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STUDY OBJECTIVES: Excessive daytime sleepiness (EDS) is a treatment target for many patients with obstructive sleep apnea (OSA). We aimed to understand the prevalence, risk factors, and quality of life associated with EDS in a nonclinical, “real world” sample of patients with OSA. METHODS: Cross-sectional survey of patients with OSA participating in an online peer support community, assessing demographics, comorbidities, treatment, and quality of life. Differences in those with and without EDS (Epworth Sleepiness Scale > and ≤ 10) were assessed. RESULTS: The sample (n = 422) was 54.2% male, 65.9% were ≥ 55 years, and 43.3% reported sleeping ≤ 6 hours/night. EDS was identified among 31.0% of respondents and 51.7% reported sleepiness as a precipitating factor for seeking initial OSA treatment. EDS was more prevalent in individuals reporting asthma, insomnia symptoms, positive airway pressure (PAP) use less than 6 hours/night on ≥ 5 nights/week, or sleep duration < 6 hours/night. After adjusting for demographics and comorbidities, patients with EDS reported poorer mental and physical health and well-being, lower disease-specific functional status, more activity and work impairment, and more driving impairment (P values < .05). In the subsample (n = 265) with high PAP adherence, 26.0% reported EDS, and similar associations between EDS and outcomes were observed. CONCLUSIONS: These “real world” data suggest that patients seeking online OSA support experience a high prevalence of EDS, which was associated with poorer quality of life and worse functional status. Associations persisted among respondents with high self-reported PAP-therapy adherence, potentially driving these individuals to seek online support for sleepiness-related symptoms. CITATION: Wanberg LJ, Rottapel RE, Reid ML, et al. Prevalence of sleepiness and associations with quality of life in patients with sleep apnea in an online cohort. J Clin Sleep Med. 2021;17(12):2363–2372.

BACKGROUND The aim of this study was to evaluate the impact of different therapy regimens, including sodium oxybate (SXB)-containing regimens, on patient-reported outcomes (PROs) in people with narcolepsy. METHODS Online surveys were used to collect information from persons with narcolepsy in the Nexus Narcolepsy Registry. Surveys contained questionnaires assessing self-reported sleep quality (SQ; via single question), daytime sleepiness and function (Epworth Sleepiness Scale and Functional Outcomes of Sleep Questionnaire), health-related quality of life (HRQoL; 36-Item Short Form Health Survey [SF-36]), work productivity and impairment (Work Productivity and Activity Impairment: Specific Health Problem), and history of injuries or motor vehicle accidents. Treatment with SXB (including monotherapy or combination therapy; SXB group) was compared with non-SXB therapy (No SXB group). The P values presented are nominal, as there are no adjustments for multiplicity. RESULTS From June 2015 through December 2017, 983 participants completed 1760 surveys. SQ and daytime functioning scores were better in the SXB group compared with the No SXB group (all P

Background Obstructive sleep apnea (OSA) is associated with excessive daytime sleepiness (EDS), which may go undiagnosed and can significantly impair a patient’s health-related quality of life (HRQOL). This qualitative research examined timing and reasons patients sought medical care for their EDS and OSA symptoms, and the impact of EDS on HRQOL. Methods Focus groups were conducted in 3 US cities with 42 participants currently experiencing EDS with OSA. Transcripts were coded and analyzed using an adapted grounded theory approach common to qualitative research. Results Over three-fifths of study participants (n = 26, 62%) were currently using a positive airway pressure (PAP) or dental device; one-third (n = 14, 33%) had previously used a positive airway pressure (PAP) or dental device, and the remainder had either used another treatment (n = 1, 2%) or were treatment naïve (n = 1, 2%). Twenty-two participants (52%) reported experiencing OSA symptoms for ≥1 year, with an average duration of 11.4 (median 8.0, range 1–37) years before seeking medical attention. Several (n = 7, 32%) considered their symptoms to be “normal,” rather than signaling a serious medical condition. Thirty participants (71%) discussed their reasons for ultimately seeking medical attention, which included: input from spouse/partner, another family member, or friend (n = 20, 67%); their own concern about particular symptoms (n = 7, 23%); and/or falling asleep while driving (n = 5, 17%). For all 42 participants, HRQOL domains impacted by EDS included: physical health and functioning (n = 40, 95%); work productivity (n = 38, 90%); daily life functioning (n = 39, 93%); cognition (n = 38, 90%); social life/relationships (n = 37, 88%); and emotions (n = 30, 71%). Conclusions Findings suggest that patients may be unaware that their symptoms could indicate OSA requiring evaluation and treatment. Even following diagnosis, EDS associated with OSA can continue to substantially affect HRQOL and daily functioning. Further research is needed to address diagnostic delays and unmet treatment needs for patients with EDS associated with OSA.

Physiological variations in people with type 1 diabetes constantly change the insulin requirements of patients which, if not compensated, can lead to insulin overdose or insulin insufficiency causi...

This study analyzed a privately insured pediatric population with and without narcolepsy to determine the impact of pediatric narcolepsy on comorbidities, health care utilization, and cost. Additional analyses compared narcolepsy type 1 and type 2.This retrospective cross-sectional study identified US patients with narcolepsy18 years of age with ≥2 claims with a diagnosis code of narcolepsy using Truven MarketScan® data 2011 to 2015. Patients were matched to controls without narcolepsy. Comorbid conditions, health care utilization, and costs were measured by calendar year. P values are nominal, and no adjustments for multiplicity or multiple comparisons were made.A total of 1427 pediatric patients with narcolepsy were identified and matched with 4281 controls from 2011 to 2015. Patients with narcolepsy had more comorbid conditions (mean 5.8 vs 2.4, nominal P 0.001). Respiratory diseases and mood disorders were more common in patients with narcolepsy than controls (57% vs 32% and 56% vs 14%, respectively; both nominal P 0.001). Compared to controls, patients with narcolepsy underwent more diagnostic tests (electroencephalogram, EEG [0.13 vs 0.0053]) and brain computed tomography, CT/magnetic resonance imaging, MRI (0.26 vs 0.022; both nominal P 0.001). Mean annual inpatient days (0.71 vs 0.15), emergency department visits (0.51 vs 0.15), and outpatient office visits (8.6 vs 2.3) were higher for patients with narcolepsy than controls (all nominal P 0.001). Annual mean health care costs were higher for patients with narcolepsy versus controls ($15,797 vs $2449, nominal P 0.001).Pediatric patients with narcolepsy had greater comorbidity, higher health care utilization, and higher costs than patients without narcolepsy.

Background The Lombardy region has been one of the Italian regions most affected by the COVID-19 pandemic in 2020, with 22.7% of total Italian cases and 33.9% of total deaths. The emergency healthcare system was under deep stress throughout the period under consideration due to the admission of COVID-19 patients to the Emergency Department (ED) and had to be thoroughly reorganized. Methods We performed a retrospective descriptive analysis of patients admitted into the ED recorded in the Lombardy online regional portal called EUOL. We compared the data registered in the EUOL with the patients admitted to the EDs from 1 January 2019 to 31 December 2019 and from 1 January 2020 to 31 December 2020. Results The number of admissions to the ED decreased by 32.5% in 2020 compared to 2019, reaching the lowest number in March and April. However, the percentage of patients hospitalised after ED significantly increased in 2020 compared to 2019 (OR 1.47, p < 0.0001), reflecting the management of patients with a more severe clinical condition. Indeed, the number of patients classified as red or yellow codes at hospital admission was significantly higher in 2020 than in 2019 (p < 0.0001). Moreover, more patients arrived at the ED by ambulance in 2020 (21.7% in 2020 versus 15.1% in 2019. OR 1.56, p < 0.0001), with more than 35% of patients transported by ambulance in March and April 2020. Conclusions Our results showed, on the one hand, inappropriate visits to the EDs by non-emergency and low complex cases in 2019 before the pandemic and, on the other hand, they also highlighted that patients in critical condition were reluctant to visit the ED due to the fear of getting infected. This analysis showed that EMS played a crucial role in the overall public health impact of the COVID-19 pandemic, increasing the percentage of patients transported to the hospital with a severe clinical condition, reorganizing and allocating resources to the areas that were most affected during the pandemic. Key messages This is a descriptive analysis of the public health impact of the COVID-19 pandemic on the admission to Emergency Departments in 2020. Our results underline the need to monitor the pandemic’s evolution in order to reorganize the hospitals that admitted the COVID-19 patients.

Background: The indications for intracranial pressure (ICP) monitoring in patients with acute brain injury and the effects of ICP on patients’ outcomes are uncertain. The aims of this study were to describe current ICP monitoring practises for patients with acute brain injury at centres around the world and to assess variations in indications for ICP monitoring and interventions, and their association with long-term patient outcomes. Methods: We did a prospective, observational cohort study at 146 intensive care units (ICUs) in 42 countries. We assessed for eligibility all patients aged 18 years or older who were admitted to the ICU with either acute brain injury due to primary haemorrhagic stroke (including intracranial haemorrhage or subarachnoid haemorrhage) or traumatic brain injury. We included patients with altered levels of consciousness at ICU admission or within the first 48 h after the brain injury, as defined by the Glasgow Coma Scale (GCS) eye response score of 1 (no eye opening) and a GCS motor response score of at least 5 (not obeying commands). Patients not admitted to the ICU or with other forms of acute brain injury were excluded from the study. Between-centre differences in use of ICP monitoring were quantified by using the median odds ratio (MOR). We used the therapy intensity level (TIL) to quantify practice variations in ICP interventions. Primary endpoints were 6 month mortality and 6 month Glasgow Outcome Scale Extended (GOSE) score. A propensity score method with inverse probability of treatment weighting was used to estimate the association between use of ICP monitoring and these 6 month outcomes, independently of measured baseline covariates. This study is registered with ClinicalTrial.gov, NCT03257904. Findings: Between March 15, 2018, and April 30, 2019, 4776 patients were assessed for eligibility and 2395 patients were included in the study, including 1287 (54%) with traumatic brain injury, 587 (25%) with intracranial haemorrhage, and 521 (22%) with subarachnoid haemorrhage. The median age of patients was 55 years (IQR 39–69) and 1567 (65%) patients were male. Considerable variability was recorded in the use of ICP monitoring across centres (MOR 4·5, 95% CI 3·8–4·9 between two randomly selected centres for patients with similar covariates). 6 month mortality was lower in patients who had ICP monitoring (441/1318 [34%]) than in those who were not monitored (517/1049 [49%]; p

To address the study of the deployment of publicly accessible Automated External Defibrillators (AED), Geomatics allows computing their limited area of effectiveness (i.e. ‘catchment area’, CA), traditionally set as circular surfaces with a 100m-radius. Exploiting open geospatial data related to roads network, also ‘realistic’ CAs, based on the effective walking distance, can be computed. Aim of this study (performed on the territory of Lombardy, Italy, total surface 23,863.65 km2, with open source software as QGIS, PostGIS, pgRouting) was to compare the two approaches, and to evaluate if the territory analysis could support case-by-case decision-making about the preferable mapping technique.Setting a limit of 200 m, realistic CAs were computed for 7702 known AEDs on the territory (at 28/02/2018). The mean area obtained resulted close to that of the traditional 100m-radius circular area (33,665m2 against 31,415m2), but the spatial coverage of 45043 OHCAs - Out-of-Hospital Cardiac Arrests (Lombardy, 1/1/2015 to 31/12/2018) is very different considering realistic or circular areas (15.35% vs 9.43%). The distribution of the mapping error (realistic-CA – circular-CA) and the computation failures of realistic areas were studied and correlated with the characteristics of the surrounding territory considering attributes related to streets, buildings, and land-use, computing linear correlation coefficients and performing Mann-Whitney U-tests. Results suggest that realistic CAs are not always correctly computable and circular areas are preferable when AEDs are far from the streets in less urbanized and more uniform territories. An automatized decision-making about the best case-by-case mapping technique is therefore feasible with open data and open source software.

The European Union and the European Space Agency (EU/ESA) have promoted since 1998 (Baveno Manifesto*) the GMES Programme (Global Monitoring for Environment and Security), nowadays called Copernicus (www.copernicus.eu). In the agriculture domain, the use of Copernicus Sentinel imagery and its services are providing several new opportunities. The knowledge of fundamentals of Earth Observation/Geographic Information EO/GI, namely Geomatics, for the development of innovative strategies for professional skills adequacy and capacity building, supporting Copernicus user uptake, becomes mandatory (Gomarasca, 2009). The target is to help bridging gaps between supply and demand of education and training for geospatial sector (www.eo4geo.eu). The innovative and strategical novelties are the complete free access to Sentinel time series imagery and digital image processing software “Sentinel toolboxes” such as SNAP (Sentinel Application Platform) for different environments (Windows, Mac, Unix). The paper introduce topics as crop mapping and monitoring, biophysical parameters, phenology and yield estimations, through several concluded or ongoing international projects such as: ERMES -FP7 (http://www.ermes-fp7space.eu/it/homepage/, Busetto et al. 2017) and SATURNO (https://www.progettosaturno.it/, Nutini et al., 2018) devoted to the regional agricultural monitoring. As conclusion, SNAP software for image processing of Sentinel data was demonstrated and tested together with Earth Engine software for specific vertical agriculture applications. The topics reported in this paper have been part of the Summer School ‘Sentinel for Applications in Agriculture’ supported by the Copernicus programme, several scientific associations (AIT, ASITA, EARSeL - European Association of Remote Sensing Laboratories), the European Erasmus+ project EO4GEO, University Departments and Geo-Information Companies.

Veno-occlusive disease (VOD), also called sinusoidal obstruction syndrome (SOS), is a potentially life-threatening complication of hematopoietic stem cell transplantation (HSCT) conditioning or high-dose nontransplant chemotherapy. VOD/SOS with multi-organ dysfunction (MOD) is associated with a mortality rate of > 80%. Defibrotide (25 mg/kg/day) is approved to treat hepatic VOD/SOS with renal or pulmonary dysfunction post HSCT in the United States and to treat severe hepatic VOD/SOS in patients > 1 month of age in the European Union. A random effects model was used for pooling data from 17 systematically chosen defibrotide studies. For patients in these reports (n = 2598), and those in the subset of 10 reports of patients treated with ~ 25 mg/kg/day (n = 1691), estimated Day + 100 survival rates were 54% and 56%, respectively. Among those patients treated with ~ 25 mg/kg/day, estimated Day + 100 survival was 44% among patients with MOD and 71% in patients without MOD; survival was 41% and 70%, respectively, for the population of patients receiving any dose of defibrotide. Safety results were not pooled owing to differences in reporting methodology but were generally consistent with the known tolerability profile of defibrotide. This analysis provides the largest assessment of survival in patients treated with defibrotide for VOD/SOS with or without MOD.

Background: There are no well-established chemotherapy regimens for metastatic triple negative breast cancer. The combination of a microtubule inhibitor (eribulin) with a nucleoside analog (gemcitabine) may synergistically induce tumor cell death, especially in tumors like triple negative breast cancers (TNBC) characterized by high cell proliferation, aggressive tumor behavior, and chemo-resistance. Materials and Methods:This is an open-label, national multicenter phase II study evaluating the combination of eribulin (0.88 mg/m2) plus gemcitabine (1000 mg/m2) on day 1 and 8, q21 as either first- or second-line treatment of locally advanced or metastatic TNBC.The primary endpoint was the objective response rate (ORR) for evaluable patients (pts). The study was designed according to the Simon's two stage optimal design. We chose the lower activity (p0) of 0.20 and target activity level (p1) of 0.35. A prospective, molecular correlative study has been being carried out on germinal DNA of study population to assess the role of BRCA mutations and single nucleotide polymorphisms (SNPs) in predicting efficacy and toxicity of the combination regimen. Results: From July 2013 to September 2016, 83 evaluable pts (37 in the first stage, 46 in the second one) were enrolled. They received a median number of 6 cycles of treatment (range 1-24). The ORR (CR+PR) was 37.35% (90% CI: 28.47-46.93) and the clinical benefit rate (CR+PR+SD ≥ 24wks) was 48.78% (90% CI: 39.24%-58.39%). The most common grade 3-4 adverse events (> 10% of patients) were neutropenia and liver toxicity. With a median follow-up of 28.8 months, the median progression-free survival (PFS) and overall survival (OS) were 5.1 months (95% CI: 4.2-7.0) and 14.7 months (95% CI: 10.2-20.0), respectively. BRCA1/2 deleterious mutations were observed in 15 (22%) out of 68 genotyped pts. Women with BRCA1/2 mutations were associated with worse ORR, PFS and OS than those with BRCA1/2 wild-type. A panel of SNPs in genes of study drug metabolism pathways was evaluated. Among these, CYP3A4 392A >G and FGD4 2044236G>A SNPs were associated with greater liver toxicity by logistic regression analysis. Furthermore, CDA*2 79A>C, RRM1 2455 A>G, and CYP2C8 416G>A SNPs were associated with poorer overall survival by Cox proportional hazards model. Conclusions:The combination of eribulin and gemcitabine shows promising activity and a moderate toxicity profile in metastatic TNBC. BRCA status and pharmacogenetics tests may help identify pts with high probability of response with negligible toxicity. Citation Format: Musolino A, Cavanna L, Boggiani D, Zamagni C, Frassoldati A, Caldara A, Rocca A, Gori S, Piacentini F, Berardi R, Brandes AA, Foglietta J, Villa F, Pellegrino B, Todeschini R, Tognetto M, Naldi N, Bortesi B, Boni L, Montemurro F, Ardizzoni A. Phase II study of eribulin in combination with gemcitabine for the treatment of patients with locally advanced or metastatic triple negative breast cancer (ERIGE Trial). Clinical and pharmacogenetic results on behalf of the Gruppo Oncologico Italiano di Ricerca Clinica (GOIRC) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-14-05.

In this work, we study the presence of surface modes in two different photonic crystal waveguides characterized by the presence of layers of a dispersive left-handed material. The periodicity required to have a photonic crystal waveguide is considered in two distinct ways. One of them is composed of two perfect electrical conducting rippled surfaces, and the other consists of two at infinite surfaces that surround a periodic one-dimensional array of circular cylindrical inclusions of a perfect electrical conductor, coated with a layer of left-handed material. To study these systems, integral numerical methods were applied to determine their band structures and the electromagnetic field distribution, under the TE and TM polarizations. Numerical results show the presence of surface modes for several frequencies with certain geometric configurations. One of these frequencies is known in the literature and corresponds to the frequency of a Surface Plasmon-Polariton.

Background The Lombardy region has been the Italian region most affected by the coronavirus disease 2019 (COVID-19) pandemic in 2020. The emergency healthcare system was under deep stress throughout the past year due to the admission of COVID-19 patients to the emergency department (ED) and had to be thoroughly reorganized. Methods We performed a retrospective descriptive analysis of patients admitted into the ED recorded in the Lombardy online regional portal called EUOL (Emergenza e Urgenza OnLine). We compared the data registered in the EUOL with the patients admitted to the EDs from 1 January 2019 to 31 December 2019 and from 1 January 2020 to 31 December 2020. Results The number of admissions to the ED decreased by 32.5% in 2020 compared with 2019, reaching the lowest number in March and April. However, the percentage of patients hospitalized after ED significantly increased in 2020 compared with 2019 (P Conclusions This analysis showed the importance of monitoring the pandemic’s evolution in order to treat more critically ill patients, despite a lower number of patients.

Oncolytic virus therapy aims to treat cancer using viruses. This promising therapy is weakened by clinical challenges related to dosage, toxicity, and uncertain tumor dynamics. The interactions between oncolytic viruses and tumor cells are described by mathematical models to advance understanding of treatment outcomes and design better therapies. Motivated by the urgent need to improve clinical outcomes, this letter proposes a nonlinear estimation and control scheme to determine doses of viral injections by applying impulsive control theory. The scheme is designed by using the extended Kalman filter and nonlinear model predictive control (MPC). The MPC relies on a model of oncolytic adenovirus therapy, where the model parameters have been identified by fitting the model to experimental data from five nude mice. The proposed scheme determines optimal viral doses, which tend to enforce better and faster tumor regression than former protocols. Moreover, this scheme delivers personalized therapy which is robust to some parameter and modeling uncertainty. Together, the findings of this letter stand as an in-silico proof-of-concept to develop control engineering approaches, which help to resolve clinical challenges of oncolytic virus therapies.

We examine the use of chipless RFID tags for plastic identification in two applications in the recycling chain. First, on a conveyor belt system, where tagged plastics pass by a reader one at a time. We demonstrate that our approach can successfully differentiate between 2 plastic types with over 90% accuracy and is agnostic to tag orientation or contaminants such as oil and water. In doing so, we show that the technology works just as well or is superior to comparable studies using optical methods. Second, for contents estimation, where we estimate the relative fraction of two types of plastics in a bulk mixture. We show that we are able to detect pure or homogeneous bales of plastic with over 90% accuracy and estimate the content of non-homogeneous bales with 65-75% accuracy. This could help recycling plant managers prioritize sorting operations based on composition of incoming shipments with more information than they have currently. Future directions of research are also discussed.

Current technological advances have brought closer to reality the project of a safe, portable, and efficient artificial pancreas for people with type 1 diabetes (T1D). Among the developed control strategies for T1D, model predictive control (MPC) has been emphasized in literature as a promising control for glucose regulation. However, these control strategies are commonly designed in a computer environment, regardless of the limitations of a portable device. In this paper, the performances of six embedded platforms and three open-source optimization solver algorithms are assessed for T1D treatment. Their advantages and limitations are clarified using four MPC formulations of increasing complexity and a hardware-in-the-loop methodology to evaluate glucose control in virtual adult subjects. The performance comparison includes the execution time, the difference concerning the evolution obtained in MATLAB, the processor temperature, energy consumption, time percentage in normoglycemia, and the number of hypo- and hyperglycemic events. Results show that Quadprog is the package that faithfully follows the results obtained with control strategies designed and tuned on a computer with the MATLAB software. In addition, the Raspberry Pi 3 and the Tinker Board S embedded systems present the appropriate characteristics to be implemented as portable devices in the artificial pancreas application according to the criteria set out in this work.

Septic shock represents the vast majority of the cases of shock in intensive care unit (ICU) patients and is a life-threatening condition needing prompt recognition and treatment to provide adequate oxygen utilization to the cells. Initial characterization of sepsis-associated cardiovascular dysfunction was based on clinical patterns identified by physical examination; however, the use of invasive and, more recently, non-invasive tools for hemodynamic assessment at the bedside allowed a more comprehensive evaluation of this clinical condition. The heart is one of the organs most frequently failing in sepsis; however, depending on the definition used, the prevalence of sepsis-induced cardiac dysfunction may vary between 10% and 70%. In this context, several alterations in intracellular signaling pathway mechanisms have been proposed to explain the pathophysiology of septic cardiomyopathy, affecting the cytosolic calcium (Ca2+) and/or myofilament function and cardiac contractile force. Mitochondrial function is also significantly impacted by sepsis. These broad-spectrum micro derangements are associated with even greater variation in macroscopic heart dysfunction patterns, although finding a normal study is not unusual. For this reason, echocardiography plays a pivotal role in septic shock patients, identifying the clinical patterns related to acute right or left ventricular dysfunction. The available literature has shown that diastolic dysfunction and, potentially, right ventricular dysfunction may play a more important role in prognostication of heart damage than acute systolic left ventricular dysfunction, which is quite common, often reversible, and not associated with mortality.

This study examined the correlation between improvements in excessive daytime sleepiness in participants with obstructive sleep apnea or narcolepsy and changes in functional status, work productivity and health‐related quality of life. Data from two 12‐week randomized controlled trials of solriamfetol were analyzed. Participants completed the Epworth Sleepiness Scale, 10‐item Functional Outcomes of Sleep Questionnaire, Work Productivity and Activity Impairment questionnaire and 36‐Item Short Form Health Survey and performed the Maintenance of Wakefulness Test at baseline and weeks 4, 8 and 12. Patient Global Impression of Change was assessed at weeks 4, 8 and 12. Pearson correlations were calculated for change in scores from baseline to week 12. For both studies, changes in the 10‐item Functional Outcomes of Sleep Questionnaire were highly correlated (absolute value >0.5) with changes in Epworth Sleepiness Scale scores; changes in multiple domain scores of the 36‐Item Short Form Health Survey and Work Productivity and Activity Impairment questionnaire were moderately correlated (0.3–0.5) with changes in Epworth Sleepiness Scale scores in both studies and highly correlated for participants with narcolepsy. Changes in Maintenance of Wakefulness Test scores correlated moderately with changes in Epworth Sleepiness Scale scores in both studies. At week 12, Patient Global Impression of Change ratings correlated highly with Epworth Sleepiness Scale and 10‐item Functional Outcomes of Sleep Questionnaire scores for both disorders. Other correlations were low. Self‐reported assessments of sleepiness and global improvement appear to be more strongly correlated with measures of functioning and health‐related quality of life than objectively assessed sleepiness.

The EEG has showed that contains relevant information about recognition of emotional states. It is important to analyze the EEG signals to understand the emotional states not only from a time series approach but also determining the importance of the generating process of these signals, the location of electrodes and the relationship between the EEG signals. From the EEG signals of each emotional state, a functional connectivity measurement was used to construct adjacency matrices: lagged phase synchronization (LPS), averaging adjacency matrices we built a prototype network for each emotion. Based on these networks, we extracted a set node features seeking to understand their behavior and the relationship between them. We found through the strength and degree, the group of representative electrodes for each emotional state, finding differences from intensity of measurement and the spatial location of these electrodes. In addition, analyzing the cluster coefficient, degree, and strength, we find differences between the networks from the spatial patterns associated with the electrodes with the highest coefficient. This analysis can also gain evidence from the connectivity elements shared between emotional states, allowing to cluster emotions and concluding about the relationship of emotions from EEG perspective.

Oncolytic virus therapy aims to eradicate tumours using viruses which only infect and destroy targeted tumour cells. It is urgent to improve understanding and outcomes of this promising cancer treatment because oncolytic virus therapy could provide sensible solutions for many patients with cancer. Recently, mathematical modelling of oncolytic virus therapy was used to study different treatment protocols for treating breast cancer cells with genetically engineered adenoviruses. Indeed, it is currently challenging to elucidate the number, the schedule, and the dosage of viral injections to achieve tumour regression at a desired level and within a desired time frame. Here, we apply control theory to this model to advance the analysis of oncolytic virus therapy. The control analysis of the model suggests that at least three viral injections are required to control and reduce the tumour from any initial size to a therapeutic target. In addition, we present an impulsive control strategy with an integral action and a state feedback control which achieves tumour regression for different schedule of injections. When oncolytic virus therapy is evaluated in silico using this feedback control of the tumour, the controller automatically tunes the dose of viral injections to improve tumour regression and to provide some robustness to uncertainty in biological rates. Feedback control shows the potential to deliver efficient and personalized dose of viral injections to achieve tumour regression better than the ones obtained by former protocols. The control strategy has been evaluated in silico with parameters that represent five nude mice from a previous experimental work. Together, our findings suggest theoretical and practical benefits by applying control theory to oncolytic virus therapy.

Aims: Treatment of acute myeloid leukemia (AML) requires significant healthcare resource utilization (HRU), including lengthy hospitalizations. In a phase 3 study (NCT01696084), CPX-351 (Vyxeos) sh...

A risk score identifying patients at high risk for veno-occlusive disease (VOD) may aid efforts to study preventive strategies for this uncommon complication of hematopoietic cell transplantation (HCT). Patients receiving a first allogeneic HCT between 2008 and 2013 as reported to the Center for International Blood and Marrow Transplant Research (N = 13,097) were randomly divided into training and validation sets. Independent prognostic factors for development of VOD by day +100 after HCT were identified with a multivariate logistic regression model. A risk score was constructed in the training set using the significant factors and confirmed in the validation set. Baseline characteristics of the training and validation sets were balanced. In total, 637 patients (4.9%) developed VOD by day +100. Younger age, positive hepatitis B/C serology, lower Karnofsky performance scale score, use of sirolimus, disease, disease status at transplant, and conditioning regimen were independent prognostic factors. Myeloablative conditioning regimens were associated with higher risk of VOD. Busulfan-based myeloablative conditioning regimens guided by pharmacokinetic monitoring were associated with higher risk than those without pharmacokinetic monitoring. Patients were stratified into 4 distinct, statistically significantly different groups by their risk score percentile. This pretransplant risk score successfully stratified allogeneic HCT patients by risk of developing VOD, was validated in an independent set, and demonstrated strong discriminatory ability to identify a high-risk cohort.

Veno-occlusive disease (VOD), also called sinusoidal obstruction syndrome (SOS), is a potentially life-threatening complication of hematopoietic stem cell transplantation (HSCT) conditioning or high-dose nontransplant chemotherapy. VOD/SOS with multi-organ dysfunction (MOD) is associated with a mortality rate of 80%. Defibrotide (25 mg/kg/day) is approved to treat hepatic VOD/SOS with renal or pulmonary dysfunction post HSCT in the United States and to treat severe hepatic VOD/SOS in patients 1 month of age in the European Union. A random effects model was used for pooling data from 17 systematically chosen defibrotide studies. For patients in these reports (n = 2598), and those in the subset of 10 reports of patients treated with ~ 25 mg/kg/day (n = 1691), estimated Day + 100 survival rates were 54% and 56%, respectively. Among those patients treated with ~ 25 mg/kg/day, estimated Day + 100 survival was 44% among patients with MOD and 71% in patients without MOD; survival was 41% and 70%, respectively, for the population of patients receiving any dose of defibrotide. Safety results were not pooled owing to differences in reporting methodology but were generally consistent with the known tolerability profile of defibrotide. This analysis provides the largest assessment of survival in patients treated with defibrotide for VOD/SOS with or without MOD.

Introduction Narcolepsy patients report lower health-related quality of life (HRQoL) than the general population, as measured by the Short Form-36 Health Survey (SF-36). This analysis evaluated whether changes in SF-36 correlated with physician-rated Clinical Global Impression of Change (CGI-C). Methods Data were from 209 of 228 narcolepsy patients participating in an 8-week clinical trial of sodium oxybate. Changes from baseline for SF-36 subscales (Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional, and Mental Health) and the summary scores were evaluated for correlation with CGI-C overall and by treatment group. Correlations were calculated using the Pearson product-moment correlation coefficient (r). Results Correlations described an inverse relationship in scores, but a direct relationship in improvement; lower CGI-C scores (i.e., better) were associated with higher SF-36 subscale scores (i.e., improved HRQoL). Moderate and significant correlations were observed for Vitality (r = −0.464; P

A Phase-3 study of defibrotide compared with historical controls demonstrated a 23% improvement in 100-day survival post-hematopoietic stem cell transplantation (HSCT) among patients with veno-occlusive disease with multi-organ dysfunction (VOD with MOD).To estimate the budget impact and cost-effectiveness of introducing defibrotide to a transplant center.The authors developed a budget impact model from the perspective of a bone-marrow transplant center. It was estimated that 2.3% of adults and 4.2% of children would develop VOD with MOD following HSCT based on a retrospective hospital database analysis and the effect that treating patients with defibrotide would have on costs for adult and pediatric centers was estimated. A cost-utility analysis (CUA) was also developed to capture the long-term cost-effectiveness of defibrotide. Projected life expectancies in the two groups were estimated based on trial data, transplant registry data, studies of long-term survival among HSCT patients, and US population life-tables.There was an estimated 3% increase ($330,706) per year in total adult transplantation center costs associated with adopting defibrotide, and a1% increase ($106,385) for pediatric transplant centers, assuming 100 transplants per year. In the CUA, the lifetime increase in cost per patient was $106,928, life expectancy increased by 3.74 years, and quality-adjusted life-years (QALYs) increased by 2.24. The incremental cost-effectiveness ratio (ICER) was $47,736 per QALY gained; 88% probability defibrotide was cost-effective at a $100,000/QALY threshold.The budget impact of defibrotide for a transplant center is relatively modest compared to the overall cost of transplantation. Defibrotide provides an important survival advantage for VOD with MOD patients, and the life years gained lead to defibrotide being highly cost-effective.

OBJECTIVE/BACKGROUND The real-world experience of people with narcolepsy is not well understood. PATIENTS/METHODS The Nexus Narcolepsy Registry (NCT02769780) is a longitudinal, web-based patient registry of self-reported data from adults with physician-diagnosed narcolepsy. Surveys were electronically distributed every 6 months; the current analysis reports registry population demographics, narcolepsy diagnosis journey, and predictors of diagnostic delays. RESULTS The registry population included in this analysis (N = 1024) was predominantly female (85%) and White (92%), with a mean age of 37.7 years. Most participants had education/training beyond high school (93%). Mean (median) reported ages at narcolepsy symptom onset, first consultation for symptoms, and narcolepsy diagnosis were 18.1 (16), 26.4 (24), and 30.1 (28) years, respectively. A majority (59%) of participants reported ≥1 misdiagnosis, and 29% reported consulting ≥5 physicians before narcolepsy diagnosis. More than half (56%) of participants' first consultations for narcolepsy symptoms were with a general practitioner, whereas the diagnosing clinician was usually a sleep specialist (64%) or neurologist (27%). Pediatric symptom onset was associated with a longer mean interval to first consultation than adult symptom onset (10.7 and 4.6 years, respectively; P

CPX-351 is a dual-drug liposomal encapsulation of cytarabine/daunorubicin. In a phase 3 study (ClinicalTrials.gov Identifier: NCT01696084), patients aged 60-75 years with newly diagnosed, high-risk/secondary AML received 1-2 induction cycles with CPX-351 or 7 + 3 chemotherapy; those achieving complete remission (including with incomplete platelet or neutrophil recovery) could receive up to 2 consolidation cycles with CPX-351 or 5 + 2 chemotherapy, respectively. In this exploratory analysis of the subgroup of patients who received consolidation, median overall survival was prolonged among patients receiving CPX-351 induction/consolidation versus 7 + 3/5 + 2 (25.43 vs. 8.53 months; HR = 0.44 [95% CI: 0.25-0.77]). The safety profile of CPX-351 consolidation was consistent with that of the overall study. Outpatient administration of CPX-351 consolidation occurred in 51%-61% of patients and did not diminish overall survival. These findings suggest consolidation with CPX-351 in this patient population contributed to the prolonged overall survival versus 7 + 3/5 + 2, building upon findings from the overall study population, and provide evidence that, with careful monitoring, some patients can successfully receive CPX-351 as outpatients.

This paper addresses the cerebral cortex maps construction from EEG signals getting an information simplification method for an emotional state phenomenon description. Bi-dimensional density distribution of main signal features are identified and a comparison to a previous approach is presented. Feature extraction scheme is performed via windowed EEG signals Stationary Wavelet Transform with the Daubechies Family (1–10); nine temporal and spectral descriptors are computed from the decomposed signal. Recursive feature selection method based on training a Random forest classifier using a one-vs-all scheme with the full features space, then a ranking procedure via gini importance, eliminating the bottom features and restarting the entire process over the new subset. Stopping criteria is the maximum accuracy. The main contribution is the analysis of the resulting subset features as a proxy for cerebral cortex maps looking for the cognitive processes understanding from surface signals. Identifying the common location of different emotional states in the central and frontal lobes, allowing to be strong parietal and temporal lobes differentiators for different emotions.

Unsupervised learning methods are commonly used to perform the non-trivial task of uncovering structure in biological data. However, conventional approaches rely on methods that make assumptions about data distribution and reduce the dimensionality of the input data. Here we propose the incorporation of entropy related measures into the process of constructing graph-based representations for biological datasets in order to uncover their inner structure. Experimental results demonstrated the potential of the proposed entropy-based graph data representation to cope with biological applications related to unsupervised learning problems, such as metagenomic binning and neuronal spike sorting, in which it is necessary to organize data into unknown and meaningful groups.

Objective Solriamfetol (formerly JZP-110), a dopamine/norepinephrine reuptake inhibitor, is approved in the US to improve wakefulness in adults with excessive daytime sleepiness associated with narcolepsy (75–150 mg/d) or obstructive sleep apnea (37.5–150 mg/d). In a randomized, double-blind, placebo-controlled trial in participants with narcolepsy, effects of solriamfetol on functional status, health-related quality of life (HRQoL), and work productivity were evaluated. Methods Participants with narcolepsy (N = 239) were randomized to solriamfetol 75, 150, or 300 mg, or placebo for 12 weeks. Outcome measures included the Functional Outcomes of Sleep Questionnaire short version (FOSQ-10), 36-Item Short Form Health Survey version 2 (SF-36v2), and Work Productivity and Activity Impairment questionnaire for Specific Health Problem (WPAI:SHP). A mixed-effects model with repeated measures was used for comparisons vs placebo. Results At week 12, solriamfetol increased FOSQ-10 total score, with greatest mean difference from placebo (95% CI) at 300 mg (1.45 [0.31, 2.59]). On SF-36v2, improvements vs placebo were observed in physical component summary scores (300 mg: 2.22 [0.04, 4.41]) and subscales of role physical, general health, and vitality. On WPAI:SHP, solriamfetol 150 mg reduced overall work impairment vs placebo (−15.5 [−29.52, −1.47]), and 150 and 300 mg reduced activity impairment vs placebo (−10.05 [−19.48, −0.62] and −13.49 [−23.19, −3.78], respectively). Most treatment-emergent adverse events (TEAEs) were mild or moderate in severity. Common TEAEs were headache, nausea, decreased appetite, nasopharyngitis, dry mouth, and anxiety. Conclusions Solriamfetol improved measures of functional status, HRQoL, and work productivity, particularly at the 150- and 300-mg doses. Most TEAEs were mild to moderate. Trial registration ClinicalTrials.gov identifier NCT02348593, EudraCT number 2014-005487-15.

Background: Obstructive sleep apnea (OSA) with excessive daytime sleepiness (EDS) can impair quality of life (QOL) and may go undiagnosed. Objectives: To examine the diagnosis experience and impacts of EDS with OSA on QOL in the US. Methods: Focus groups in 3 US cities with 42 patients experiencing EDS with OSA; coded transcripts qualitatively analysed using adapted grounded theory approach. Results: Prior to diagnosis, 40% (n=17) of patients were aware of their EDS and 74% (n=31) were informed of their other OSA symptoms by a spouse/partner, family or friends. About half (n=22, 52%) waited an average of 11.4 (range 1-37) years to seek medical care for OSA; 32% (n=7/22) had thought their symptoms were normal rather than a sign of OSA. Reasons for seeking care were: input from a loved one (n=21, 50%); self-concern about symptoms (n=7, 17%); and impaired driving (n=5, 12%). Twenty-seven patients discussed referral pathways: 15/27 (56%) first saw a primary care physician and 12/27 (44%) a specialist. Although 74% (n=31) were currently on OSA treatment, the majority reported EDS impacts on physical functioning (n=40, 95%); daily life (n=39, 93%); cognition (n=38, 90%); social life (n=37, 88%); and work (n=29, 69%). Conclusions: In the US, OSA diagnosis is often delayed, with many patients unaware of the need to seek medical care. Following OSA diagnosis, EDS may continue to impair QOL. Future research should address diagnostic delays and unmet treatment needs for this population.

Aims Leucocyte esterase (LE) has been shown to be an accurate marker of prosthetic joint infection (PJI), and has been proposed as an alternative to frozen section (FS) histology for intraoperative diagnosis. In this study, the intraoperative assessment of LE was compared with FS histology for the diagnosis of prosthetic hip infection. Patients and Methods A total of 119 patients undergoing revision total hip arthroplasty (THA) between June 2015 and December 2017 were included in the study. There were 56 men and 63 women with a mean age of 66.2 years (27 to 88). Synovial fluid was collected before arthrotomy for the assessment of LE using enzymatic colourimetric strips. Between five and six samples were stained with haematoxylin and eosin for FS histology, and considered suggestive of infection when at least five polymorphonuclear leucocytes were found in five high-power fields. Results The sensitivity and specificity of the LE assay were 100% and 93.8%, respectively; the positive (PPV) and the negative (NPV) predictive values were 79.3% and 100%, respectively. The mean time between the collection of the sample and the result being known was 20.1 minutes (sd 4.4). The sensitivity and specificity of FS histology were 78.3% and 96.9%, respectively; the PPV and the NPV were 85.7% and 94.9%, respectively. The mean time between the collection of the sample and the result being known was 27.2 minutes (sd 6.9). Conclusion The sensitivity of LE assay was higher, with similar specificity and diagnostic accuracy, compared with FS histology. The faster turnaround time, its ease of use, and low costs make LE assay a valuable alternative to FS histology. We now use it routinely for the intraoperative diagnosis of PJI. Cite this article: Bone Joint J 2019;101-B:372–377.

Visualizing the cluster structure of high-dimensional data is a non-trivial task that must be able to deal with the large dimensionality of the input data. Unlike hard clustering structures, visualization of fuzzy clusterings is not as straightforward because soft clustering algorithms yield more complex clustering structures. Here is introduced the concept of membership networks, an undirected weighted network constructed based on the fuzzy partition matrix that represents a fuzzy clustering. This simple network-based method allows understanding visually how elements involved in this kind of complex data clustering structures interact with each other, without relying on a visualization of the input data themselves. Experiment results demonstrated the usefulness of the proposed method for the exploration and analysis of clustering structures on the Iris flower data set and two large and unlabeled financial datasets, which describes the financial profile of customers of a local bank.

combination of Raman spectroscopy and PCA-SVM are feasible non-invasive diagnostic tool in diabetes to classify qualitatively high and low levels of HbA1c in vivo. In this study we identify and classify high and low levels of glycated hemoglobin (HbA1c) in healthy volunteers (HV) and diabetic patients (DP). Overall, 86 subjects were evaluated. The Raman spectrum was measured in three anatomical regions of the body: index fingertip, right ear lobe, and forehead. The measurements were performed to compare the difference between the HV and DP (22 well controlled diabetic patients (WCDP) (HbA1c

Purpose Adjuvant chemotherapy improves survival of patients with gastric cancer. Intergroup Trial of Adjuvant Chemotherapy in Adenocarcinoma of the Stomach (ITACA-S) was a phase III study comparing sequential FOLFIRI followed by docetaxel/cisplatin versus 5-fluorouracil monotherapy. The intensive regimen was not superior in terms of disease-free survival (DFS) and overall survival (OS). Methods The treatment was to be started within 8 weeks from surgery. This analysis evaluates the impact of time from surgery to chemotherapy start (TSC) on outcomes. Results Out of 1,106 randomized, 1,072 patients without major violations of eligibility criteria and receiving at least one treatment cycle were analyzed. Median TSC was 50 days. Chemotherapy was interrupted in 201 (18.8%) cases, whereas it was completed without or with modifications in 277 (25.8%) and 594 (55.4%), respectively. At a median follow-up of 56.9 months, 513 progressions and 472 deaths occurred. A longer TSC was significantly associated with longer DFS (hazard ratio [HR] 0.95; 95% confidence interval [CI] 0.89-1.00; p = 0.05) and OS (HR 0.91; 95% CI 0.86-0.97; p = 0.004), after adjustment for treatment arm, age, sex, primary tumor site, number of resected nodes, and tumor stage. Better treatment compliance was associated with improved survival. Conclusions Our findings suggest that longer TSC had at least no detrimental effect on DFS and OS, whereas treatment completion had a protective effect. Our findings need to be confirmed prospectively.

Background Congenital nasal pyriform aperture stenosis (CNPAS) is a rare cause of nasal obstruction in neonates with respiratory distress manifestations. Diagnosis is made with craniofacial computed tomography, prompt and precise treatment creates good outcomes in these patients. Aim To present our experience in diagnosis and management considerations with this rare pathology and a case series of our surgically managed patients. Methods A retrospective, analytical study of CNPAS patients surgically managed over a period of seven years. Evaluation and follow up was reviewed. Results Thirteen patients were evaluated; pyriform aperture mean width was 5.5 mm. Of these patients, 31% also had Congenital Midnasal Stenosis. Medical treatment failed for all the patients and they required surgical enlargement of the pyriform aperture. No complications were seen and all patients improved in symptoms and development. Conclusions Congenital nasal obstruction can be fatal in new-borns, CNPAS is a rare differential diagnosis that must be completely evaluated, properly treated with conservative management and if it fails, with well-planned and executed surgery. Follow-up shows high rates of success.

Synovial fluid analysis for diagnosis of prosthetic joint infections has gained increasing interest in the recent past when markers more specific for these infections than the serum ones have been identified. Despite the important steps forward, identification of a gold standard has not yet been identified. In this study, usefulness of alpha defensin, leukocyte esterase, C-reactive protein (CRP), and white blood cells (WBCs) in synovial fluids alone and in combination for diagnosis of prosthetic joint infection was evaluated. Synovial fluids from 32 infected and 34 not infected patients were analyzed. Sensitivity, specificity, positive and negative predictive values, diagnostic accuracy, and receiver-operating characteristic (ROC) curves were calculated for each parameter. Moreover, combination of coupled variables was also evaluated by logistic regression analysis. Sensitivity of alpha defensin, CRP, leukocyte count, and leukocyte esterase were 84.4%, 87.5%, 93.7%, and 93.8%, respectively. Specificity was 91.2% for leukocyte counts, 94.1% for alpha defensin, 97.0% for CRP, and 97.1% for leukocyte esterase. Diagnostic accuracy was 89.4% for alpha defensin, 92.4% for WBC counts and CRP, and 95.5% for leukocyte esterase. No statistical differences were observed in area under the curve (AUC) of the ROC curves of alpha defensin, CRP, and leukocyte counts. Logistic regression analysis applied to a model comprising all the variables showed an AUC higher than AUC of coupled variables. In conclusion, results of this study confirm the high sensitivity and specificity of synovial leukocyte esterase for diagnosis of prosthetic joint infection, also suggesting the need to assess a panel of markers to optimize diagnosis of these infections.

STUDY OBJECTIVES: Few population-based studies have explored how excessive sleepiness (ES) contributes to burden of illness among patients with obstructive sleep apnea (OSA). METHODS: This study utilized data from the annual, cross-sectional 2016 US National Health and Wellness Survey. Respondents self-reporting an OSA diagnosis were categorized as having ES (Epworth Sleepiness Scale [ESS] score ≥ 11) or not having ES (ESS score < 11). Comorbidities, health-related quality of life (HRQoL), and productivity were examined in three groups: OSA with ES (n = 731), OSA without ES (n = 1,452), and non-OSA controls (n = 86,961). RESULTS: The OSA with ES group had significantly higher proportions of respondents reporting depression (62.4% versus 48.0%), gastroesophageal reflux disease (39.0% versus 29.4%), asthma (26.3% versus 20.7%), and angina (7.8% versus 6.7%) compared to the OSA without ES group (P < .05). After controlling for covariates, the OSA with ES group had significantly lower (worse) scores for mental component score (41.81 versus 45.65 versus 47.81), physical component score (46.62 versus 48.68 versus 51.36), and SF-6D (0.65 versus 0.69 versus 0.73) compared with OSA without ES and non-OSA controls (all P < .001). The OSA with ES group had significantly higher (greater burden) mean rates of presenteeism (25.98% impairment versus 19.24% versus 14.75%), work impairment (29.41% versus 21.82% versus 16.85%), and activity impairment (31.09% versus 25.46% versus 19.93%) compared with OSA without ES and non-OSA controls (all P < .01) after controlling for covariates. CONCLUSIONS: OSA with ES is associated with higher prevalence of comorbidities, reduced HRQoL, and greater impairment in productivity compared to OSA without ES and compared to non-OSA controls. CITATION: Stepnowsky C, Sarmiento KF, Bujanover S, Villa KF, Li VW, Flores NM. Comorbidities, health-related quality of life, and work productivity among people with obstructive sleep apnea with excessive sleepiness: findings from the 2016 US National Health and Wellness Survey. J Clin Sleep Med. 2019;15(2):235–243.

In this work, we propose a two-dimensional photonic crystal–photonic crystal heterostructure that possesses the requirements for exciting an electromagnetic interface mode and investigate its interaction with photonic crystal waveguide modes. To study the interaction and coupling of both types of modes, the proper conditions to excite them are analyzed. Photonic crystal guided modes can appear in nearly any band gap when the photonic crystal has a line of defects within its lattice. Photonic crystal–photonic crystal surface modes can be excited at the junction of two different photonic crystals that share translation symmetry along the interface direction and have overlapped frequency band gaps. When this condition is met, dispersion relations of photonic crystal–photonic crystal surface modes will lie in the common region of both band gaps. Once the proper conditions are provided to excite these two modes, an interaction between them is possible. In the resulting calculations, a symmetric supercell and a plane wave basis are defined to numerically solve the wave equation.

Background: Schizophrenia is a debilitating disorder that often requires the affected individual to receive part- or full-time care from a caregiver. Aims: The purpose of this study was to examine the humanistic and economic burden of caring for an individual with Schizophrenia with regard to the measures of quality of life (QoL), work productivity, healthcare resource use and estimated economic costs. Methods: Data for this study came from the 2012 US National Health and Wellness Survey (NHWS; n = 71,149). Specifically, this analysis focused on those individuals in the survey who indicated that they were currently the primary caregiver for an individual with Schizophrenia (C-SCZ; n = 174). These individuals were matched via two separate 1:2 propensity score matches with both caregivers of other disorders (C-Other; n = 294) and non-caregivers (Non-C; n = 294) on significant covariates. Individuals were then compared across the outcomes of QoL, work productivity, healthcare resource use and estimated economic costs. Results: C-SCZ respondents had worse outcomes on all outcomes measured than C-Other respondents and Non-C respondents even when controlling for significant differences between the groups on sociodemographic characteristics. However, due to the small sample sizes, these comparisons were only significant in most cases for the C-SCZ to Non-C comparisons. Conclusion: Results indicate that caregivers of those with Schizophrenia experience a heightened humanistic and economic burden, especially relative to the burden experienced by non-caregivers. The fact that Schizophrenia not only affects the individual but also those who care for that individual is underscored by these results.

[EN] Comparisons of differential survival by country are useful in many domains. In the area of public policy, they help policymakers and analysts assess how much various groups benefit from public programs, such as social security and health care. In financial markets and especially for actuaries, they are important for designing annuities and life insurance products. This paper presents a method for clustering information about differential mortality by country. The approach is then used to group mortality surfaces for European Union (EU) countries. The aim of this paper is to measure between -group inequality in mortality experience in EU countries through a range of mortality indicators. Additionally, the indicators permit the characterization of each group. It is important to take into account characteristics such as sex; therefore, this study differentiates between males and females in order to detect whether their patterns and characterizations are different. It is concluded that there are clear differences in mortality between the east and west of the EU that are more important than the traditional south -north division, with a significant disadvantage for Eastern Europe, and especially for males in Baltic countries. We find that the mortality indicators have evolved in all countries in such a way that the gap between groups has been maintained, both in terms of the differences in mortality levels and variability. (C) 2017 Elsevier B.V. All rights reserved., This article was begun during a research stay at Cass Business School (London) funded by the "BEST/2014" Program, Generalitat Valenciana and the Facultad Support for the research presented in this paper was provided by a grant from the Ministry of Economy and Competitiveness, project MTM2013-45381-P.

Triple-negative breast cancer (TNBC) shows a very bad prognosis, even in early stages of disease. Metronomic chemotherapy refers to the minimum biologically effective dose of a chemotherapy agent given as a continuous dosing regimen with no prolonged drug-free breaks that leads to antitumor activity. In the present article, we review preclinical and clinical data of metronomic administration of chemotherapy agents with or without biological agents in TNBC cell lines and patients, contextually reporting data from the VICTOR-2 study in the subgroup of patients with TNBC, in order to stimulate new ideas for the design of clinical trials in this subset of patients.

Sinusoidal obstruction syndrome (SOS) is a life-threatening complication of hematopoietic stem cell transplantation (HSCT) associated with significant morbidity and mortality. Healthcare utilization, costs, and mortality were assessed in HSCT patients diagnosed with SOS, with and without multi-organ dysfunction (MOD).This retrospective observational study identified real-world patients undergoing HSCT between January 1, 2009 and May 31, 2014 using the Premier Healthcare Database. In absence of a formal ICD-9-CM diagnostic code, SOS patients were identified using a pre-specified definition adapted from Baltimore and Seattle criteria and clinical practice. Severe SOS (SOS/MOD) and non-severe SOS (SOS/no-MOD) were classified according to clinical evidence for MOD in the database.Of the 5,418 patients with a discharge diagnosis of HSCT, 291 had SOS, with 134 categorized as SOS/MOD and 157 as SOS/no-MOD. The remaining 5,127 patients had HSCT without SOS. Overall SOS incidence was 5.4%, with 46% having evidence of MOD. Distribution of age, gender, and race were similar between the SOS cohorts and non-SOS patients. After controlling for hospital profile and admission characteristics, demographics, and clinical characteristics, the adjusted mean LOS was 31.0 days in SOS/MOD compared to 23.9 days in the non-SOS cohort (medians = 26.9 days vs 20.8 days, p .001). The adjusted mean cost of SOS/MOD patients was $140,653, which was $41,702 higher than the non-SOS cohort (medians = $105,749 vs $74,395, p .001). An almost 6-fold increased odds of inpatient mortality was associated with SOS/MOD compared to the non-SOS cohort (odds ratio = 5.88; 95% CI = 3.45-10.33).Limitations of retrospective observational studies apply, since the study was not randomized. Definition for SOS was based on ICD-9 diagnosis codes from a hospital administrative database and reliant on completeness and accuracy of coding.Analysis of real-world data shows that SOS/MOD is associated with significant increases in healthcare utilization, costs, and inpatient mortality.

International audience; We report on the cryogenic characterization of Red Green Blue - High Density (RGB-HD) SiPMs developed at Fondazione Bruno Kessler (FBK) as part of the DarkSide program of dark matter searches with liquid argon time projection chambers. A cryogenic setup was used to operate the SiPMs at varying temperatures and a custom data acquisition system and analysis software were used to precisely characterize the primary dark noise, the correlated noise, and the gain of the devices. We demonstrate that FBK RGB-HD SiPMs with low quenching resistance (RGB-HD-LRq) can be operated from 40 K to 300 K with gains in the range 10(5) to 10(6) and noise rates at a level of around 1 Hz/mm(2).