Miracle-dz/UniFAR-FTUs huggingface dataset:
Cost-effectiveness of nivolumab monotherapy in the third-line treatment of small cell lung cancer

Abstract Aims Present cost-effectiveness analysis of nivolumab monotherapy vs. commonly prescribed third-line (3 L+) treatment in small cell lung cancer (SCLC). Materials and methods A three health states partitioned survival model (progression-free, progressed disease, and death; US payer perspective) was developed. The systematic literature review identified no randomized controlled or single-arm trials with separate outcomes for 3 L + SCLC patients. Topotecan was chosen as a comparator because it is frequently prescribed in real-world practice for 3 L SCLC. Clinical inputs for topotecan were derived from the Flatiron database with inclusion/exclusion criteria matched to patients treated with 3 L + nivolumab in CheckMate 032. Intravenous (IV) and oral topotecan clinical efficacy were assumed equivalent. Base-case analysis used a 20-year lifetime horizon. An annual discount rate of 3.0% for costs and outcomes was applied. Uncertainty was assessed using sensitivity analyses adjusted for key parameters. Results Incremental cost per quality-adjusted life-year (QALY) gained with nivolumab was US$153,312 vs. IV topotecan and US$123,003 vs. oral topotecan, respectively. When results were disaggregated, nivolumab-related costs were mainly driven by drug acquisition costs, and topotecan-related costs were primarily due to adverse event treatment. Mean overall survival (OS) was 21.69 months with nivolumab and 5.80 months with IV or oral topotecan. More favorable outcomes were found by the landmark response analyses. Deterministic sensitivity analyses showed that changes to the discount rate for costs and outcomes and body weight had the greatest impacts on results. Limitations Included use of real-world data for OS outcomes associated with 3 L topotecan, use of second-line topotecan data for progression-free survival, and no indirect costs. Conclusions Based on the literature on willingness-to-pay for a QALY in metastatic cancer, nivolumab monotherapy might represent a cost-effective option for 3 L + treatment of SCLC compared with IV and oral topotecan. Sensitivity analysis using response-based methods yielded further favorable cost-effectiveness estimates.
A trial‐based economic evaluation of peppermint oil for the treatment of irritable bowel syndrome

Abstract Background Irritable Bowel Syndrome (IBS) is a prevalent, chronic gastrointestinal disorder that imposes a substantial socioeconomic burden. Peppermint oil is a frequently used treatment for IBS, but evidence about cost‐effectiveness is lacking. Objective We aimed to assess cost‐effectiveness of small‐intestinal release peppermint oil versus placebo in IBS patients. Methods In a multicenter randomized placebo‐controlled trial, cost‐effectiveness was evaluated from a societal perspective. The incremental cost‐effectiveness ratios (ICERs) were expressed as (1) incremental costs per Quality Adjusted Life Years (QALY), and (2) incremental costs per successfully treated patient, that is per abdominal pain responder (according to FDA definitions), both after an eight‐week treatment period with placebo versus peppermint oil. Cost‐utility and uncertainty were estimated using non‐parametric bootstrapping. Sensitivity analyses were performed. Results The analysis comprised 126 patients (N = 64 placebo, N = 62 small‐intestinal release peppermint oil). Peppermint oil was a dominant treatment compared to placebo in 46% of bootstrap replications. Peppermint oil was also more effective but at higher cost in 31% of replications. The net‐benefit acceptability curve showed that peppermint oil has a 56% probability of being cost‐effective at a conservative willingness‐to‐pay threshold of €10.000/QALY. Peppermint oil was also a dominant treatment per additional successfully treated patient according to FDA definitions, that is in 51% of replications. In this case, the acceptability curve showed an 89% probability of being cost‐effective. Conclusions In patients with IBS, small‐intestinal release peppermint oil appears to be a cost‐effective treatment although there is uncertainty surrounding the ICER. When using abdominal pain responder as outcome measure for the ICER, peppermint oil has a high probability of being cost‐effective. The use of peppermint oil, which is a low‐cost treatment, can be justified by the modest QALY gains and slightly higher proportion of abdominal pain responders. More research and long‐term data are necessary to confirm the cost‐effectiveness of peppermint oil. NCT02716285.
Health-related quality of life in osteoarthritis patients: a systematic review and meta-analysis

ABSTRACT The aim of this meta-analysis was to compare health-related quality of life (HRQoL) of Osteoarthritis (OA) patients and controls. A systematic literature search was performed on PubMed, Web of Science and EMBASE from database inception to 7 January 2020. Random effect model was performed to summarize the scores of each domain and the forest plot was used to compare the scores of OA patients with healthy controls. Subgroup analyses were conducted to explore the source of heterogeneity. Statistical analyses were executed using Review Manager (version 5.1). In total, six studies were included in this study, including 7094 patients with OA and 12 100 healthy controls, which were all reliable to summarize the scores of the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36). Meta-analyses found that pooled mean HRQoL score for the SF-36 each domain (physical function, physical role function, body pain, general health, vitality, social function, emotional role function, mental health) was lower in patients with OA than in healthy controls, especially the score in the dimension of physical role function. OA have a substantial impact HRQoL. HRQoL is a significant component of measuring overall health, which contributes to formulate successful self-disease management plan, patient-centered care, and develop effective interventions target confidence.
Virtual reality gaming in rehabilitation after stroke – user experiences and perceptions

Abstract Purpose The present study explored participants’ experiences with and perceptions of using fully immersive head-mounted virtual reality (VR) gaming as rehabilitation after stroke. Methods Four men and three women (median age 64 years) with chronic stroke and varying motor impairment (mild to severe) were interviewed after 10 weeks of VR training on the commercial HTC Vive system, focusing on the upper extremities. Inductive qualitative thematic analysis was performed. Results The analysis revealed three main themes: playing the game, benefits and effects, and personalizing the game. Playing the game encompasses both the feeling of being immersed in the game and descriptions of the gaming being motivating and fun. Benefits and effects describe the participants’ expectations of potential benefits, the importance of getting feed-back, and the impact in daily life. Personalizing the game includes finding the right game and level, and the participants’ need for support to achieve full use of the training. Conclusions Participants with chronic stroke described the fully immersive VR gaming intervention as a fun and motivating way to improve their functioning in everyday life. Qualitative studies are needed to explore how people with stroke perceive VR gaming when it is implemented in real clinical environments. Clinical implications VR gaming was perceived as a positive and motivating rehabilitation after stroke. Getting feedback and perceiving benefits are essential parts of VR rehabilitation. Commercial fully immersive VR-games might be an option for stroke rehabilitation when the game can be personalized and support is available.
Jammed keplerian gas leads to the formation and disappearance of spiral arms in a coupled map lattice for astronomical objects

The formation and disappearance of spiral arms are studied by focusing on jammed Keplerian gas in a coupled map lattice (CML) with a minimal set of procedures for simulating diverse patterns in astronomical objects. The CML shows that a spiral arm is a type of traffic jam, and its motion is governed by both a gas inflow into and outflow from the jam. In particular, we present a new approach to simply and directly evaluating the disappearance of spiral arms, called “light-in and heavy-out”. It is based on the gas flow rate difference between the light inflow and heavy outflow leading to the disappearance of traffic jams. Furthermore, we propose an approximate formula for the remaining lifetime of spiral arms, which is immediately derived from the “light-in and heavy-out” approach without calculating their pattern speeds as in conventional differential rotation. The proposed formula is successfully applied to the CML simulations.
Sexual Violence and Other Complications of Corona Virus in Amhara Metropolitan Cities, Ethiopia

Background The onset of corona virus (COVID-19) pandemic brought about multiple crises with financial, social, and political dimensions, and problems involving absence or scarcity of medication, food, and other amenities. COVID led to reports of severe hunger, stress, sexual violence, and associated complications. This study was aimed at assessing the prevalence of sexual violence, hunger, stress, indoor fighting, and related complications caused by the corona virus, and determining factors associated with it. Methods A cross-sectional design study involving a total of 1288 participants recruited from Amhara Metropolitan cities was implemented. Each participant completed a questionnaire regarding experience of sexual violence, hunger, stress, indoor fighting, and other complications faced due to COVID-19. A statistical analysis was done by fitting binary logistic regression model, independent t-test and Chi-squared test. Results From the total participants, 1288 (26.2%) were displaced, while 39.9% were unemployed due COVID-19. About half of the participants (48.8%) experienced general distress, 33.8% faced sexual violence, 18.2% experienced hunger, 8.4% faced indoor fighting. The majority (81.7%) of non-corona virus patients in government health-care institutions faced lack of treatment. For every unit increase of monthly income during COVID-19, the estimated odds of participants experiencing sexual violence decreased by 31.3% (aOR=0.687). Educational level, work status, and monthly salary before and during corona virus were important factors of hunger. Conclusion COVID-19 pandemic led to considerably high prevalence of sexual violence, hunger, stress, and indoor fighting. Work status of participants was an important associated factor of hunger, stress, and indoor fighting. Sex of participants and their monthly income were significantly associated with increase in sexual violence during COVID-19. In addition to a general economic recession, a decrease in treatment of non-COVID-19 patients was noticed, particularly in government hospitals.
Lasting Effects: Seven Year Results of the Castrop Nomogram for Femtosecond Laser-Assisted Paired Corneal Arcuate Incisions

ABSTRACT Purpose Long-term results of arcuate incisions are rarely reported. This is unfortunate as long-term stability of astigmatic correction is of great interest to surgeons performing astigmatic correction. This study investigates the 7 year stability of results after application of femtosecond laser-assisted arcuate incisions with the Castrop nomogram. Methods Prospective interventional case series at the Augen- und Laserklinik, Castrop-Rauxel, Germany. Single site, single surgeon study. Seven year results of cataract patients with low to moderate corneal astigmatism receiving femtosecond laser‐assisted arcuate incisions using a TechnolasVictus SW 2.7 (Bausch & Lomb Inc, Dornach, Germany) were assessed and compared to 1 year results. Outcome evaluation was based on astigmatic vector analysis, manifest refraction, and visual acuity. Results The study analyzed 19 eyes of 19 patients 7 years after surgery. Ocular residual astigmatism changed from −0.26 to −0.39 D. Preoperative corneal astigmatism was −1.51 D. Correction Index changed from 1.0 to 1.16. The magnitude of difference vector changed from 0.26 to 0.39 D. The index of success changed from 0.20 to 0.29. Spherical equivalent remained stable. A slight tendency to change toward astigmatic overcorrection was mainly observed for patients with preoperative with the rule astigmatism, but not with patients with against the rule astigmatism. Conclusions The Castrop nomogram showed stable results 7 years after surgery. Similar to toric IOL surgery, it is advisable to be less aggressive when correcting with the rule astigmatism, to avoid overcorrection over a long period.
Targeting enhancer reprogramming to mitigate MEK inhibitor resistance in preclinical models of advanced ovarian cancer.

Ovarian cancer is characterized by aberrant activation of the mitogen-activated protein kinase (MAPK), highlighting the importance of targeting the MAPK pathway as an attractive therapeutic strategy. However, the clinical efficacy of MEK inhibitors is limited due to intrinsic or acquired drug resistance. Here, we established patient-derived ovarian cancer models resistant to MEK inhibitors and demonstrated that resistance to the clinically-approved MEK inhibitor trametinib was associated with enhancer reprogramming. We also showed that enhancer decommissioning induced the downregulation of negative regulators of the MAPK pathway, leading to constitutive ERK activation and acquired resistance to trametinib. Epigenetic compound screening uncovered that HDAC inhibitors could alter the enhancer reprogramming and upregulate the expression of MAPK negative regulators, resulting in sustained MAPK inhibition and reversal of trametinib resistance. Consequently, a combination of HDAC inhibitor and trametinib demonstrated a synergistic anti-tumor effect in vitro and in vivo, including patient-derived xenograft mouse models. These findings demonstrated that enhancer reprogramming of the MAPK regulatory pathway might serve as a potential mechanism underlying MAPK inhibitor resistance and concurrent targeting of epigenetic pathways and MAPK signaling might provide an effective treatment strategy for advanced ovarian cancer.
Risk of a permanent work-related disability pension after incident venous thromboembolism in Denmark: A population-based cohort study

Background Long-term complications of venous thromboembolism (VTE) hamper physical function and impair quality of life; still, it remains unclear whether VTE is associated with risk of permanent work-related disability. We aimed to assess the association between VTE and the risk of receiving a permanent work-related disability pension and to assess whether this association was explained by comorbidities such as cancer and arterial cardiovascular disease. Methods and findings A Danish nationwide population-based cohort study consisting of 43,769 individuals aged 25 to 66 years with incident VTE during 1995 to 2016 and 218,845 birth year-, sex-, and calendar year-matched individuals from the general population, among whom 45.9% (N = 120,540) were women, was established using Danish national registries. The cohorts were followed throughout 2016, with permanent work-related disability pension as the outcome. Hazard ratios (HRs) with 95% confidence intervals (CIs) for disability pension were computed and stratified by sex and age groups (25 to 34, 35 to 44, 45 to 54, and 55 to 66 years of age) and adjusted for comorbidities and socioeconomic variables. Permanent work-related disability pensions were granted to 4,415 individuals with VTE and 9,237 comparison cohort members (incidence rates = 17.8 and 6.2 per 1,000 person-years, respectively). VTE was associated with a 3-fold (HR 3.0, 95% CI: 2.8 to 3.1) higher risk of receiving a disability pension. Adjustments for socioeconomic status and comorbidities such as cancer and cardiovascular diseases reduced the estimate (HR 2.3, 95% CI: 2.2 to 2.4). The risk of disability pension receipt was slightly higher in men than in women (HR 2.5, 95% CI: 2.3 to 2.6 versus HR 2.1, 95% CI: 2.0 to 2.3). As this study is based on medical and administrative registers, information on post-VTE care, individual health behavior, and workplace factors linked to disability pension in the general population are lacking. Furthermore, as disability pension schemes vary, our results might not be directly generalizable to other countries or time periods. Conclusions In this study, incident VTE was associated with increased risk of subsequent permanent work-related disability, and this association was still observed after accounting for comorbidities such as cancer and cardiovascular diseases. Our results emphasize the social consequences of VTE and may help occupational and healthcare professionals to identify vulnerable individuals at risk of permanent exclusion from the labor market after a VTE event.
EventPoint: Self-Supervised Local Descriptor Learning for Event Cameras

—We proposes a method of extracting intrest points and descriptors using self-supervised learning method from frame-based event data, which is called EventPoint. Different from other feature extraction methods on event data, we train our model on real event-form driving dataset–DSEC with the self-supervised learning method we proposed, the training progress fully consider the characteristics of event data.To verify the effectiveness of our work,we conducted several complete evaluations: we emulated DART and carried out feature matching experiments on N-caltech101 dataset, the results shows that the effect of EventPoint is better than DART; We use Vid2e tool provided by UZH to convert Oxford robotcar data into event-based format, and combined with INS information provided to carry out the global pose estimation experiment which is important in SLAM. As far as we know, this is the ﬁrst work to carry out this challenging task. Sufﬁcient experimental data show that EventPoint can get better results while achieve real time on CPU.
Cardiovascular Risk Associated With Ibrutinib Use in Chronic Lymphocytic Leukemia: A Population-Based Cohort Study

PURPOSE Ibrutinib reduces mortality in chronic lymphocytic leukemia (CLL). It increases the risk of atrial fibrillation (AF) and bleeding and there are concerns about heart failure (HF) and central nervous system ischemic events. The magnitude of these risks remains poorly quantified. METHODS Using linked administrative databases, we conducted a population-based cohort study of Ontario patients who were treated for CLL diagnosed between 2007 and 2019. We matched ibrutinib-treated patients with controls treated with chemotherapy but unexposed to ibrutinib on prior AF, age ≥ 66 years, anticoagulant exposure, and propensity for receiving ibrutinib. Study outcomes were AF-related health care contact, hospital-diagnosed bleeding, new diagnoses of HF, and hospitalizations for stroke and acute myocardial infarction (AMI). The cumulative incidence function was used to estimate absolute risks. We used cause-specific regression to study the association of ibrutinib with bleeding rates, while adjusting for anticoagulation as a time-varying covariate. RESULTS We matched 778 pairs of ibrutinib-treated and unexposed patients with CLL (N = 1,556). The 3-year incidence of AF-related health care contact was 22.7% (95% CI, 19.0 to 26.6) in ibrutinib-treated patients and 11.7% (95% CI, 9.0 to 14.8) in controls. The 3-year risk of hospital-diagnosed bleeding was 8.8% (95% CI, 6.5 to 11.7) in ibrutinib-treated patients and 3.1% (95% CI, 1.9 to 4.6) in controls. Ibrutinib-treated patients were more likely to start anticoagulation after the index date. After adjusting for anticoagulation as a time-varying covariate, ibrutinib remained positively associated with bleeding (HR, 2.58; 95% CI, 1.76 to 3.78). The 3-year risk of HF was 7.7% (95% CI, 5.4 to 10.6%) in ibrutinib-treated patients and 3.6% (95% CI, 2.2 to 5.4) in controls. There was no significant difference in the risk of ischemic stroke or AMI. CONCLUSION Ibrutinib is associated with higher risk of AF, bleeding, and HF, but not AMI or stroke. [Social Media Editor: Please insert the up arrow emoji here. ] risk of #afib, bleeding, #heartfailure, but not stroke or MI with ibrutinib use in CLL #cardioonc
Reactive Langerhans Cell Proliferation Mimicking Langerhans Cell Histiocytosis in Association with Sézary Syndrome: A Case Report and Literature Review

Abstract Sézary syndrome (SS) is a rare type of cutaneous T-cell lymphoma (CTCL) that is characterized by erythroderma, lymphadenopathy and circulating clonal T-cells (Sézary cells). However, to our knowledge, reactive Langerhans cell (LC) proliferation mimicking Langerhans cell histiocytosis (LCH) associated with SS has not been reported. In this report, we describe an unusual case of reactive LC proliferation mimicking LCH associated with SS in a 57-year-old female patient. With complaints of recurrent skin symptoms and enlarged lymph nodes (LNs), she was admitted to our center with a presumptive diagnosis of LCH as demonstrated by LN biopsy pathology. However, other than adenopathy, no lesions were noted in any organ system commonly involved in LCH. Typical Sézary cells were identified through morphology and further confirmed by flow cytometric immunophenotyping in peripheral blood (PB) and bone marrow (BM). In addition, T-cell receptor gene rearrangement was positive, whereas the BRAF V600E gene mutation was negative in skin, LN, PB and BM. The patient was ultimately diagnosed with SS with reactive LC proliferation. This case should remind clinicians to be wary of diagnosing LCH if LCH-like pathology occurs exclusively in LNs. Moreover, morphologic, immunologic, cytogenetic and molecular biologic studies should be performed to avoid misdiagnosis.
Mast cells: Therapeutic targets for COVID‐19 and beyond

Mast cells (MCs) are innate immune cells that widely distribute throughout all tissues and express a variety of cell surface receptors. Upon activation, MCs can rapidly release a diverse array of preformed mediators residing within their secretory granules and newly synthesize a broad spectrum of inflammatory and immunomodulatory mediators. These unique features of MCs enable them to act as sentinels in response to rapid changes within their microenvironment. There is increasing evidence now that MCs play prominent roles in other pathophysiological processes besides allergic inflammation. In this review, we highlight the recent findings on the emerging roles of MCs in the pathogenesis of coronavirus disease‐2019 (COVID‐19) and discuss the potential of MCs as novel therapeutic targets for COVID‐19 and other non‐allergic inflammatory diseases.