Rilpivirine plus cobicistat-boosted darunavir as a two-drug switch regimen in HIV-infected, virologically suppressed subjects on steady standard three-drug therapy: a randomized, controlled, non-inferiority trial (PROBE 2).

BACKGROUND: We explored the combination of rilpivirine plus cobicistat-boosted darunavir [a two-drug regimen (2DR)] when switching from standard triple combined ART. METHODS: In this randomized, open-label, non-inferiority trial, participants had an HIV-RNA <50 copies/mL on a stable (>6 months) three-drug regimen. The primary endpoint was proportion with HIV-RNA <50 copies/mL at Week 24 (snapshot algorithm), with a -12% non-inferiority margin. ClinicalTrials.gov: NCT04064632. RESULTS: One hundred and sixty patients were allocated (1:1) to 2DR or to continue current ART (CAR). At Week 24, 72 (90.0%) of participants with 2DR and 75 (93.8%) with CAR maintained HIV-RNA <50 copies/mL [difference -3.75% (95% CI = -11.63 to 5.63)], confirming non-inferiority. Non-inferiority was confirmed considering an HIV-RNA >50 copies/mL (0% for 2DR; 3.7% for CAR; 95% CI = -0.4 to 7.9). Four patients reported adverse events not leading to treatment discontinuation (one patient in the 2DR group and three patients in the CAR group); eight subjects discontinued therapy in the 2DR group and three in the CAR group. With 2DR, lipid serum concentrations increased, but differences were statistically significant only for tenofovir disoproxil fumarate-containing CAR and in 2DR patients receiving a pre-switch regimen including tenofovir disoproxil fumarate. Median bone stiffness decreased in the CAR group from 86.1 g/cm2 (IQR = 74-98) to 83.2 g/cm2 (IQR = 74-97) and increased in the 2DR group from 84.9 g/cm2 (IQR = 74-103) to 85.5 g/cm2 (IQR = 74-101). The reduction within the CAR group was significant (P = 0.043). CONCLUSIONS: Once-daily rilpivirine plus cobicistat-boosted darunavir is an effective 2DR that combines a high virological efficacy with a potential to avoid major NRTI toxicities.

Valorization of clinical trials from the Italian National Health Service perspective: definition and first application of a model to estimate avoided costs.

Introduction: From the perspective of healthcare organizations and public health care systems, the value of a clinical trial can be assessed from a clinical and economical perspective. However, to date, there is no standardized model for systematically capturing the economic value of clinical trials at organizational and system levels. The aim of this study was to develop and test a methodology for estimating the avoided costs deriving from the management of patients as part of a clinical trial. Methods: Our methodology is based on the assumption that the economic value of a clinical trial derives from 1) the funding received by the experimental site from a trial's sponsor, and from 2) the cost avoided by the experimental site with the treatment of patients within a study and not according to standard care by the experimental site. Results: By applying the methodology to onco-hematological clinical trials conducted in two academic hospitals from 2011 to 2016, we demonstrate that savings between 2 million and 4 million euros were achieved over a five-year period. Thus, for every 1,000 euros invested by the pharmaceutical company into the clinical studies conducted at these hospitals, the hospitals saved on average 2,200 euros due to costs not incurred as a result of the trials. Conclusions: The study has proposed and tested a methodology for estimating the economic value of clinical trials by taking into account avoided costs deriving from the treatment of patients enrolled in sponsored trials. The study has proposed a management tool for healthcare institutions to govern clinical trials.

Hematological complications in anorexia nervosa.

BACKGROUND/OBJECTIVES: Anemia, leukopenia and, although less frequently, thrombocytopenia are possible hematological complications of anorexia nervosa considered strictly secondary to chronic malnutrition. This is a retrospective study on the prevalence of these disorders in a large cohort of 318 female patients with AN (20.4±5.6 years, body mass index (BMI) 15.9±1.6 kg/m2), recruited in the Outpatient Unit for Malnutrition secondary to Eating Disorders at the Department of Clinical Medicine and Surgery, Federico II University Hospital, since February 1991 to December 2012. SUBJECTS/METHODS: Patients were studied on an outpatient basis after obtaining medical history, clinical examination, routine hematobiochemical and endocrine tests, electrocardiography, psychiatric interview and bioelectrical impedance analysis and, in particular, phase angle determination. All patients with other comorbidities, in particular with mean corpuscular volume <80 fl, were excluded for suspected genetic alteration in the synthesis of hemoglobin. RESULTS: Hematologic data showed that 16.7% of patients had anemia, 7.9% neutropenia and 8.9% thrombocytopenia. These abnormalities were strictly related to the duration of illness (P=0.028), and to protein energy malnutrition, in particular, BMI and phase angle (P<0.001). CONCLUSIONS: Our study offers description of the incidence of hematologic defects in a selected and large sample of AN female patients, suggesting that its incidence is related to the degree and duration of protein energy malnutrition.

Effect of phytochemical concentrations on biological activities of cranberry extracts.

Plants of cranberry (Vaccinium macrocarpon) furnish edible fruits and derivates that have been used for the prevention and treatment of urinary tract infections. In the present work we compare two commercial extracts that contain proanthocyanins (PACs) at 4 percent and 20 percent for antimicrobial, antiproliferative, antiradical and protective properties against oxidative stress on cell lines. Both extracts showed antimicrobial activity (MIC values range 3-100 microg/ml). Extract at 20 percent PACs showed higher antiproliferative activity against HepG2 and MCF7 cells, but not against C2C12 cells. Both extracts showed a dose-dependent free-radical scavenging capacity, and a protective effect on the cell damage was also revealed by reduction of intracellular active oxygen species release. Cranberry extracts confirmed antioxidative properties and efficacy in reduction of cell viability that resulted stronger against tumor cells. The pretreatment with cranberry extracts, furthermore, reveal an increase of cell resistance against oxidative stress, suggesting a potential role as a dietary supplement in preventing free-radical damage. The proanthocyanidin content is critical to determine the extract efficacy. In cellular experiments the extracts resulted clearly differentiated in their activity, and the activity was strongly influenced by PACs content. Only in DPPH test the free radical scavenging activity seemed to be directly related to proanthocyanidins content.

Monitoring prion protein expression in complex biological samples by SERS for diagnostic applications.

Surface-enhanced Raman spectroscopy (SERS) allows a new insight into the analysis of cell physiology. In this work, the difficulty of producing suitable substrates that, besides permitting the amplification of the Raman signal, do not interact with the biological material causing alteration, has been overcome by a combined method of hydrothermal green synthesis and thermal annealing. The SERS analysis of the cell membrane has been performed with special attention to the cellular prion protein PrP(C). In addition, SERS has also been used to reveal the prion protein-Cu(II) interaction in four different cell models (B104, SH-SY5Y, GN11, HeLa), expressing PrP(C) at different levels. A significant implication of the current work consists of the intriguing possibility of revealing and quantifying prion protein expression in complex biological samples by a cheap SERS-based method, replacing the expensive and time-consuming immuno-assay systems commonly employed.

Non-functionalized silver nanoparticles for a localized surface plasmon resonance-based glucose sensor.

The optical properties of non-functionalized silver nanoparticles in ethanol solution have been analyzed and a progressive shift of localized surface plasmon resonances caused by the adding of increasing quantities of glucose has been observed. To understand this occurrence, the interaction of glucose molecules with the silver nanoparticle surface has been investigated using Raman spectroscopy. In addition, high resolution transmission electron microscopy shows the presence of superstructures on the silver nanoparticle surface that can be imputed to the presence of glucose.

Isospin dependence of incomplete fusion reactions at 25 MeV/nucleon.

40Ca+;{40,48}Ca,46Ti reactions at 25 MeV/nucleon have been studied using the 4pi CHIMERA detector. An isospin effect on the competition between fusionlike and binarylike reaction mechanisms has been observed. The probability of producing a heavy residue is lower in the case of N approximately Z colliding systems as compared to the case of reactions induced on the neutron rich 48Ca target. Predictions based on constrained molecular dynamics II calculations show that the competition between fusionlike and binary reactions in the selected centrality bins can constrain the parametrization of the symmetry energy and its density dependence in the nuclear equation of state.

Bioelectrical impedance phase angle in constitutionally lean females, ballet dancers and patients with anorexia nervosa.

BACKGROUND/OBJECTIVE: Several articles have described body composition in anorexia nervosa, whereas little is known about this issue in underweight ballet dancers and constitutionally lean females. The main aim of this study was to assess whether phase angle (a bioimpedance variable related to body cell mass) differs according to the type of underweight in female adolescents and young women. SUBJECTS/METHODS: Skinfold thicknesses and bioimpedance analysis (whole body and limbs) were evaluated in three groups of underweight patients (30 patients with anorexia nervosa, 10 constitutionally lean individuals and 15 classical dancers) and 30 normal weight controls. RESULTS: There were no differences between the three groups of underweight patients with respect to anthropometric and bioelectrical impedance analysis (BIA) variables with the exception of phase angle. The latter was significantly higher in dancers, lower in anorectic patients and not different in constitutionally lean patients, as compared with controls. CONCLUSIONS: Phase angle (assessed by single-frequency BIA) appears to discriminate between different forms of underweight, being an effective marker of qualitative changes in body composition.

A new amperometric nanostructured sensor for the analytical determination of hydrogen peroxide.

A new amperometric, nanostructured sensor for the analytical determination of hydrogen peroxide is proposed. This sensor was constructed by immobilizing silver nanoparticles in a polyvinyl alcohol (PVA) film on a platinum electrode, which was performed by direct drop-casting silver nanoparticles that were capped in a PVA colloidal suspension. UV-vis spectroscopy, X-ray diffraction and transmission electron microscopy were used to give a complete characterization of the nanostructured film. Cyclic voltammetry experiments yielded evidence that silver nanoparticles facilitate hydrogen peroxide reduction, showing excellent catalytic activity. Moreover, the cronoamperometric response of modified sensors was dependent on nanoparticle lifetime. Experiments were performed, using freshly prepared solutions, after 4 and 8 days. Results concerning the quantitative analysis of hydrogen peroxide, in terms of detection limit, linear range, sensitivity and standard deviation (STD), are discussed for each tested sensor type. Utilization of two different linear ranges (40 microM to 6mM and 1.25 microM to 1.0mM) enabled the assessment of concentration intervals having up to three orders of magnitude. Moreover, the electrode made using a 4-day-old solution showed the maximal sensitivity of 128 nA microM(-1)(4090 nA microM(-1)cm(-2)), yielding a limit of detection of 1 microuM and STD of 2.5 microAmM(-1). All of these analytical parameters make the constructed sensors suitable for peroxide determination in aqueous solution.

Fast ternary and quaternary breakup of the 197Au + 197Au system in collisions at 15 MeV/nucleon.

A new reaction mechanism of violent reseparation of a heavy nucleus-nucleus system, 197Au + 197Au, into three or four massive fragments in collisions at 15 MeV/nucleon has been observed. After reseparation, the fragments are almost exactly aligned, thus showing a very short time scale of the reseparation process, of about 70-80 fm/c.

Long-term mortality in anorexia nervosa: a report after an 8-year follow-up and a review of the most recent literature.

OBJECTIVE: To evaluate long-term mortality rate of anorexia nervosa (AN) patients in a southern Italy population compared to the most recent literature. DESIGN: Retrospective and review setting. PATIENTS AND INTERVENTIONS: One hundred and forty-seven female AN patients, consecutively admitted from 1994 to 1997 to the Outpatient Unit, were re-examined between June and November 2003. Our data are compared with 10 other studies published since 1988. RESULTS: One hundred and twenty-three deaths in 2240 patients, amounting to a total mortality rate of 5.25% were reported in the literature. Deaths due to suicide, AN-related and AN-unrelated diseases were 1.20, 3.07 and 0.98%, respectively. After correcting for unrelated deaths, mortality rate was 4.27%. In our 8-year follow-up, we found a mortality rate of 2.72% (1.82% after correcting for unrelated deaths). Standardized mortality ratio was 9.7. CONCLUSION: We interpret our favourable findings as a consequence of an integrated, clinical-nutritional and psychiatric approach. Finally, considering AN demographic characteristics, that is young female subjects in Westernized societies, mortality rate is confirmed to be dramatically high.

Integrated medical-psychiatric treatment of the "crisis phase" in severe protein-energy malnutrition secondary to major eating disorders.

C.A., a 23-year old male was admitted in the clinical nutrition medical ward for severe, complicated protein-energy malnutrition (PEM) [body mass index (BMI) 11.08 kg/m2; body weight kg 35.81 due to major eating disorders. C.A.'s personality was narcissistic, with a rigid psychic structure. During hospitalitation (lasted 72 days) two acute episodes (a possibly self-inflicted damage and a persecution feeling) occurred that we consider as part of the "crisis phase", the period in which the patient's restrictive behaviour is no longer able to keep his personality equilibrium stable. The patient was treated by an integrated medical and psychiatric approach, including periods of never forced parenteral nutrition, nutritional and intensive psychoterapeutic interventions. For a short period the patient received also a pharmacological support (aloperidol orally). Treatment was successful and the patient was discharged completely autonomous and followed up on an outpatient basis. After about one year follow-up he is still in good clinical condition and in sufficient psychological equilibrium.

Comparison of bioelectrical impedance analysis and dual-energy X-ray absorptiometry for the assessment of appendicular body composition in anorexic women.

OBJECTIVE: To establish the accuracy of bioelectrical impedance analysis (BIA) for the assessment of appendicular body composition in anorexic women. DESIGN: Cross-sectional study. SETTING: Outpatient University Clinic. SUBJECTS: A total of 39 anorexic and 25 control women with a mean (s.d.) age of 21 (3) y. METHODS: Total, arm and leg fat-free mass (FFM) were measured by dual-energy X-ray absorptiometry and predicted from total and segmental BIA at 50 kHz. The predictor variable was the resistance index (Rl), that is, the ratio of height (2) to body resistance for the whole body and the ratio of length(2)/limb resistance for the arm and leg. RESULTS: Predictive equations developed on controls overestimated total, arm and leg FFM in anorexics (P<0.0001). Population-specific equations gave a satisfactory estimate of total and appendicular FFM in anorexics (P=NS) but had higher percent root mean square errors (RMSEs%) as compared to those developed on controls (8% vs 5% for whole body, 12% vs 10% for arm and 10% vs 8% for leg). The accuracy of the estimate of total and leg FFM in anorexics was improved by adding body weight (Wt) as a predictor with Rl (RMSE%=5% vs 8% and 7% vs 10%, respectively). However, the same accuracy was obtained using Wt alone, suggesting that in anorexics, BIA at 50 kHz is not superior to Wt for assessing total and leg FFM. CONCLUSION: BIA shows some potential for the assessment of appendicular body composition in anorexic women. However, Wt is preferable to BIA at 50 kHz on practical grounds. Further studies should consider whether frequencies >50 kHz give better estimates of appendicular composition in anorexics as compared to Wt. SPONSORSHIP: University of Napoli.

Outcome predictors in the short-term treatment of anorexia nervosa: an integrated medical-psychiatric approach.

OBJECTIVES: Factors predicting clinical outcome in the short-term treatment of anorexia nervosa. DESIGN: Longitudinal follow-up study. SETTING: Department of Clinical and Experimental Medicine, "Federico II" University of Naples. PARTICIPANTS: Fifty-eight young anorectic women consecutively attending the outpatient Unit between January 1997 and December 2000. MAIN OUTCOME MEASURES: Body weight changes over six months' follow-up. RESULTS: Body weight changes in the short term was exclusively predicted by the prevalent underlying psychiatric disorder, being increased in the patients with prevalently depressive traits, decreased in those with psychotic features and unchanged in those with a prevalently narcissistic personality. CONCLUSIONS: The prevalent psychiatric disorder seems to predict clinical outcome in the short term. Body weight gain per se cannot always be the main target of medical intervention, at least in the early phase of the treatment of malnutrition secondary to major eating disorders.

Are the general equations to predict BMR applicable to patients with anorexia nervosa?

AIM: To determine whether the general equations to predict basal metabolic rate (BMR) can be reliably applied to female anorectics. INDIVIDUALS AND METHODS: Two hundred and thirty-seven female patients with anorexia nervosa (AN) were divided into an adolescent group [n=43, 13-17 yrs, 39.3+/-5.0 kg, body mass index (BMI) (weight/height) 15.5+/-1.8 kg/m2] and a young-adult group (n=194, 18-40 yrs, 40.5+/-6.1 kg, BMI 15.6+/-1.9 kg/m2). BMR values determined by indirect calorimetry were compared with those predicted according to either the WHO/FAO/UNU or the Harris-Benedict general equations, or using the Schebendach correction formula (proposed for adjusting the Harris-Benedict estimates in anorectics). RESULTS: Measured BMR was 3,658+/-665 kJ/day in the adolescent and 3,907+/-760 kJ/day in the young-adult patients. In the adolescent group, the differences between predicted and measured values were (mean+/-SD) 1,466 529 kJ/day (+44+/-21%) for WHO/FAO/UNU, 1,587+/-552 kJ/day (+47+/-23%) for the Harris-Benedict and -20+/-510 kJ/day for the Schebendach (+1+/-13%), while in the young-adult group the corresponding values were 696+/-570 kJ/day (+24+/-24%), 1,252+/-644 kJ/day (+37+/-27%) and -430+/-640 kJ/day (-9+/-16%). The bias was negatively associated with weight and BMI in both groups when using the WHO/FAO/UNU and Harris-Benedict equations, and with age in the young-adult group for the Harris-Benedict and Schebendach equations. CONCLUSIONS: The WHO/FAO/UNU and Harris-Benedict equations greatly overestimate BMR in AN. Accurate estimation is to some extent dependent on individual characteristics such as age, weight or BMI. The Schebendach correction formula accurately predicts BMR in female adolescents, but not in young adult women with AN.

Possibility to deduce the emission time sequence of neutrons and protons from the neutron-proton correlation function.

Experimental information has been derived from the neutron-proton correlation function in order to deduce the time sequence of neutrons and protons emitted at 45 degrees in the E/A = 45 MeV 58Ni + 27Al reaction.

The prediction of basal metabolic rate in female patients with anorexia nervosa.

OBJECTIVE: To evaluate in female patients with anorexia nervosa the accuracy of a specific predictive formula for basal metabolic rate (BMR) already proposed in the literature and to derive a new disease-specific equation with the same purpose. DESIGN: Cross-sectional study. SUBJECTS: One-hundred and twenty adolescent girls (<18 y) and young-adult women (18-30 y) with anorexia nervosa. MEASUREMENTS: BMR was determined by indirect calorimetry or predicted according to the Schebendach formula, which was specifically derived for anorexia nervosa. RESULTS: On average the Schebendach formula performed well in the adolescent group but not in the young-adult group. The range including 95% of the predicted-measured differences was in both cases wider than 2000 kJ/day. In the young-adult patients the accuracy of the prediction was also related to age and body mass index. Weight and age (but not height or body mass index) emerged as predictors of BMR in the sample as a whole, and only weight when the two age groups were considered separately, thus leading to three different equations. The intercepts of these regression lines were very close and not significantly different from zero while their standard error of estimate was 500-550 kJ/day. CONCLUSION: The Schebendach formula is not very accurate in estimating the BMR of female anorectic patients. Moreover, in this group the relationship between BMR and weight was altered. The predictive formulas proposed by the present study have a reasonable prediction power.