial interpretation software and 37% gain in sensitivity compared to experienced clinicians. Such an ultra-early, ECG-based clinical decision support tool, when combined with the judgment of trained emergency personnel, would help to improve clinical outcomes and reduce unnecessary costs in patients with chest pain., Diagnosing a heart attack requires excessive testing and prolonged observation, which frequently requires hospital admission. Here the authors report a machine learning-based system based exclusively on ECG data that can help clinicians identify 37% more heart attacks during initial screening.

ObjectiveA significant decrease in aneurysm related survival is observed at long term follow up after infrarenal endovascular aneurysm repair (EVAR) compared with open repair. Therefore, longer term results with new generation endografts are essential. The aim of this post-approval French multicentre prospective observational study (EPI-ANA-01) was to evaluate the technical success and five year mortality and secondary intervention rates of the third generation AnacondaTM endograft.MethodsFrom June 2012 to October 2013, 176 consecutive unruptured infrarenal abdominal aortic aneurysms were included (160 male patients, mean age 75.3 ± 8.4 years). Survival, freedom from type Ia endoleak, limb events, and re-interventions were estimated using the Kaplan–Meier method. Anatomical and clinical characteristics were compared according to the occurrence of migration, conversion, adverse limb events, endoleak, and sac enlargement.ResultsThe primary technical and clinical success rates were 98.3% and 94.9%, respectively. A hostile neck was identified in 33.9% of patients and 10.7% were treated outside instructions for use (IFU). An early post-operative (≤30 days) mortality rate of 1.7% was observed. At one and five years, respectively, the overall survival rate was 94.9% and 65.9% (aneurysm related in four patients [2.3%]) and the clinical success rate was 90.9% and 70.6%. Secondary interventions were performed in 35 of 176 patients (19.9%). The overall limb occlusion rate was 7.9% and the aneurysm sac diameter decreased significantly (pre-operative diameter 53.9 ± 8.6 mm vs. 42.3 ± 14.7 mm at five years; p < .001). Patients treated outside the instructions for use (IFU) had significantly higher rates of migration, surgical conversion, and aneurysm sac expansion (p = .03).ConclusionThe Anaconda endograft provides high technical success and satisfactory five year aneurysm exclusion and clinical success rates. However, implantation outside the IFU should be avoided, as it leads to significantly worse outcomes, and caution over the risk of limb occlusion and distal embolisation should be observed.

Since December 2019, the global pandemic caused by the highly infectious novel coronavirus 2019-nCoV (COVID-19) has been rapidly spreading. As of April 2020, the outbreak has spread to over 210 countries, with over 2,400,000 confirmed cases and over 170,000 deaths [1]. COVID-19 causes a severe pneumonia characterized by fever, cough, and shortness of breath. Similar coronavirus outbreaks have occurred in the past causing severe pneumonia like COVID-19, most recently, severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). However, over time, SARS-CoV and MERS-CoV were shown to cause extra-pulmonary signs and symptoms including hepatitis, acute renal failure, encephalitis, myositis, and gastroenteritis. Similarly, sporadic reports of COVID-19 related extrapulmonary manifestations emerge. Unfortunately, there is no comprehensive summary of the multi-organ manifestations of COVID-19, making it difficult for clinicians to quickly educate themselves about this highly contagious and deadly pathogen. What's more, is that SARS-CoV and MERS-CoV are the closest humanity has come to combating something similar to COVID-19, however, there exists no comparison between the manifestations of any of these novel coronaviruses. In this review, we summarize the current knowledge of the manifestations of the novel coronaviruses SARS-CoV, MERS-CoV, and COVID-19, with a particular focus on the latter, and highlight their differences and similarities.

Zusammenfassung Hintergrund Pflegekräfte in Deutschland sind zunehmend von physischen und psychischen Belastungen beeinträchtigt, was sich negativ in den Krankheitstagen und Frühberentungszahlen niederschlägt. Im Projekt PFLEGEprevent wurde ein Präventionsprogramm entwickelt, das auf die speziellen Bedürfnisse des Pflegepersonals ausgerichtet ist, damit deren Ressourcen im Umgang mit Arbeitsbelastungen und Herausforderungen des beruflichen Alltags gestärkt werden. Das Präventionsprogramm wurde in einer RCT mit Pflegekräften implementiert und auf seine Wirksamkeit in den Bereichen Stress, Arbeitsfähigkeit und Lebensqualität hin evaluiert. Methodik Die randomisiert kontrollierte Interventionsstudie wurde im Wartegruppendesign mit 6 Erhebungszeitpunkten über 9 Monate durchgeführt. Die Datenerhebung der Zielgrößen erfolgte über validierte Instrumente: Perceived Stress Questionnaire (PSQ), Perceived Stress Scale (PSS), Work Ability Index (WAI), Erholungs-Belastungs-Fragebogen für den Arbeitskontext (EBF-Work 27), Short-Form-Health Survey (SF-12) und WHO-Five Well-Being Index (WHO-5). Neben deskriptiven Analysen wurde der t-Test für unabhängige Stichproben verwendet, um die Veränderungen in der primären und den sekundären Zielgrößen zwischen den Studiengruppen zu vergleichen. Ergebnisse Es nahmen 125 (92% weiblich, Durchschnittsalter 46,7 Jahre) Pflegekräfte an der Studie teil. Es zeigten sich signifikante Gruppenunterschiede in den Veränderungen der Zielgröße zu den Follow-up-Messungen bis zu 9 Monaten. Besonders das Stressempfinden reduzierte sich in der Interventionsgruppe langfristig. Das allgemeine Wohlbefinden in dieser Gruppe verbesserte sich zu allen Erhebungszeitpunkten signifikant zum Ausgangswert. Schlussfolgerung Die Evaluation des Präventionsprogrammes zeigte noch nach 9 Monaten einen positiven Effekt in der gemessenen Zielgröße PSQ zum Stresserleben. In den weiteren Zielgrößen konnten signifikante Gruppenunterschiede zu den Nacherhebungszeitpunkten nach 1 und 3 Monaten gezeigt werden.

Aims:This study aims to understand the clinical and radiographic outcomes between patients treated with static and expandable interbody spacers with adjustable lordosis for minimally invasive (MIS) lateral lumbar interbody fusion (LLIF).Background:The use of large interbody spacers in MIS LLIF offers favorable clinical and radiographic results. Static interbody spacers may cause iatrogenic endplate damage and implant subsidence due to forceful impaction and excessive trialing. Expandable interbody spacers with adjustable lordosis offerin situexpansion that may optimize endplate contact and maximize and maintain sagittal alignment correction until fusion occurs.Objective:The objective of this study is to compare the clinical and radiographic outcomes between patients treated with static and expandable interbody spacers with adjustable lordosis for MIS LLIF.Methods:This is a multi-surgeon, retrospective, Institutional Review Board-exempt chart review of consecutive patients who underwent MIS LLIF at 1-2 contiguous level(s) using either a polyetheretherketone (PEEK) static (32 patients) or a titanium expandable spacer with adjustable lordosis (57 patients). The mean differences of radiographic and clinical functional outcomes were collected and compared from preoperative up to 12-month postoperative follow-up. Statistical results were significant if PResults:The mean improvement of VAS back pain scores from preoperative to 6 and 12 months was significantly higher in the expandable group compared to the static group (PConclusion:This study showed significant positive clinical and radiographic outcomes for patients who underwent MIS LLIF using titanium expandable interbody spacers with adjustable lordosis based on significant changes in VAS back pain scores, ODI scores, and radiographic parameters at 12-month follow-up. There was a 0% subsidence rate in the expandable group, compared to a 32% subsidence rate in the static group.

After decades when intensive chemotherapy remained the only effective anti-acute myeloid leukaemia (AML) treatment, a torrent of novel, less toxic agents are about to revolutionise AML therapy. Prolonged remissions with good quality of life become achievable for many patients previously considered only for palliative care because they could not tolerate intensive therapy. As treatment options multiply, the importance of genetic profile is recognised, even for advanced-age patients for whom cure is unlikely. With lack of randomised comparative trials for most treatment regimens, one can only extrapolate data from existing studies to make evidence-based decisions. We herein present seven common clinical scenarios illustrating the complexity of treating older AML patients and describe our approach to their management. In each case, up-to-date data on relevant agents to be offered to a particular patient are discussed. The current review is limited to the drugs, available and approved in the Western world and many promising agents, still under investigation, are not discussed.

Young children with attention deficit hyperactivity disorder (ADHD) cope with functional difficulties attributed to executive dysfunction. This study evaluates the feasibility of the Parental Occupational Executive Training (POET) intervention. Parents of 71 children (4–7 years) with ADHD attended 8 to 10 weekly, personally tailored intervention sessions with an occupational therapist. Quantitative and qualitative measures were used to examine feasibility in four indices: parental attendance, adherence, and acceptance, and therapist fidelity. Parental attendance and home-strategy use during daily activities rates were high. Parents identified the occupational performance coaching model’s principles as supporting their ability to implement the intervention. Therapists demonstrated high fidelity to the POET’s theoretical bases. The POET is a feasible intervention with high parental attendance (98.61%), parental adherence (80.56%–94.44%), and therapist fidelity (100.00%). It can be implemented within child development centers and occupational therapy clinics and leads to parents’ increased adherence.

Die objektive Erfassung subjektiv erlebter Schmerzen ist ein bislang unzureichend gelostes Problem. In den letzten Jahren wurden Datensatze erstellt, um Algorithmen der kunstlichen Intelligenz zu trainieren, welche Muster der Schmerzintensitat erkennen. Die multimodale Erkennung von Schmerzen mit maschinellen Lernverfahren konnte eine Moglichkeit bieten, eine Uber- bzw. Unterversorgung mit Analgetika zu verringern, explizit bei Patienten mit eingeschrankter Kommunikationsfahigkeit. In dieser Studie wurde die Methodik einer automatisierten multimodalen Erkennung von Schmerzintensitat und -modalitat mittels maschineller Lernverfahren der kunstlichen Intelligenz untersucht. Im Einzelnen wurden multimodale Erkennungsraten von experimentell induzierten phasischen Elektro- und Hitzeschmerzreizen mit uni- und bimodalen Erkennungsraten verglichen. Basierend auf der X‑ITE Pain Database wurden gesunde Probanden mit phasischem elektroinduziertem Schmerz und Hitzeschmerz stimuliert und die Schmerzreaktionen mit multimodaler Sensorik (akustisch, videobasiert, physiologisch) erfasst. Nach komplexer Signalverarbeitung wurden mit maschinellen Lernverfahren Erkennungsraten der Schmerzintensitat (Baseline vs. Schmerzschwelle, Schmerztoleranz, Mittelwert von Schmerzschwelle und -toleranz) und der Vergleich der Schmerzmodalitat elektrisch vs. Hitze berechnet. Letztendlich erfolgte ein statistischer Vergleich uni- vs. multimodaler sowie bi- vs. multimodaler Erkennungsraten. Multimodale Erkennungsraten der Schmerzintensitat sind uberwiegend den unimodalen Erkennungsraten signifikant uberlegen, unabhangig von der Schmerzmodalitat. Die multimodale Erkennung der Schmerzmodalitat unterscheidet signifikant besser zwischen hitze- und elektroinduziertem Schmerz. Multimodale Erkennungsraten sind des Weiteren uberwiegend den bimodalen Erkennungsraten uberlegen. Dem multimodalen Ansatz der Erkennung von Schmerzintensitat und -modalitat sollte im Vergleich zur Unimodalitat Vorrang gegeben werden. Es ist in weiteren klinischen Studien zu klaren, ob eine multimodale Erkennung von Schmerzintensitat und -modalitat einer bimodalen Erkennung tatsachlich uberlegen ist.

Background The Emergency Severity Index (ESI) is a widely used tool to triage patients in emergency departments. The ESI tool is used to assess all complaints and has significant limitation for accurately triaging patients with suspected acute coronary syndrome (ACS). Objective We evaluated the accuracy of ESI in predicting serious outcomes in suspected ACS and aimed to assess the incremental reclassification performance if ESI is supplemented with a clinically validated tool used to risk-stratify suspected ACS. Methods We used existing data from an observational cohort study of patients with chest pain. We extracted ESI scores documented by triage nurses during routine medical care. Two independent reviewers adjudicated the primary outcome, incidence of 30-day major adverse cardiac events. We compared ESI with the well-established modified HEAR/T (patient History, Electrocardiogram, Age, Risk factors, but without Troponin) score. Results Our sample included 750 patients (age, 59 ± 17 years; 43% female; 40% black). A total of 145 patients (19%) experienced major adverse cardiac event. The area under the receiver operating characteristic curve for ESI score for predicting major adverse cardiac event was 0.656, compared with 0.796 for the modified HEAR/T score. Using the modified HEAR/T score, 181 of the 391 false positives (46%) and 16 of the 19 false negatives (84%) assigned by ESI could be reclassified correctly. Conclusion The ESI score is poorly associated with serious outcomes in patients with suspected ACS. Supplementing the ESI tool with input from other validated clinical tools can greatly improve the accuracy of triage in patients with suspected ACS.

Introduction: Uveal melanoma (UM) is a rare and malignant intraocular tumour with a dismal prognosis. Despite a good control of the primary tumour by radiation or surgery, up to 50% of patients subsequently develop metastasis for which no efficient treatment is yet available.Methodology: To identify therapeutic opportunities, we performed an in vitro screen of 30 combinations of different inhibitors of pathways that are dysregulated in UM. Effects of drug combinations on viability, cell cycle and apoptosis were assessed in eight UM cell lines. The best synergistic combinations were further evaluated in six UM patient-derived xenografts (PDXs).Results: We demonstrated that the Bcl-2/X-L/W inhibitor (ABT263) sensitised the UM cell lines to other inhibitors, mainly to mammalian target of rapamycin (mTOR), mitogen-activated protein kinase kinase (MEK) and murine double minute 2 (MDM2) inhibitors. mTOR (RAD001) and MEK1/2 (trametinib) inhibitors were efficient as single agents, but their combinations with ABT263 displayed no synergism in UM PDXs. In contrast, the combination of ABT263 with MDM2 inhibitor (HDM201) showed a trend for a synergistic effect.Conclusion: We showed that inhibition of Bcl-2/X-L/W sensitised the UM cell lines to other treatments encouraging investigation of the underlying mechanisms. Furthermore, our findings highlighted Bcl-2/X-L/W and MDM2 co-inhibition as a promising strategy in UM. (C) 2019 The Author(s). Published by Elsevier Ltd.

The Veterans Affairs (VA) health system is vital to providing joint replacement care to our retired service members but has come under recent scrutiny. The purpose of this study was to compare the short-term outcomes after total hip arthroplasty (THA) and total knee arthroplasty (TKA) between the VA cohort and the general cohort.We retrospectively reviewed 10.460 patients with primary THA and TKA from the Veterans Affairs Corporate Data Warehouse. As a control group, we queried the American College of Surgeons-National Surgical Quality Improvement Program database and identified 58,820 patients with primary THA and TKA over the same time period. We compared length of stay, mortality rates, 30-day complication rates, and 30-day readmissions. We performed a multivariate logistic regression analysis to identify the independent effect of the VA system on adverse outcomes.Veterans are more likely to be men (93% versus 41%, P0.001) and have increased rates of medical comorbidities (all P0.001). The rate of short-term complications (all P0.001) were all higher in the VA cohort. When controlling for demographics and medical comorbidities, VA patients were more likely to have a readmission (P0.001), prolonged length of stay4 days (P0.001), and experience a complication within 30 days (P0.001).Despite controlling for higher rates of medical comorbidities, VA patients undergoing primary THA and TKA had poorer short-term outcomes than the civilian cohort. Additional research is needed to ensure our veteran cohort is appropriately optimized and address the discrepancy with the outcomes of the civilian.