The direct and indirect cost of diabetes in Italy: a prevalence probabilistic approach.

INTRODUCTION: Diabetes mellitus is a chronic degenerative disease associated with a high risk of chronic complications and comorbidities. However, very few data are available on the associated cost. The objective of this study is to identify the available information on the epidemiology of the disease and estimate the average annual cost incurred by the National Health Service and Society for the Treatment of Diabetes in Italy. METHODS: A probabilistic prevalence cost of illness model was developed to calculate an aggregate measure of the economic burden associated with the disease, in terms of direct medical costs (drugs, hospitalizations, monitoring and adverse events) and indirect costs (absenteeism and early retirement). A systematic review of the literature was conducted to determine both the epidemiological and economic data. Furthermore, a one-way and probabilistic sensitivity analysis with 5,000 Monte Carlo simulations was performed to test the robustness of the results and define a 95% CI. RESULTS: The model estimated a prevalence of 2.6 million patients under drug therapies in Italy. The total economic burden of diabetic patients in Italy amounted to €20.3 billion/year (95% CI €18.61 to €22.29 billion), 54% of which are associated with indirect costs (95% CI €10.10 to €11.62 billion) and 46% with direct costs only (95% CI €8.11 to €11.06 billion). CONCLUSIONS: This is the first study conducted in Italy aimed at estimating the direct and indirect cost of diabetes with a probabilistic prevalence approach. As might be expected, the lack of information means that the real burden of diabetes is partly underestimated, especially with regard to indirect costs. However, this is a useful approach for policy makers to understand the economic implications of diabetes treatment in Italy.

Interplay between Raman and polarization effects in next-generation passive optical networks.

In this paper, we study in details some Raman-induced impairments that arise in Next-Generation Passive Optical Networks (NG-PON2) in a full coexistence scenario between GPON and TWDM-PON. The main new contribution of this paper is to take into account the polarization launches of the different signals at the transmitter, in order to find the best polarization arrangement. We found that launching the TWDM-PON wavelengths on alternately orthogonal polarization minimizes the Raman depletion effect on GPON over all possible PMD values, thus resulting in the optimal polarization launching condition, while any other polarization launch has a higher out of service probability for realistic PMD values.

Antiretroviral treatment-based cost saving interventions may offset expenses for new patients and earlier treatment start.

OBJECTIVES: Combination antiretroviral therapy (cART) has become the main driver of total costs of caring for persons living with HIV (PLHIV). The present study estimated the short/medium-term cost trends in response to the recent evolution of national guidelines and regional therapeutic protocols for cART in Italy. METHODS: We developed a deterministic mathematical model that was calibrated using epidemic data for Lazio, a region located in central Italy with about six million inhabitants. RESULTS: In the Base Case Scenario, the estimated number of PLHIV in the Lazio region increased over the period 2012-2016 from 14 414 to 17 179. Over the same period, the average projected annual cost for treating the HIV-infected population was €147.0 million. An earlier cART initiation resulted in a rise of 2.3% in the average estimated annual cost, whereas an increase from 27% to 50% in the proportion of naïve subjects starting cART with a nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimen resulted in a reduction of 0.3%. Simplification strategies based on NNRTIs co-formulated in a single tablet regimen and protease inhibitor/ritonavir-boosted monotherapy produced an overall reduction in average annual costs of 1.5%. A further average saving of 3.3% resulted from the introduction of generic antiretroviral drugs. CONCLUSIONS: In the medium term, cost saving interventions could finance the increase in costs resulting from the inertial growth in the number of patients requiring treatment and from the earlier treatment initiation recommended in recent guidelines.

Autocorrelation of the polarization-dependent loss in fiber routes.

We study the spectral properties of polarization-dependent loss (PDL) in fiber routes with multiple spans and amplifiers. In these systems, PDL stems from a small number of lumped WDM components interconnected by PDL-free fibers, a configuration that is poorly described by the popular model of distributed PDL. We derive transparent and practical analytical expressions for the autocorrelation functions of the PDL vector and of the square PDL magnitude and show that they are strongly affected by the order of the individual PDL elements.

Intrachannel nonlinearity enhancement in polarization multiplexed phase modulated systems with differential detection.

We compare nonlinear impairments in phase-modulated transmission with and without polarization multiplexing. Using an analytic approach that enabled us to accurately predict the Q factor at the receiver, we show that, without polarization multiplexing, the differential receiver is insensitive to two-pulse cross phase modulation, whereas with polarization multiplexing two-pulse interaction between cross-polarized components causes significant performance degradation.

Intra-channel nonlinearity in differentially phase-modulated transmission.

The mechanisms responsible for nonlinear impairments in single-channel phase modulated system employing differential detection are investigated. The role of dispersion precompensation is discussed. It is shown that precompensation may be designed as to minimize the in-phase components of the fluctuations thus reducing nonlinear impairments. In differential-phase-shift-keying the effect of precompensation is stronger than in differential-quadrature-phase-shift-keying. The results of an analytic theory are compared with split-step based computer simulations using realistic system parameters.

A population-based study of acute stroke and TIA diagnosis.

BACKGROUND: Acute stroke therapy is heavily dependent on the diagnostic acumen of the physician in the emergency department (ED). OBJECTIVE: To determine this diagnostic accuracy in a population-based multiethnic stroke study. METHODS: The Brain Attack Surveillance in Corpus Christi (BASIC) Project prospectively ascertained all acute stroke or TIA cases in an urban Texas county of 313,645 residents without an academic medical center. Cases were validated by board-certified neurologists using source documentation. Case validation was used as the gold standard to compare the diagnosis given by the ED physician. RESULTS: From January 2000 to August 2002, a total of 13,015 patients were screened. Of these, 1,800 were validated as stroke/TIA. Overall sensitivity of the emergency physician for the BASIC-validated diagnosis was 92%, and positive predictive value was 89%. Of the cases that the emergency physician thought were stroke, 11% were validated as no stroke. In multivariable modeling, motor symptoms was an independent predictor of protection from false-negative ED diagnosis of stroke/TIA (odds ratio [OR] = 0.61; 95% CI 0.41 to 0.89). Protection from false-positive stroke/TIA diagnosis was predicted by sensory symptoms (OR = 0.43; 95% CI 0.28 to 0.66), motor symptoms (OR = 0.44; 95% CI 0.32 to 0.62), and severe neurologic deficit (OR = 0.33; 95% CI 0.14 to 0.78). History of stroke/TIA predicted false-positive stroke diagnosis (OR = 1.72; 95% CI 1.23 to 2.40). The majority of disagreements occurred in patients with generalized neurologic or acute medical, nonneurologic syndromes. CONCLUSIONS: Physicians practicing in the ED are sensitive for stroke/TIA diagnosis. The modest positive predictive value argues for a systems approach with neurology support so that proper decisions regarding acute stroke therapy can be made.

Flow cytometric DNA ploidy, p53, PCNA, and c-erbB-2 protein expressions as predictors of survival in surgically resected gastric cancer patients.

In order to determine retrospectively the impact of some cytometric and immunohistochemical parameters on the overall survival of gastric cancer patients treated with surgery alone, paraffin-embedded tumor samples from 137 gastric carcinoma patients undergoing curative resection from 1987-1993 were analyzed by flow cytometry (FCM) and immunohistochemistry (p53, c-erbB-2, and PCNA expression). FCM-derived parameters were DNA ploidy and fraction of S-phase cells (SPF). Multiple regression analysis was applied to determine the prognostic significance of the conventional clinicopathologic findings together with the flow cytometric and immunohistochemical parameters on overall survival. When all parameters were entered simultaneously into the Cox regression model, stage and DNA ploidy (DNA index >1.35) clearly emerged as the only independent prognostic factors. When the stages were analysed separately, the independent prognostic factors resulted DNA ploidy in early stages (I-II) and grading in stage IIIA tumors. For stage IIIB tumors, no independent prognostic factor was found. These results indicate that the DNA ploidy pattern is a valuable predictor of survival in curatively resected gastric cancer patients, especially when less advanced tumors are taken into consideration.

Study of the frequency autocorrelation of the differential group delay in fibers with polarization mode dispersion.

We study the frequency autocorrelation of the differential group delay (DGD) in fibers with polarization mode dispersion (PMD). We show that the correlation bandwidth of the DGD is comparable with that of the orientation of the PMD vector. Furthermore, we show that all the most general statistical properties of polarization mode dispersion in long fibers are uniquely determined by the mean DGD. An estimate of the accuracy of measurements in which the mean DGD is extracted by frequency averaging in a single fiber is obtained as a function of the measured bandwidth.

Bit rate and pulse width dependence of four-wave mixing of short optical pulses in semiconductor optical amplifiers.

We investigate the saturation properties of four-wave mixing of short optical pulses in a semiconductor optical amplifier. By varying the gain of the optical amplifier, we find a strong dependence of both conversion efficiency and signal-to-background ratio on pulse width and bit rate. In particular, the signal-to-background ratio can be optimized for a specific amplifier gain. This behavior, which is coherently described in experiment and theory, is attributed to the dynamics of the amplified spontaneous emission, which is the main source of noise in a semiconductor optical amplifier.

Combined hyperfractionated radiotherapy and protracted infusion chemotherapy in bladder cancer for organ preservation.

PURPOSE: To test an innovative schedule of concurrent protracted intravenous infusion (PVI) of cisplatin (CDDP) and 5-fluorouracil (5-FU) and hyperfractionated radiotherapy (HFRT) with organ-sparing intent in bladder cancer. PATIENTS AND METHODS: Fifty-two patients (pts) were selected to receive an aggressive TURB followed by 2 MCV cycles, and HFRT with concomitant CDDP and 5-FU PVI (33 pts) or HFRT and concomitant CDDP and 5-FU PVI (20 pts). The 5-FU and CDDP doses ranged from 180 to 220 mg/sm/day and from 4 to 6 mg/sm/day, respectively. Radiotherapy was delivered as three 100 cGy fraction per day or two 150 cGy fraction per day to a total dose of 50 Gy to the pelvis and a 20 Gy boost to the bladder. RESULTS: Grade III toxicity in pts who received or not MCV was: rectal tenesmus 12/33 and 0/20, dysuria 6/33 and 4/20, leukopenia 3/33 and 0/20, thrombocytopenia 7/33 and 1/20 pts, respectively. A Grade IV toxicity was observed in 2 pts. Of the 28 evaluable patients treated with MCV, CR were observed in 23 (82%) and PR in 5 cases. Of the 18 evaluable patients treated without MCV, CR were observed in 18 cases (100%). Actually, 65% and 14% of the CR pts treated with or without HCV are alive and free of tumor. CONCLUSIONS: This bladder-sparing treatment shows an acceptable acute and late toxicity, similar to that observed with radiotherapy alone. The high CRs and bladder preservation rates observed deserve further clinical evaluation.

Combined treatment of invasive bladder carcinoma with transurethral resection, induction chemotherapy, and radical radiotherapy plus concomitant protracted infusion of cisplatin and 5-fluorouracil: a phase I study.

BACKGROUND: The aim of this study was to define the maximum tolerated doses (MTDs) of cisplatin (CDDP) and 5-fluorouracil (5-FU) administered as protracted intravenous infusion (PVI) during hyperfractionated radiotherapy (HFRT) administered with organ-sparing intent to patients with infiltrating transitional cell carcinoma of the bladder (TCCB). METHODS: Twenty-five patients with T2-T4aNXM0 TCCB were enrolled in this study. After a complete transurethral resection, bladder mapping, and two cycles of induction chemotherapy, patients were submitted to HFRT and CDDP + 5-FU as concomitant PVI at escalating dose levels until MTDs were reached. Treatment efficacy was also evaluated, in terms of complete response (CR) rates and cystectomy free, disease free, and overall survival. RESULTS: Combined treatment was well tolerated. The recommended doses for Phase II studies of PVI chemotherapy and radiotherapy for patients with invasive bladder carcinoma are CDDP 5 mg/m2/day and 5-FU 220 mg/m2/day. Twenty-four patients were evaluable for response: 21 (87.5%) had CR and 3 PR. After a median follow-up of 31 months (range, 11-49 months), 18 of 21 patients with CRs (86%) were alive: 15 (71.4%) had tumor free bladder, of whom 3 had superficial recurrence successfully treated with endovesical therapy and 1 had distant metastases. Three patients were submitted to cystectomy, one for superficial recurrence and hematuria and two for invasive bladder recurrence. CONCLUSIONS: This study defines the MTDs of CDDP and 5-FU concomitantly administered with hyperfractionated radiotherapy. The low toxicity observed and the high CRs and bladder preservation rates deserve further study.

Linearized quantum-fluctuation theory of spectrally filtered optical solitons.

We study the quantum fluctuations of an optical nonlinear Schrödinger soliton after spectral filtering. The photon-number-bandwidth correlation of the emerging soliton produces squeezing in the photon number of the filtered soliton. Bandwidth oscillations caused by the interference of the soliton with the quantum-noise continuum, however, give oscillations of the photon-number squeezing and, in addition, prevent achievement of arbitrarily high values of squeezing through spectral filtering.

Flow cytometric and immunohistochemical correlations in high incidence human solid tumors.

475 patients with carcinoma at different sites (141 colon-rectum; 102 breast; 50 stomach; 48 kidney; 46 head and neck; 41 bladder; 47 other sites) submitted to surgery have been analyzed after histopathological staging and grading, by flow cytometry (monoparametric DNA content analysis) and immunohistochemistry (p53, c-erbB-2, and PCNA expression). In breast cancer patients the presence of receptors for estrogen (ER) and progesterone (PGR) has also been determined. Flow cytometry-derived parameters were DNA ploidy, fraction of cells in S-phase (SPF), and DNA content heterogeneity (multi-clonal stem cell lines with different DNA index and/or more than one subpopulations with different ploidy levels in different samples from the same tumor). Correlations of the results obtained by the different techniques have been attempted by the non-parametric Spearman's rank correlation approach. Significant associations (P < 0.05) were found between the histopathological, immunohistochemical and flow cytometric parameters considered in some anatomical regions, such as stomach (p53 vs DNA content aneuploidy and vs heterogeneity), colon-rectum (TNM vs p53 and vs heterogeneity), bladder (grading vs DNA content aneuploidy and vs heterogeneity). Tumor heterogeneity proved to be dependent on the number of tumor samples taken. The results of this preliminary assessment will subsequently be compared with the data obtained from a currently ongoing follow-up survey.

Timing jitter in soliton transmission with sliding filters.

We show that the coupling between amplitude and frequency f luctuations that is due to filter sliding significantly enhances timing jitter in soliton transmission controlled by in-line filters. This is the likely reason for the extra timing jitter observed in a recent soliton transmission experiment using sliding filters.

Transient four-wave mixing with a collinear pump and probe.

We propose a new heterodyne scheme for performing time-resolved four-wave mixing experiments with collinear pump and probe beams. The method is not limited by phase-matching requirements and permits the investigation of thick samples and waveguide devices such as semiconductor optical amplifiers.

Light depolarization owing to amplified spontaneous emission and Kerr nonlinearity in long-haul fiber links close to zero dispersion.

The interplay between amplif ied spontaneous emission noise and Kerr nonlinearity is shown to produce significant depolarization of light in long-haul transmission links operating close to zero dispersion. If polarization mode dispersion is neglected, a simple analytical theory predicts the length scale over which depolarization occurs. The analytical theory is compared with computer simulations, which also permit analysis of the case in which polarization mode dispersion is included.

Soliton transmission control with semiconductor amplifiers.

A signal propagating along a dispersive transmission line in which loss is compensated by semiconductor amplifiers suffers from strong memory effects induced by the amplifier saturation. Insertion of filters along a line of anomalous dispersion reduces the detrimental effects of the amplifier saturation.

Soliton transmission control by Butterworth filters.

Butterworth filters of second or higher order periodically inserted along a soliton transmission line, although they are flat at bandpass center, give to first order a nonzero restoring force for frequency and amplitude displacements. The amplified spontaneous emission generated at the filter center frequency is significantly less than that generated with fixed étalons for the same damping strength.