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Passive acoustics are widely used to monitor the presence of dolphins in the marine environment. This study aims to introduce a low-cost and homemade approach for assembling a complete underwater microphone (i.e., the hydrophone), employing cheap and easy to obtain components. The hydrophone was assembled with two piezo disks connected in a balanced configuration and encased in a plastic container filled with plastic foam. The hydrophone's performance was validated by direct comparison with the commercially available AS-1 hydrophone (Aquarian Hydrophones, Anacortes, U.S.) on different underwater acoustic signals: artificial acoustic signals (ramp and multitone signals) and various dolphin vocalizations (whistle, echolocation clicks, and burst pulse signals). The sensitivity of the device's performance to changes in the emission source position was also tested. The results of the validation procedure on both artificial signals and real dolphin vocalizations showed that the significant cost savings associated with cheap technology had a minimal effect on the recording device's performance within the frequency range of 0–35 kHz. At this stage of experimentation, the global cost of the hydrophone could be estimated at a few euros, making it extremely price competitive when compared to more expensive commercially available models. In the future, this effective and low-cost technology would allow for continuous monitoring of the presence of free-ranging dolphins, significantly lowering the total cost of autonomous monitoring systems. This would permit broadening the monitored areas and creating a network of recorders, thus improving the acquisition of data. [ABSTRACT FROM AUTHOR]

Background: Muscle co-contraction plays a significant role in motion control. Available detection methods typically only provide information in the time domain. The current investigation proposed a novel approach for muscle co-contraction detection in the time–frequency domain, based on continuous wavelet transform (CWT). Methods: In the current study, the CWT-based cross-energy localization of two surface electromyographic (sEMG) signals in the time–frequency domain, i.e., the CWT coscalogram, was adopted for the first time to characterize muscular co-contraction activity. A CWT-based denoising procedure was applied for removing noise from the sEMG signals. Algorithm performances were checked on synthetic and real sEMG signals, stratified for signal-to-noise ratio (SNR), and then validated against an approach based on the acknowledged double-threshold statistical algorithm (DT). Results: The CWT approach provided an accurate prediction of co-contraction timing in simulated and real datasets, minimally affected by SNR variability. The novel contribution consisted of providing the frequency values of each muscle co-contraction detected in the time domain, allowing us to reveal a wide variability in the frequency content between subjects and within stride. Conclusions: The CWT approach represents a relevant improvement over state-of-the-art approaches that provide only a numerical co-contraction index or, at best, dynamic information in the time domain. The robustness of the methodology and the physiological reliability of the experimental results support the suitability of this approach for clinical applications. [ABSTRACT FROM AUTHOR]

Background: Muscular-activity timing is useful information that is extractable from surface EMG signals (sEMG). However, a reference method is not available yet. The aim of this study is to investigate the reliability of a novel machine-learning-based approach (DEMANN) in detecting the onset/offset timing of muscle activation from sEMG signals. Methods: A dataset of 2880 simulated sEMG signals, stratified for signal-to-noise ratio (SNR) and time support, was generated to train a hidden single-layer fully-connected neural network. DEMANN's performance was evaluated on simulated sEMG signals and two different datasets of real sEMG signals. DEMANN was validated against different reference algorithms, including the acknowledged double-threshold statistical algorithm (DT). Results: DEMANN provided a reliable prediction of muscle onset/offset in simulated and real sEMG signals, being minimally affected by SNR variability. When directly compared with state-of-the-art algorithms, DEMANN introduced relevant improvements in prediction performances. Conclusions: These outcomes support DEMANN's reliability in assessing onset/offset events in different motor tasks and the condition of signal quality (different SNR), improving reference-algorithm performances. Unlike other works, DEMANN's adopts a machine learning approach where a neural network is trained by only simulated sEMG signals, avoiding the possible complications and costs associated with a typical experimental procedure, making this approach suitable to clinical practice. [ABSTRACT FROM AUTHOR]

Background: Machine learning models were satisfactorily implemented for estimating gait events from surface electromyographic (sEMG) signals during walking. Most of them are based on inter-subject approaches for data preparation. Aim of the study is to propose an intra-subject approach for binary classifying gait phases and predicting gait events based on neural network interpretation of sEMG signals and to test the hypothesis that the intra-subject approach is able to achieve better performances compared to an inter-subject one. To this aim, sEMG signals were acquired from 10 leg muscles in about 10.000 strides from 23 healthy adults, during ground walking, and a multi-layer perceptron (MLP) architecture was implemented.Results: Classification/prediction accuracy was tested vs. the ground truth, represented by the foot-floor-contact signal provided by three foot-switches, through samples not used during training phase. Average classification accuracy of 96.1 ± 1.9% and mean absolute value (MAE) of 14.4 ± 4.7 ms and 23.7 ± 11.3 ms in predicting heel-strike (HS) and toe-off (TO) timing were provided. Performances of the proposed approach were tested by a direct comparison with performances provided by the inter-subject approach in the same population. Comparison results showed 1.4% improvement of mean classification accuracy and a significant (p < 0.05) decrease of MAE in predicting HS and TO timing (23% and 33% reduction, respectively).Conclusions: The study developed an accurate methodology for classification and prediction of gait events, based on neural network interpretation of intra-subject sEMG data, able to outperform more typical inter-subject approaches. The clinically useful contribution consists in predicting gait events from only EMG signals from a single subject, contributing to remove the need of further sensors for the direct measurement of temporal data. [ABSTRACT FROM AUTHOR]

Background: Urban dwellers represent half the world's population and are increasing worldwide. Their health and behaviours are affected by the built environment and green areas may play a major role in promoting physical activity, thus decreasing the burden of chronic diseases, overweight and inactivity. However, the availability of green areas may not guarantee healthy levels of physical activity among the urban dwellers. It is therefore necessary to study how the perceived characteristics of green areas affect physical activity. Methods: Data from the EURO-URHIS 2 survey of residents of 13 cities across the UK were analyzed and a multivariable model was created in order to assess the association between their perceptions of the green areas in their neighbourhood and their engagement in physical activity. Results were adjusted for age, gender and other potential confounders. Results: Those who felt unable to engage in active recreational activities in their local green spaces were significantly less likely to carry out moderate physical exercise for at least 60 min per week (adjusted OR: 0.50; 95% 0.37-0.68). Availability of green areas within walking distance did not affect engagement in physical activity. Other characteristics such as accessibility and safety may play an important role. Conclusion: This study showed that the presence of green space may not itself encourage the necessary preventative health behaviours to tackle physical inactivity in urban populations. Development of more appropriate green spaces may be required. Further research is needed to shed light on the types green spaces that are most effective. [ABSTRACT FROM AUTHOR]

Background: Self-reported health status (SRHS) reflects an individual's perception of their social, biological and psychological health, and has been linked to increased mortality risk and increased use of health services. Having a psychological co-morbidity can reduce health outcomes and increase healthcare costs. This paper investigates the relationship between SRHS and signs of psychological distress (PD) in European urban settings. Methods: The study sample comprised 20 439 adult respondents to surveys conducted across 37 urban areas. Data on SRHS, signs of PD and potential confounders were analysed in a multivariable logistic regression. Results: After adjusting for potential confounders (gender, age, time lived in country and regularity of contact with family and friends), a significant association was found between PD and self-reported poor health for all urban areas, particularly in Western European countries (adjusted OR = 3.615, 95% CI: 3.333-3.920 P < 0.001). Time lived in country of residence, financial stability and regularity of contact with family and friends were negatively associated with signs of PD in the adjusted model. Conclusions: There is a statistically significant association between self-reported poor health and signs of PD. Although the relationship was present in all geographical locations, the confounders were protective factors for Western European countries. Since the two factors are linked, interventions that target one might reduce the impact on both. Further study into causality would be of use in predicting future healthcare costs, which could be reduced by integrating their management. [ABSTRACT FROM AUTHOR]

Background: Reduced physical activity is a known risk factor for many illnesses. Research in adolescent populations found increased physical activity levels improves objective health outcomes, but there is conflicting evidence regarding the relationship between physical activity levels and self-reported health status. Aims: To synthesise current evidence on the association between physical activity and self-reported health status in adolescents. Secondary objectives are to assess whether the relationship is dose dependant, and the appropriateness of WHO recommendations on adolescents' physical activity. Methods: The main databases were searched using keywords for the main outcome of interest (health status, health behaviour and self-perception) and exposure of interest (motor activity, physical activity and exercise), supplemented with manual searches, secondary citation and reference searches. Quality appraisal was carried out using the Strengthening the Reporting of Observational Studies in Epidemiology checklist. Results: Eleven studies entered this review. Nine studies reported a significant relationship between increased levels of physical activity and improved self-reported health status, however two did not. Two studies followed up participants and found that the relationship persisted over time. Two papers described a dose-response relationship. Improvements in self-perceived health can be observed even below the current recommended levels of physical activity. Conclusion: The review supports initiatives to encourage adolescents to engage in physical activity as it improves self-reported health status. Sub- optimal levels of physical activity can also be beneficial. Further research should use standardised measurement scales and objectively measured physical activity levels. The roles of gender, income and culture should be further investigated. [ABSTRACT FROM AUTHOR]

A C-peptide-based assessment of β-cell function was performed here in the Zucker fatty rat, a suitable animal model of human metabolic syndrome. To this aim, a 90-min intravenous glucose tolerance test (IVGTT) was performed in seven Zucker fatty rats (ZFR), 7-to-9week-old, and seven age-matched Zucker lean rats (ZLR). The minimal model of C-peptide (CPMM), originally introduced for humans, was adapted to Zucker rats and then applied to interpret IVGTT data. For a comprehensive evaluation of glucose tolerance in ZFR, CPMM was applied in combination with the minimal model of glucose kinetics (GKMM). Our results showed that the present CPMM-based interpretation of data is able to: 1) provide a suitable fit of C-Peptide data; 2) achieve a satisfactory estimation of parameters of interest 3) quantify both insulin secretion by estimating the time course of pre-hepatic secretion rate, SR(t), and total insulin secretion, TIS, and pancreatic sensitivity by means of three specific indexes of β-cell responsiveness to glucose stimulus (first-phase, Ф1, second-phase, Ф2, and steady-state, Фss, never assessed in Zucker rats before; 4) detect the significant enhancement of insulin secretion in the ZFR, in face of a severe insulin-resistant state, previously observed only using a purely experimental approach. Thus, the methodology presented here represents a reliable tool to assess β-cell function in the Zucker rat, and opens new possibilities for the quantification of further processes involved in glucose homeostasis such as the hepatic insulin degradation. [ABSTRACT FROM AUTHOR]

The evolution with ageing of insulin resistance, body weight (BW) and mean arterial pressure (MAP) was studied in a group of Zucker fatty rats (ZFRs, n= 22), between 7 and 16 weeks of age, compared with an age-matched control group of Zucker lean rats (ZLRs, n= 22). The minimal model of glucose kinetics was applied to estimate glucose effectiveness, SG, and insulin sensitivity, SI, from insulinaemia and glycaemia measured during a 70 min intravenous glucose tolerance test. No correlation was found between SG and age in both ZFR and ZLR groups. No significant changes in mean SG between the two groups indicated no alteration of glucose-mediated glucose disposal. Estimates of SI from individual ZFRs were independent of age and, on average, showed 83% reduction ( P < 0.001) compared with the ZLR group. Despite the lack of alteration of SI with age, the ZFR group showed an age-related increase of MAP, which correlated with increasing BW (r = 0.71 and P < 0.001). These results support the hypothesis that in our ZFRs, as a suitable genetic model of obesity and hypertension, insulin resistance is fully established at the age of 7 weeks and remains practically unaltered until at least the sixteenth week. An age-related increase in arterial pressure, observed in this strain, relates more properly to increasing BW, rather than insulin resistance. Development of hypertension with increasing age and BW may result from an enhanced insulin-mediated activity of the sympathetic nervous system, as observed in our previously reported study. [ABSTRACT FROM AUTHOR]

Background: In the region of Piedmont, in Northern Italy, formal monitoring of antimicrobial stewardship (AMS) programs has been in place since 2012. The objective of our study was to provide an updated assessment of AMS programs operating in our region, and to assess the impact of the COVID-19 pandemic on stewardship activities. Methods: A retrospective observational study was conducted to investigate AMS programs implemented in acute-care trusts participating in a broader healthcare-associated infections and antimicrobial resistance (AMR) prevention and control program, promoted by the regional health department. Within this program, structure, process, and outcome indicators of AMS programs were investigated, using a previously developed scoring system. Differences between scores prior to (2019) and during the pandemic (2021) were assessed. Linear regression was used to assess whether the 5-year trends (2017–2021) in outcome measures in relation to structure and process scores were statistically significant. Compound annual growth rates (CAGR) for each outcome were calculated to illustrate changes in outcome rates over time. Results: All public trusts in the Region (20) and a small number of private institutions (3) provided data for this study. A modest, non-significant improvement was found for 2021 structure, process, and total scores compared to respective 2019 scores. A significant improvement was found concerning the definition of a formal mission statement, whereas significantly less trusts included monitoring adherence to antimicrobial policy or treatment guidelines in their programs. Overall consumption of antibiotics for systemic use saw an increase in 2021, with 2021 recording the highest median overall consumption compared to all previous years considered in this study. Methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant enterobacteria (CRE) rates decreased over the 5-year period. Significant downwards trends in MRSA rates were identified for high-outlier structure and process groups. Conclusions: Results of this study suggest AMS programs in Piedmont were not set back following the pandemic. This outcome was possible thanks to well-established programs, coordinated within a regional framework. Continued efforts should be dedicated to supporting AMS programs and contrasting AMR, even when the focus is shifted towards other public health emergencies. [ABSTRACT FROM AUTHOR]

Background: In the region of Piedmont, in Northern Italy, formal monitoring of antimicrobial stewardship (AMS) programs has been in place since 2012. The objective of our study was to provide an updated assessment of AMS programs operating in our region, and to assess the impact of the COVID-19 pandemic on stewardship activities. Methods: A retrospective observational study was conducted to investigate AMS programs implemented in acute-care trusts participating in a broader healthcare-associated infections and antimicrobial resistance (AMR) prevention and control program, promoted by the regional health department. Within this program, structure, process, and outcome indicators of AMS programs were investigated, using a previously developed scoring system. Differences between scores prior to (2019) and during the pandemic (2021) were assessed. Linear regression was used to assess whether the 5-year trends (2017–2021) in outcome measures in relation to structure and process scores were statistically significant. Compound annual growth rates (CAGR) for each outcome were calculated to illustrate changes in outcome rates over time. Results: All public trusts in the Region (20) and a small number of private institutions (3) provided data for this study. A modest, non-significant improvement was found for 2021 structure, process, and total scores compared to respective 2019 scores. A significant improvement was found concerning the definition of a formal mission statement, whereas significantly less trusts included monitoring adherence to antimicrobial policy or treatment guidelines in their programs. Overall consumption of antibiotics for systemic use saw an increase in 2021, with 2021 recording the highest median overall consumption compared to all previous years considered in this study. Methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant enterobacteria (CRE) rates decreased over the 5-year period. Significant downwards trends in MRSA rates were identified for high-outlier structure and process groups. Conclusions: Results of this study suggest AMS programs in Piedmont were not set back following the pandemic. This outcome was possible thanks to well-established programs, coordinated within a regional framework. Continued efforts should be dedicated to supporting AMS programs and contrasting AMR, even when the focus is shifted towards other public health emergencies. [ABSTRACT FROM AUTHOR]

Background: In November 2022, Italy participated in the third edition of the European Centre for disease prevention and control (ECDC) point prevalence survey (PPS) of healthcare-associated infections (HAIs) in acute-care hospitals. A questionnaire based on the WHO infection prevention and control assessment framework (IPCAF) was included, which aims to investigate multimodal strategies for the implementation of IPC interventions. Methods: A PPS was conducted using the ECDC PPS protocol version 6.0. The Regional health authority of the region of Piedmont, in north-western Italy, chose to enlist all public acute-care hospitals. Data were collected within one day per each ward, within 3 weeks in each hospital, at hospital, ward and patient level. A score between 0–1 or 0–2 was assigned to each of the 9 items in the IPCAF questionnaire, with 14 points representing the best possible score. HAI prevalence was calculated at the hospital-level as the percentage of patients with at least one HAI over all included patients. Relations between HAI prevalence, IPCAF score, and other hospital-level variables were assessed using Spearman's Rho coefficient. Results: In total, 42 acute-care hospitals of the region of Piedmont were involved, with a total of 6865 included patients. All participant hospitals reported they employed multimodal strategies to implement IPC interventions. The median IPCAF overall score was 11/14 (interquartile range, IQR: 9.25–12). The multimodal strategy with the highest level of adherence was education and training, followed by communication and reminders. Strategies with the lowest level of adherence were safety climate and culture of change, and system change. Overall HAI prevalence was 8.06%. A weak to moderate inverse relation was found between IPCAF score and HAI prevalence (Spearman's Rho -0.340, p 0.034). No other significant correlation was found. Conclusions: This study found a high self-reported overall level of implementation of multimodal strategies for IPC in the region. Results of this study suggest the relevance of the multimodal approach and the validity of the IPCAF score in measuring IPC programs, in terms of effectiveness of preventing HAI transmission. [ABSTRACT FROM AUTHOR]

Background: Engaging in regular physical activity has a beneficial impact on both physical health and on subjective health indicators. The aims of this study were (i) to assess the association between physical activity levels and self- reported health status in European adolescents and (ii) to identify any differences in the distribution of adolescents reporting good health between active and inactive subjects across urban areas. Methods: The study sample comprised 13 783 15-year olds from 21 urban areas across Europe who participated in the European Urban Health Indicators System Part 2 youth survey in 2010/11. Data collected on physical activity levels, self-rated health status and covariates including gender, BMI, socioeconomic status and sedentary behaviour were analyzed in a multivariable logistic regression model. Results: High levels of physical activity (OR: 1.607, 95% CI: 1.245-2.074, P<0.001) were associated with self-rated 'good health' across the cohort as a whole. All cities except lasi showed a positive association between high levels of physical activity and good health. This was significant in four cases: Amsterdam, Cardiff, Greater Manchester and Merseyside (P=0.035, 0.016, 0.010 and 0.049, respectively). Only 13.3% of the cohort met the current WHO physical activity level recommendations. Conclusion: High levels of physical activity are positively associated with self-rated 'good health' status in European adolescents. Alarming levels of physical inactivity make it a priority to encourage greater engagement in physical activity. Promotion of physical activity should be specifically tailored to each urban area. [ABSTRACT FROM AUTHOR]

Introduction. This study aims to investigate the reasons that discourage the patients affected by OSAS to undergo orthognathic surgery and compares the postoperative discomfort of phase I (soft tissue surgery) and phase II (orthognathic surgery) procedures for treatment of OSAS. Material and Methods. A pool of 46 patients affected by OSAS was divided into two groups: “surgery patients” who accepted surgical treatments of their condition and “no surgery patients” who refused surgical procedures. The “surgery patients” group was further subdivided into two arms: patients who accepted phase I procedures (IP) and those who accepted phase II (IIP). To better understand the motivations behind the refusal of II phase procedures, we asked the patients belonging to both the IP group and “no surgery” group to indicate the main reason that influenced their decision to avoid II phase procedures. We also monitored and compared five parameters of postoperative discomfort: pain, painkiller assumption, length of hospitalization, foreign body sensation, and diet assumption following IP and IIP procedures. Results. The main reason to avoid IIP procedures was the concern of a more severe postoperative discomfort. Comparison of the postoperative discomfort following IP versus IIP procedures showed that the former scored worse in 4 out of 5 parameters analyzed. Conclusion. IIP procedures produce less postoperative discomfort. IIP procedures, namely, orthognathic surgery, should be the first choice intervention in patients affected by OSAS and dentoskeletal malformation. [ABSTRACT FROM AUTHOR]

In this article, a self-contained procedure to estimate the vertical, medial–lateral, and anterior–posterior displacement of a single sacrum-worn inertial measurement unit (IMU) is presented, which can be related to the human body center of mass (CoM) displacement during treadmill walking through an adaptation of the sacral marker method. Furthermore, a magnetometer-free custom sensor-fusion algorithm for orientation estimation is proposed alongside a practical alignment procedure to refer relative IMU orientation estimation to a ground-fixed reference frame. Twelve healthy subjects performed two trials of treadmill walking at 3, 4, and 5 km/h for 150 s, with a sacrum-worn IMU. Orientation and displacement estimations were then compared with those obtained from an optoelectronic measurement system. Roll, pitch, and yaw angles showed root mean square error (RMSE) lower than 2° for walking trials at 3, 4, and 5 km/h, with Pearson’s correlation coefficient higher than 0.90 for each angle. Displacement accuracy was evaluated in terms of peak-to-trough distances and RMSE. Mean errors resulted lower than 1 mm for each axis of interest and for each gait speed, with RMSE not higher than 2.5 mm. The proposed off-line algorithm can be used in low-budget and infrastructure-free environments, to achieve reliable CoM displacement estimation during cyclic activities such as treadmill walking. [ABSTRACT FROM AUTHOR]

The use of anaesthetic drugs in the treatment of oral aphthosis is one of the pharmaceutical possibilities that a doctor can use for the most painful forms. Normally, Lidocaine or Diclofenac is used to treat this disease, but they can be used for a very limited time and so they are of little practical use. In this study, the authors have used Ropivacaine whose pharmaceutical kinetics allows the analgesic effect to be active for 60 to 90 minutes. In our research, we compared 8 groups of patients who have been given 3 principal pharmaceutical products: one group was given an anaesthetic drug, one had a topical medication administered which is often used for the treatment of aphthous lesions, and the last group was given a multivitamin. These pharmaceutical products were used alone and in various possible combinations in the 8 groups. The results of this study are very interesting and show that in all the groups that used anaesthetics there was more satisfaction on the patients' part because their pain level became more manageable right after the first application of the drug and the patients could carry on with their normal lives. [ABSTRACT FROM AUTHOR]

For the assessment of glucose tolerance from IVGTT data in Zucker rat, minimal model methodology is reliable but time- and money-consuming. This study aimed to validate for the first time in Zucker rat, simple surrogate indexes of insulin sensitivity and secretion against the glucose-minimal-model insulin sensitivity index (SI) and against first- (Φ1) and second-phase (Φ2) β-cell responsiveness indexes provided by C-peptide minimal model. Validation of the surrogate insulin sensitivity index (ISI) and of two sets of coupled insulin-based indexes for insulin secretion, differing from the cut-off point between phases (FPIR3-SPIR3, t = 3 min and FPIR5-SPIR5, t = 5 min), was carried out in a population of ten Zucker fatty rats (ZFR) and ten Zucker lean rats (ZLR). Considering the whole rat population (ZLR+ZFR), ISI showed a significant strong correlation with SI (Spearman’s correlation coefficient, r = 0.88; P<0.001). Both FPIR3 and FPIR5 showed a significant (P<0.001) strong correlation with Φ1 (r = 0.76 and r = 0.75, respectively). Both SPIR3 and SPIR5 showed a significant (P<0.001) strong correlation with Φ2 (r = 0.85 and r = 0.83, respectively). ISI is able to detect (P<0.001) the well-recognized reduction in insulin sensitivity in ZFRs, compared to ZLRs. The insulin-based indexes of insulin secretion are able to detect in ZFRs (P<0.001) the compensatory increase of first- and second-phase secretion, associated to the insulin-resistant state. The ability of the surrogate indexes in describing glucose tolerance in the ZFRs was confirmed by the Disposition Index analysis. The model-based validation performed in the present study supports the utilization of low-cost, insulin-based indexes for the assessment of glucose tolerance in Zucker rat, reliable animal model of human metabolic syndrome. [ABSTRACT FROM AUTHOR]

Objectives To develop a comparative, cost-effectiveness, and budget impact analysis of Therakos online extracorporeal photopheresis (ECP) compared with the main alternatives used for the treatment of steroid-refractory/resistant chronic graft-versus-host disease (cGvHD) in Italy. Methods The current therapeutic pathway was identified by searching medical databases and from the results of a survey of practice in Italian clinical reference centers. A systematic review was performed to evaluate the efficacy and safety of second-line alternatives. Budget impact and cost-effectiveness analyses were performed from the Italian National Health Service perspective over a 7-year time horizon through the adaption of a Markov model. The following health states were considered: complete and partial response, stable disease, and progression. A discount rate of 3% was applied to costs and outcomes. Results The most common alternatives used in Italy for the management of steroid-refractory/resistant cGvHD were ECP, mycophenolate, pentostatin, and imatinib. The literature review highlighted that complete and partial responses are higher with ECP than with the alternatives while serious adverse events are less common. The economic analysis showed that Therakos online ECP represents the dominating alternative, in that it delivers greater benefit at a lower cost. In fact, according to the alternatives considered, cost saving ranged from €3237.09 to €19,903.51 per patient with 0.04 to 0.21 quality-adjusted life-year gained. Conclusions Therakos online ECP should be considered an effective, safe, and cost-effective alternative in steroid-refractory/resistant cGvHD. There is inequality in access, and a dedicated reimbursement tariff, however, should be introduced to overcome these barriers. [ABSTRACT FROM AUTHOR]

Objective. Systemic lupus erythematosus (SLE) is treated with anti-inflammatory and immunosuppressive drugs and off-label biologics. Belimumab is the first biologic approved after 50 years as an add-on therapy for active disease. This paper summarizes a health technology assessment performed in Italy. Methods. SLE epidemiology and burden were assessed using the best published international and national evidences and efficacy and safety of belimumab were synthesized using clinical data. A cost-effectiveness analysis was performed by a lifetime microsimulation model comparing belimumab to standard of care (SoC). Organizational and ethical implications were discussed. Results. Literature review showed that SLE affects 47 per 100,000 people for a total of 28,500 patients in Italy, 50% of whom are affected by active form of the disease despite SoC. These patients, if autoantibodies and anti-dsDNA positive with low complement, are eligible for belimumab. SLE determines work disability and a 2-5-fold increase inmortality. Belimumab with SoCmay prevent 4,742 flares in three years being cost-effective with an incremental costeffectiveness ratio of C32,859 per quality adjusted life year gained. From the organizational perspective, the development of clear and comprehensive clinical pathways is crucial. Conclusions. The assessment supports the use of belimumab into the SLE treatment paradigm in Italy. [ABSTRACT FROM AUTHOR]

Somatosympathetic reflexes were studied in young hyperinsulinemic, insulin-resistant (Zucker fatty) rats (ZFR) and a related control (Zucker lean) strain (ZLR). Glucose metabolism was characterized by minimal model analysis of intravenous glucose tolerance test data. Seven-week-old ZFR (n = 18) and ZLR (n = 17) were studied under pentobarbital anesthesia. Mean body weight and plasma glucose and insulin concentration were significantly greater (P < 0.05) in ZFR than in ZLR, whereas basal values of mean arterial pressure (MAP) and heart rate (HR) were not significantly different. Increments of MAP (ΔMAP) and HR (AHR) elicited by electrical stimulation of the sciatic nerve (5-s trains of 100 pulses, 0.5-ms pulse duration, 100- to 400-μA pulse intensity) were significantly higher (ANOVA, P < 0.05) in ZFR at each level of stimulus intensity. Regression analysis showed a linear increase in ΔMAP and AHR with increasing sciatic nerve stimulus intensity. Pressor responses to phenylephrine after ganglionic blockade demonstrated that vascular reactivity to adrenergic stimulation is not increased in ZFR compared with ZLR. Thus this factor does not contribute to enhancement of somatosympathetic reflexes observed in this strain. Insulin sensitivity in ZFR was one-fourth (P < 0.05) that in ZLR. These results suggest that stronger sympathetic nervous reactivity in ZFR is associated with a severe insulin-resistant state before the onset of hypertension and support the hypothesis that insulin-mediated stimulation of the sympathetic nervous system is involved in the development of cardiovascular diseases related to alterations of glucose metabolism. [ABSTRACT FROM AUTHOR]