Evaluation of the fibromyalgia impact questionnaire at baseline as a predictor for time to pain improvement in two clinical trials of pregabalin.

BACKGROUND: The Fibromyalgia Impact Questionnaire (FIQ) is a patient-reported outcome that evaluates the impact of fibromyalgia (FM) on daily life. This study evaluated the relationships between the functional status of FM patients, measured with the FIQ at baseline, and median time to a clinically relevant pain reduction. METHODS: Data were derived from two randomised, placebo-controlled trials that evaluated pregabalin 300, 450 and 600 mg/day for the treatment of FM. The Kaplan-Meier (nonparametric) method was applied to estimate median times to 'transient' and 'stable' events. The transient event was defined as a ≥ 27.9% improvement on an 11-point daily pain diary scale (0 = no pain, 10 = worst possible pain), and the stable event was defined as the mean of the daily improvements ≥ 27.9% relative to baseline over the subsequent study duration starting on the day of the transient event. A parametric model using time-to-event analysis was developed for evaluating the relationship between baseline FIQ score and the median time to these events. RESULTS: Median time was longer among patients treated with placebo relative to pregabalin for the transient events (11-12 days vs. 5-7 days) and stable events (86 days vs. 13-29 days). A significant association was observed between baseline FIQ scores and median time to transient and stable events (p < 0.001). Median times to events were similar between the studies. For transient pain reduction events, median times ranged from 3.0 to 4.5 days for baseline FIQ scores of 10, and 9.1-9.6 days for FIQ scores of 100; for stable pain reduction events, the median time ranged from 11.0 to 13.0 days and from 27.0 to 28.5 days for baseline FIQ scores of 10 and 100 respectively. CONCLUSIONS: Time to a clinically relevant reduction in pain was significantly associated with FM severity at baseline as measured by the FIQ. Such an analysis can inform patient and physician expectations in clinical practice.

Characteristics of patients with fibromyalgia in France and Germany.

INTRODUCTION: Few studies have comprehensively assessed the burden associated with fibromyalgia (FM). This cross-sectional, observational study evaluates the impact of FM on patients in France and Germany. METHODS: A total of 299 FM patients were recruited from 33 physician offices in France and Germany during routine visits. Patients completed a survey that included the Brief Pain Inventory-Short Form (BPI-sf), Fibromyalgia Impact Questionnaire (FIQ), EuroQol 5D (EQ-5D) and the Hospital Anxiety and Depression Scale (HADS) to describe their pain, FM and health-related quality of life (HRQOL). FM severity was defined using patients' FIQ total scores with 0 to < 39, 39 to < 59 and 59-100, representing mild, moderate and severe FM, respectively. Site staff completed case report forms using patients' medical records. RESULTS: Mean (standard deviation, SD) age was 54.2 (12.6); 81% of patients were women. The mean (SD) FIQ total score was 53.3 (19.6); 33% and 44% of patients reported moderate and severe FM, respectively. Most patients (91%) were receiving prescription medications for FM during the study. Patients reported a mean (SD) EQ-5D health state valuation of 0.44 (0.33) and a mean (SD) BPI-sf Pain Severity Index score of 4.9 (1.8). Forty-one percent of patients reported some level of disruption in their employment because of FM; employed patients missed a mean (SD) of 2.2 (4.6) workdays during the past 4 weeks. An increase in FM severity was significantly associated with increased pain severity, productivity loss, sleep disturbance and higher anxiety and depression (p < 0.0001). CONCLUSIONS: There is a substantial burden of illness including treatment limitations for FM patients in France and Germany.

Resonant Raman and micro-Raman scattering from Si matrix with unburied beta-FeSi2 nanolayers.

Samples, representing Si matrix with nanolayers of the semiconducting beta-FeSi2 silicide are studied by Raman scattering. The unpolarized Raman spectra of the samples are measured in two different configurations. It is found that the characteristic beta-FeSi2 Raman modes are seen in the spectra, taken at incident angle of about 45 degrees , while only comparatively intensive broad feature is detected in a back-scattering geometry. The difference in the spectra is interpreted with the appearance of surface polariton modes of the optical phonons in the nanosized layers in near back-scattering geometry. The resonant Raman scattering is investigated at incident light angle of about 45 degrees and the energies of the interband transitions in the investigated energy range are determined. It is known that the resonant Raman scattering appears to be even more precise method for the determination of the interband transitions energies than the modulation spectroscopy. Thus we claim that the energies determined here are firstly determined with such a precision.

Raman scattering of Si matrix with randomly distributed nanoparticles of semiconducting silicides.

Samples, representing Si matrix with nanoformations of the semiconducting silicides beta-FeSi2 and Mg2Si are studied by Raman scattering. The unpolarized Raman spectra of the samples are interpreted in the framework of the appearance of interface-phonon polaritons. The theoretical dispersion relations of the interface-phonon polaritons in the system Si/silicide/Si are obtained from the Maxwell equations. The correspondence of the theoretical calculations and the experimental observations appeared to be sufficiently good. An evolution of the features in the Raman spectra on the experimental conditions is observed.

Effect of He-Ne laser treatment on the level of lipid peroxidation products in experimental cataract of rabbit eyes.

The effect of low-intensity laser irradiation on the processes of lipid peroxidation in lens homogenate and aqueous humor during experimental diquat-induced cataract of rabbit eyes was studied. The levels of primary and secondary products of lipid peroxidation (LPO), conjugated dienes and thiobarbituric acid reactive substances (TBARS), were evaluated. We found that the experimental cataract model leads to a significant increase in the content of conjugated dienes and in the content of TBARS both in lens homogenate and in aqueous humor. The data obtained support the important role of oxidative stress in the development of the diquat-induced cataract model. Low-intensity laser treatment does not provoke a significant decrease in conjugated dienes or in TBARS in either lens homogenate or aqueous humor. Although our therapeutic scheme led to a slightly decreased level of LPO products, we conclude that the effect of low-intensity laser-irradiation may depend on the dose applied, individual tissues and other factors.

The economics of upper gastrointestinal bleeding in a US managed-care setting: a retrospective, claims-based analysis.

OBJECTIVE: To assess 12-month healthcare resource utilization and costs associated with upper gastrointestinal (UGI) bleeding events. METHODS: Patients hospitalized with a UGI bleeding event were identified in US national health-plan claims data (1999-2003) and propensity matched to control patients without UGI bleeding in the same health plan. Matching criteria included age, gender, index date, Charlson Comorbidity Index score, geographic region, and prior medical utilization. RESULTS: A total of 9,033 UGI-bleed patients and 579,018 control patients met the inclusion criteria, yielding 4,651 matched pairs. After matching, differences between the UGI bleed and general population cohorts remained for office visits, ER visits, and ER costs during the 6-month baseline period prior to the index date. During the 12 months following the index date, both UGI-related healthcare utilization and total healthcare, medical, and pharmacy costs incurred by the UGI-bleed cohort were significantly greater (p< 0.0001) than those incurred by the general population cohort (mean of $20,405 vs. 3,652), even after excluding the initial hospitalization costs (mean of $11,228 vs. 3,652). Costs were primarily due to inpatient hospitalizations (mean of $13,059 for the UGI-bleed cohort vs. $729 for the general population cohort) and ambulatory services (mean of $4,037 for the UGI-bleed cohort vs. $1,537 for the general population cohort). Sixteen percent of the UGI-bleed cohort had a GI-related hospitalization, and about 40% of total costs occurred after the initial hospitalization. CONCLUSIONS: Patients with UGI bleeds experienced significantly higher (p< 0.0001) 12-month health-resource utilization and costs than patients without UGI bleeds. This study provides empirical evidence of the long-term economic burden associated with UGI bleeding. Interpretation of the results should take into account the lack of available information in claims data that could have an effect on study outcomes, such as particular clinical and disease-specific parameters that are not mitigated by propensity score and comorbidity index matching. In addition, this study is limited by the intensive demographic matching that was done between the two cohorts, which may have eliminated the sickest UGI patients and the healthiest general health-plan population patients.

[Neovascular age-related macular degeneration in Germany. Encroachment on the quality of life and the financial implications]. / Neovaskuläre altersabhängige Makuladegeneration in Deutschland. Beinträchtigung der Lebensqualität und ihre finanziellen Auswirkungen.

BACKGROUND: Approximately 35,000 cases of neovascular age-related macular degeneration (AMD) occur annually in Germany. The neovascular form of AMD (NV-AMD) is responsible for severe vision loss associated with the disease in 90% of the cases. This study was conducted to assess the humanistic and economic burden of NV-AMD in the German population. METHODS: A cross-sectional, observational study of subject self-reported functional health, well-being, and disease burden among elderly subjects with (n=83) and without (n=93) NV-AMD in Germany was conducted. Patients participated in telephone surveys involving the National Eye Institute Visual Function Questionnaire (NEI-VFQ-25), the EuroQol (EQ-5D), the Hospital Anxiety and Depression Scale (HADS), and also reported history of falls, fractures, and healthcare resource utilization. Furthermore, the healthcare utilization and unit costs for the NV-AMD patients were calculated. RESULTS: The mean age of NV-AMD patients was 77.2 years and 64% were female. NV-AMD patients reported significantly worse vision-related function and overall well-being than controls (adjusted mean scores: NEI-VFQ-25 overall scale: 51.3 vs 96.3; p<0.0001) and significantly more depression symptoms than controls (HADS depression: 6.2 vs. 2.7; p<0.0001). NV-AMD patients also reported that the need for assistance with daily activities was more than 10 times greater compared to controls (26.5% vs. 2.2%; p<0.0001) and the prevalence of falls was 3 times that of the control group (13.3% vs 4.3%; p=0.031). Annual NV-AMD costs per patient were 9871, 6 times that of elderly patients without NV-AMD ( 1559). Of the NV-AMD costs one-half were direct non-medical-related costs (assistance of ADL or social benefit) and one-third were direct medical costs. CONCLUSIONS: NV-AMD is associated with decreased functional abilities and quality of life, which result in an increase in healthcare resource utilization. Consequently, costs were higher for NV-AMD patients compared to controls. These findings emphasize the need for new NV-AMD treatments that will prevent vision loss and progression to blindness, and lessen the ensuing economic burden. Sponsored by Pfizer Inc. New York, US.

Delay in treating age-related macular degeneration in Spain is associated with progressive vision loss.

PURPOSE: To assess the impact on visual acuity of delays between diagnosis and treatment in patients with subfoveal neovascular age-related macular degeneration (NV-AMD) and to evaluate NV-AMD patients' emotional status before therapy initiation. METHODS: This retrospective, multicenter, epidemiological study included newly diagnosed NV-AMD patients registered in the Spanish national health system and referred to regional health centers for evaluation/treatment by a retinal specialist from 09/2005 to 03/2006. Records were reviewed and data abstracted at referring physicians' offices (diagnosis visit) and regional health centers (treatment visit). Treatment was at physicians' discretion. The Hospital Anxiety and Depression Scale was administered at the treatment visit (before therapy). RESULTS: Median time from the diagnosis to treatment visit was 2.3 months (95% confidence interval: 0.2-10.8 months). Vision loss had progressed at the treatment visit with a doubling in the percentage of patients with a visual acuity of 20/400 or worse (from 12.4 to 24.7%). The decrease in visual acuity from the diagnosis to the treatment visit was highly statistically significant (P<0.0001) as was the correlation between months to treatment and visual acuity change (r=0.5234, P<0.0001). Time from the diagnosis to the treatment visit remained a significant predictor of progressive vision loss when visual acuity at diagnosis and change in lesion size between diagnosis and treatment were controlled (P<0.0001). Patients with more severe vision loss prior to treatment tended to report more depression. CONCLUSIONS: Delayed treatment of patients newly diagnosed with NV-AMD is associated with substantial visual acuity loss.

[Humanistic burden and health resource utilization among neovascular age-related macular degeneration patients in France]. / Impact de la dégénérescence maculaire néovasculaire: données françaises.

OBJECTIVE: To assess the impact of bilateral neovascular age-related macula degeneration (NV-AMD) on function and health resource utilization (HRU) in France. PATIENTS AND METHODS: Cross-sectional study including 401 NV-AMD patients and 471 controls conducted in five countries in 2006. In both groups, demographic and clinical data were collected and the National Eye Institute Visual Function Questionnaire (NEI-VFQ-25), the EuroQoL (EQ-5D), the Hospital Anxiety and Depression Scale (HADS), and questionnaires on HRU were administered. RESULTS: Eighty-seven NV-AMD patients and 92 controls were recruited in France. The mean age of the NV-AMD patients was 79 (range, 65-95), and 64% were female. After adjusting for age, gender, and co-morbidities, compared to controls, NV-AMD patients reported substantially worse vision-related quality of life on the NEI-VFQ (adjusted mean, 44.4 [36.2-52.7] versus 91.8 [86.2-97.5], p<0.0001). HADS anxiety and depression scores were significantly worse in NV-AMD patients (anxiety score, 8.5 [6.3-10.8] versus 5.1 [3.5-6.7] p=0.0005; depression score: 7.1 [5.1-9.1] versus 2.9 [1.5-4.4] p<0.0001). Per patient yearly cost analysis showed significantly higher direct medical costs: 3396 euro versus 85 euro (p<0.0001), and indirect nonmedical-related costs (mainly for assistance with activities of daily living): 2985 euro versus 494 euro (p=0.014). CONCLUSIONS: NV-AMD patients in France reported substantially worse QoL and more anxiety and depression symptoms. The functional impact of blindness led to significantly higher health resource utilization in the AMD patients, resulting in higher total health costs compared to a similarly aged control group.

Quality of life in patients with age-related macular degeneration: results from the VISION study.

PURPOSE: To assess the impact of treatment with pegaptanib sodium vs usual care on vision-related quality of life (VRQoL) in patients with age-related macular degeneration (AMD). METHODS: VRQoL was a secondary end point in the trial, a prospective, randomized, double-masked, multicentre, dose-ranging study. Three doses of pegaptanib (0.3, 1, and 3 mg) were compared with usual care with respect to changes in VRQoL as indicated by the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ 25), administered at baseline and weeks 30 and 54. Four of the NEI-VFQ 25 domains were prospectively designated as primary: near vision, distance vision, role limitations, and dependency. Between-group differences were assessed using an analysis of covariance model with age, gender, and baseline score as covariates. RESULTS: NEI-VFQ 25 data were available for 569 subjects. At week 54, improvements in the distance vision and role limitations domains were greater in pegaptanib than usual care arms. No substantial increase in ocular pain was noted in pegaptanib-treated patients. No clear superiority of any particular dosage strength of pegaptanib was demonstrated, and no significant differences or trends favoured usual care on any domain score or the NEI-VFQ 25 composite score. The greatest VRQoL benefit was seen in responders (lost<3 lines) to treatment. CONCLUSION: The VISION trial provided evidence of trends in quality-of-life benefit associated with effective treatment of AMD using pegaptanib. Treatment with pegaptanib is expected to contribute significantly to VRQoL improvement for responder patients.

Pharmacodynamic of the antioxidant action of alpha-tocopherol and its derivatives in liver, brain, heart and skeletal muscles.

The aim of the present work was to determine the pharmacodynamics of antioxidant effect of alpha-tocopherol and its derivatives (alpha-tocopheryl esters and chromanols with different chain-length) in the animal tissues, as well as the role of cytochrome P-450 in biotransformation of these compounds. Alpha-tocopherol and its derivatives were injected intraperitoneally in rats or mice in a single dose of 100 mmol per kg b.w. The animals were sacrificed at different time intervals (0, 1, 2, 4, 8, 12, 24, 36 hours) and the liver, heart, brain and skeletal muscles were removed, homogenized and incubated with lipid peroxidation (LPO) inducers (Fe2+ + ascorbate). LPO was evidenced by the generated malone dialdehyde (MDA). Data were expressed as percentage of LPO inhibition by alpha-tocopherol or its derivatives as compared to control group. The kinetic curves of the inhibitory action of alpha-tocopherol and its derivatives on LPO were characterized by three phases: a phase of increasing antioxidant activity, a phase of maximal antioxidant activity (about 60-95% LPO inhibition), and a phase of decreasing antioxidant activity. Alpha-tocopheryl esters possessed dynamics of antioxidant action the same as alpha-tocopherol. Therefore the hydrolysis of alpha-tocopheryl esters in animal organism is not a limiting factor for their antioxidant effect. The alpha-tocopherol derivatives with short chain-length (C1, C6) had a shorter half-life in animal tissues as compared to alpha-tocopherol or its esters. In vitro experiments showed that C1 and C6 are substrates of cytochrome P-450. In contrast, alpha-tocopherol and its esters did not bind to cytochrome P-450 even at concentrations as high as 10 mmol/l. Apparently, C1 and C6 underwent biotransformation and were excreeted more quickly from the organism.