Long-term efficacy of omalizumab in seven patients with treatment-resistant chronic spontaneous urticaria.

BACKGROUND: Monoclonal anti-IgE antibody omalizumab is a promising therapeutic option in patients with chronic urticaria (CU) resistant to non-sedating H1-antihistamines (nsAH). However, data about its long-term efficacy and safety are still scant. OBJECTIVE: We retrospectively analysed the clinical course of patients with severe recalcitrant CU that were treated in our department with omalizumab for a period greater than 24 months. METHODS AND PATIENTS: Seven patients (six females, median 43 years) treated for a median of 35 months have been evaluated. Before treatment, all suffered from persistent symptoms despite receiving high doses of nsAH [4×/day], leukotriene antagonists and prednisolone (10-30 mg/day for a median duration of 48 months). Response to treatment was assessed using urticaria activity score (UAS) and a combined symptom/medication score. RESULTS: There was a complete remission of disease in four patients after the first dose of omalizumab. Before the 5th administration, all patients had a UAS of 0. We found a significant improvement in UAS between pre-treatment and first dose (p=0.017) and a gradual decrease in the symptom/medication score over the course of the first five administrations. Tapering of prednisolone was possible in all patients. Administration intervals were gradually increased, although all experienced resurgence of symptoms in cycles greater than six weeks. There were no reported adverse reactions attributable to the drug. CONCLUSION: Omalizumab was a safe and effective corticosteroid alternative for maintaining long-term remission of symptoms in these patients. Treatment intervals required individual patient-by-patient determination. The drug did not seem to alter the natural history of the disease.

Acute effects of resistance training with local vibration.

The aim of this study was to verify the acute effects of the application of local vibration on upper limbs during resistance training on the number of maximum repetitions, metabolic and hormonal responses. 32 volunteers performed a maximum voluntary contraction test during a lat pulldown exercise. After the test, all volunteers underwent one conventional resistance training session and one resistance training session with local vibration. In both interventions, volunteers performed 4 sets with the highest possible number of repetitions of the lat pulldown exercise at 55% of maximum voluntary contraction. During the vibratory resistance training intervention, vibration was locally applied (20-Hz and 12-mm). During the conventional resistance training, volunteers performed the same procedures without vibration. Blood samples were taken at each experimental session before and 5 min after the end of each intervention. No significant differences were observed in number of maximum repetitions between the series of vibratory and conventional training. Serum testosterone, cortisol and lactate were significantly increased after 2 interventions. Vibratory resistance training induced greater increases in testosterone and lactate concentrations. No significant changes were found in creatine kinase, creatinine or urea concentration. These data indicate that local vibration increases the metabolic and anabolic response to the resistance training, without changing the training volume.

Monocyte activation is a feature of common variable immunodeficiency irrespective of plasma lipopolysaccharide levels.

Common variable immunodeficiency disorders (CVID), the most frequent cause of symptomatic primary immunodeficiency, are defined by impaired antibody production. Notwithstanding, T cell activation and granulomatous manifestations represent the main causes of CVID morbidity even in patients receiving immunoglobulin (Ig) G replacement therapy. Additionally, gut pathology is a frequent feature of CVID. In this study, we investigated monocyte imbalances and their possible relationship with increased microbial translocation in CVID patients. Monocyte subsets were defined according to CD14 and CD16 expression levels and evaluated in terms of human leucocyte antigen D-related (HLA-DR), CD86 and programmed death-1 molecule ligand 1 (PD-L1) expression by flow cytometry, in parallel with the quantification of plasma lipopolysaccharide (LPS) and serum levels of soluble CD14 (sCD14), LPS-binding protein (LBP) and anti-LPS antibodies. CVID patients (n=31) featured significantly increased levels of serum sCD14 and an expansion of CD14(bright) CD16(+) monocytes in direct correlation with T cell and B cell activation, the latter illustrated by the frequency of the CD21(low) CD38(low) subset. Such alterations were not observed in patients lacking B cells due to congenital agammaglobulinaemia (n=4). Moreover, we found no significant increase in circulating LPS or LBP levels in CVID patients, together with a relative preservation of serum anti-LPS antibodies, in agreement with their presence in commercial IgG preparations. In conclusion, CVID was associated with monocyte imbalances that correlated directly with T cell activation markers and with B cell imbalances, without an association with plasma LPS levels. The heightened monocyte activated state observed in CVID may represent an important target for complementary therapeutic strategies.

Chronic effects of different frequencies of local vibrations.

The aim of this study was to compare the chronic effects of different frequencies of mechanical vibrations, applied in the direction of the resultant muscle forces' vector addition, on the performance of the lower extremities. After performing the maximal voluntary contraction (MVC), squat jump (SJ), countermovement jump (CMJ), multiple vertical jumps and running speed tests, 55 male volunteers were distributed into 4 groups: an Isometric group, an 8-Hz group, a 26-Hz group and a Control group. After a 4-week training period, the same tests were performed. The training groups reached a significant increase of the MVC, but the increases of the 8-Hz (23.2%) and 26-Hz (22.2%) groups were higher than the Isometric group (12.1%). A significant increase was observed between SJ and CMJ values measured at the pre-test and the post-test stages in the 8-Hz (SJ=11.1%; CMJ=8.7%) and 26-Hz groups (SJ=9.6%; CMJ=7.5%). No differences were observed between 8-Hz and 26-Hz groups. The application of vibrations of 8 Hz and 26 Hz, directed to the resulting muscle forces, was able to increase the performance of the lower extremities. This kind of local vibration did not produce positive effects on multiple vertical jumps or running speed.

Cost-effectiveness of omalizumab in real world uncontrolled allergic asthma patients.

OBJECTIVE: To estimate the cost-effectiveness of omalizumab compared with standard of care in the treatment and control of severe persistent asthma, using the outcomes from the Portuguese subpopulation of the eXpeRience registry. METHODS: This was a pragmatic cost-effectiveness analysis based on real world data from the eXpeRience registry which recruited 62 patients with uncontrolled persistent allergic asthma from 20 participating centers in Portugal. Response to omalizumab treatment was measured prospectively up to 24 months by the physician's Global Evaluation of Treatment Effectiveness (GETE). Retrospective data on patients' clinical symptoms, asthma control, lung function, exacerbations, and healthcare utilization were available for up to 12 months before omalizumab initiation and served as the standard of care comparator. The number of exacerbations (severe and non-severe), the number of clinical episodes, the number of days absent from work and/or school, and GETE response to therapy were considered as effectiveness outcomes. Following a societal perspective, as cost indicators, both direct and indirect costs were considered. Direct costs relate to the cost of omalizumab, standard of care and clinical episodes (emergency room visits, hospitalizations, and unscheduled doctor visits). Indirect costs relate to the societal cost of work absenteeism. Unit costs for clinical episodes and drugs were taken from official sources within the Portuguese Health Authority. A univariate sensitivity analysis was performed. RESULTS: A rate of 1.5 exacerbations per patient-year was estimated following omalizumab treatment compared with 8.2 exacerbations per patient-year prior to omalizumab initiation, implying an 82.1% reduction in the incidence of exacerbations following omalizumab treatment relative to standard of care alone. A 54.1% reduction in GETE score was also observed in favor of omalizumab treatment. The mean cost per person-year was 3023є in the 12 months of standard of care prior to omalizumab and 16,111є in the period of treatment with omalizumab. The incremental cost-effectiveness ratios were 2244є/exacerbation avoided, and 1750є/unit decrease in GETE classification. CONCLUSION: Our results demonstrate that adding omalizumab to the treatment of patients with uncontrolled severe persistent asthma reduces the number of exacerbations, improving overall treatment effectiveness at an acceptable cost from a societal perspective.

Enxertos vasculares homólogos e heterólogos conservados em glicerina na fleboplastia da jugular em eqüinos / Arterial homograft and venous heterograft conserved in glycerin in the phleboplasty of the jugular in equines

Doze eqüinos foram divididos aleatoriamente em dois grupos de seis animais (grupos I e II), com a finalidade de estudar a compatibilidade tecidual e a propriedade de indução de trombos de dois tecidos biológicos conservados em glicerina a 98 por cento. Esses tecidos foram usados na restauração da jugular externa e se constituíram de artéria carótida comum homóloga (ACCHo), no grupo I, e veia jugular externa heteróloga (VJEHe), no grupo II. Para a restauração, utilizaram-se duas técnicas de anastomose da jugular, sendo, no grupo I, a técnica de bypass e, no grupo II, a substituição de um segmento da jugular esquerda por meio de anastomose vascular término-terminal. Para avaliar a trombogênese local e a histocompatibilidade, foram realizados exames clínicos, hematológicos, ecoDopplercardiográficos e histológicos dos segmentos vasculares enxertados. Os segmentos foram colhidos após 45 dias da avaliação pós-operatória, tendo a jugular direita como testemunha para os exames histológicos. Ambos os tecidos foram compatíveis quando implantados nos eqüinos, sem processo inflamatório acentuado, indicativo de rejeição. A técnica de bypass não foi eficiente na restauração da jugular, ocorrendo trombose obliterante dos enxertos de ACCHo. A substituição completa do segmento da jugular por VJEHe pode ser viável para o restabelecimento do fluxo sangüíneo da jugular de eqüinos, desde que se mantenha a igualdade dos diâmetros entre o enxerto e o vaso receptor.