Real-life management of primary immune thrombocytopenia (ITP) in adult patients and adherence to practice guidelines.

Very few data exist on the management of adult patients diagnosed with primary immune thrombocytopenia (ITP). The objectives of this study were to describe the diagnostic and treatment patterns for ITP and to compare the findings to recent ITP guidelines. We retrospectively analyzed the medical records of adult ITP patients diagnosed with primary ITP between January 2011 and June 2012 and examined whether management strategies were consistent or not with eight recent guideline-recommended practices. Overall, median age at the diagnosis of the disease (n = 101) was 58 years and median platelet count 12 × 10(9)/L with 75.2 % of patients having symptoms of ITP. The study perceived two major shortcomings in the diagnostic approach: (1) failure to perform peripheral blood film examination in 22.8 % of patients, a test that is mandatory by all guidelines, and (2) ordinary bone marrow assessment in more than half of the patients at diagnosis (50.5 %), a test not routinely recommended by guidelines. Low appropriateness in therapeutic management of patients included (1) unjustified use of intravenous immunoglobulin in the absence of bleeding in 54.8 % of patients and (2) splenectomy not being deferred until 6-12 months from diagnosis (median 161 days). Data also reflect a trend towards the early use of thrombopoietin receptor agonists in the treatment of patients who are refractory to any first-line therapy. We have recognized important areas of inapropriateness in the diagnostic and therapeutic management of adult ITP patients. Compliance with established guidelines should be encouraged in order to improve patient outcomes.

Prophylaxis in severe forms of von Willebrand's disease: results from the von Willebrand Disease Prophylaxis Network (VWD PN).

The bleeding patterns of severe von Willebrand's disease (VWD) adversely affect quality of life, and may be life threatening. There is a presumed role for prophylaxis with VWF-containing concentrates, but data are scarce. The von Willebrand Disease Prophylaxis Network (VWD PN) was formed to investigate the role of prophylaxis in clinically severe VWD that is not responsive to other treatment(s).Using a retrospective design, the effect of prophylaxis was studied. Availability of records to document, or reliably assess, the type and frequency of bleeding episodes prior to, and after, the initiation of prophylaxis was required. Annualized bleeding rates were calculated for the period prior to prophylaxis, during prophylaxis and by primary bleeding indication defined as the site accounting for more than half of all bleeding symptoms. The Wilcoxon signed-rank test of differences in the medians was used. Sixty-one subjects from 20 centres in 10 countries were enrolled. Data for 59 were used in the analysis. The median age at onset of prophylaxis was 22.4 years. Type 3 VWD accounted for the largest number (N = 34, 57.6%). Differences in bleeding rates within individuals during compared with before prophylaxis were significant for the total group (P < 0.0001), and for those with primary bleeding indications of epistaxis (P = 0.0005), joint bleeding (P = 0.002) and GI bleeding (P = 0.001). The effect of prophylaxis was similar among those age < 18 years and those ≥ 18. One person developed an inhibitor during treatment. We conclude that prophylactic treatment of VWD is efficacious.

Effects of silicates from scaps of photovoltaic industries on powdery mildew of zucchini.

Silicon is the second most abundant element on earth's surface and its use can stimulate natural defense mechanisms in plants. The effect of silicate from scraps of photovoltaic industries against powdery mildew on zucchini (Cucurbita pepo) was evaluated under greenhouse conditions. Potted plants were inoculated with a spore suspension containing 1 x 10(5) cfu/ml. The following treatments have been carried out, 3 and 10 days after pathogen inoculation: chemical fungicide (propiconazole, TILT 25 EC, Syngenta); Bacillus subtilis (250 g/hl, Serenade, Intrachem); 1% and 0.1% sodium silicate (r = 1); 1% and 0.1% sodium silicate (r = 2); tap water as control. Disease incidence and severity were assessed 7, 14 and 21days after pathogen inoculation. Results showed that the application of 1% sodium silicate (r = 1) significantly reduced the powdery mildew to a level similar to chemical control. The other treatments, including Bacillus subtilis, reduced disease severity compared to water control, but were less efficient. The use of silicates from photovoltaic industries is a valid alternative for the control of powdery mildew on zucchini, in particular in organic farming. However, silicates might not be sufficient at higher disease incidence levels, and their use is more suitable within an integrated disease control strategy.

Prophylaxis in 10 patients with severe haemophilia A and inhibitor: different approaches for different clinical situations.

The effect of bypassing agents is not as predictable as replacement therapy with the deficient factor in inhibitor patients. Consequently, these patients have more levels of arthropathy than patients without inhibitors. Prophylaxis for inhibitor patients has gained attention over the last decade and some papers have reported that bypassing agents could work in the prevention of arthropathy. However, there is a lack data to support any specific agent or regimen or even to recommend their use in different clinical conditions. We report ten patients with haemophilia A and inhibitors treated prophylacticaly with bypassing agents (5 with FEIBA and 5 with NovoSeven). The variable conditioning the choice of one agent or the other was the intention to initiate of immune tolerance induction therapy (ITI) in the future. In 8/10 patients (4 in FEIBA group and 4 in rFVIIa group) there was a decrease of bleeding episodes while 9/10 maintained or increased their joint range of motion (ROM). In the rFVIIa prophylaxis group, prophylaxis can be considered primary since all of them had had less than one joint bleed before prophylaxis. Economic analysis showed that prophylaxis is an expensive treatment. In our experience both agents seem to be safe and effective in reducing the number of bleeds in patients with inhibitors. The anamnestic response provoked by FEIBA could be an issue while awaiting a decline in titres before ITI can be initiated and so rFVIIa may be the best option for prophylaxis in patients with inhibitors who have not yet begun ITI.

Donor infection and transmission to the recipient of a solid allograft.

Transmission of infection from donor to recipient is a potential complication of transplantation. More data on this issue are needed to expand the insufficient donor pool. This study evaluates the incidence of donor nonviral infection, transmission from infected donors and the effect of donor infection on 30-day recipient survival. Data from 211 infected donors contributing to 292 (8.8%) of 3322 consecutive transplant procedures within RESITRA (Spanish Research Network for the Study of Infection in Transplantation) were prospectively compiled and analyzed. Lung was the most likely transplanted organ carried out with an infected donor and Staphylococcus aureus was the most commonly isolated microorganism. In more than a half of donors, the lung was the site of infection. Donor-to-host transmission was documented in 5 patients out of 292 (1.71%), 2 of whom died of the acquired infection (40%). Nonetheless, there was no difference in 30-day patient survival when comparing transplant procedures performed with organs from infected or uninfected donors. In conclusion, donor infection is not an infrequent event, but transmission to the recipient is quite low. Hence, with careful microbiological surveillance and treatment, the number of organs available for transplantation may be increased.

Experiences in the prevention of arthropathy in haemophila patients with inhibitors.

Haemophilia patients with inhibitor have a higher level of arthropathy and more severe joint morbidity than patients without inhibitors. In recent years, interest has grown in the possibility that bypassing agent regimens could prevent bleeding and, consequently, arthropathy in inhibitor patients. Nevertheless, doubts about efficacy, complications and cost exist, questioning the justification of an uncertain prophylaxis in patients with inhibitors. Activated prothrombin complex concentrate (aPCC) has been used in more than 70 haemophilia patients with inhibitors in different clinical situations. aPCC prophylaxis seems to be safe and effective for the reduction of bleeding episodes in some patients. Recombinant activated factor VII (rFVIIa) has been employed prophylactically in over 44 haemophilia patients with inhibitors; 22 patients were included in the only randomized, prospective clinical trial of bypassing agents in prophylaxis. Bleeding frequency was reduced and this reduction was maintained during the postprophylaxis period. No thromboembolic events were reported during prophylaxis with rFVIIa. Although the effect of aPCC can last longer than that of rFVIIa, their efficacy rates are similar, suggesting that the biological effect of rFVIIa is actually much longer than indicated by its short plasma half-life. aPCC contains residual factor VIII antigen and may cause an anamnestic response in the inhibitor titre. This is crucial when immune tolerance induction is postponed to allow the inhibitor titre to decline to <10 Bethesda Units. In this setting, aPCC is not recommended as a first-line prophylaxis because of its potential to protract anamnesis, and rFVIIa is the preferred agent.

Clinical efficacy in bleeding and surgery in von Willebrand patients treated with Fanhdi a highly purified, doubly inactivated FVIII/VWF concentrate.

Therapy with factor VIII/von Willebrand factor (FVIII/VWF) concentrate is the mainstay therapy in patients with von Willebrand disease (VWD) unresponsive to desmopressin. There are several commercially available FVIII/VWF concentrates that have been tested in VWD patients. We retrospectively analized the clinical efficacy in bleeding episodes and surgery of a highly purified FVIII/VWF complex with two inactivation steps (Fanhdi) in VWD patients. Sixty patients were included in the study. Treatment schedule consisted of one or more doses (standard dose 40 IU/kg body weight of FVIII) of Fanhdi. One hundred and fifty bleeding episodes were treated. These were: 28 serious bleedings; 92 moderate and 30 mild. An excellent clinical efficacy in almost 95% of cases was observed. Fanhdi was administered during 66 surgical procedures (38 major and 28 minor) with an overall efficacy of 98%. Fanhdi a highly purified, doubly virus-inactivated FVIII/VWF concentrate, with a high content of active VWF and an excellent record of clinical safety, is a valid choice in treating VWD.

Simultaneous estimation of human and exoskeleton motion: A simplified protocol.

Adequate benchmarking procedures in the area of wearable robots is gaining importance in order to compare different devices on a quantitative basis, improve them and support the standardization and regulation procedures. Performance assessment usually focuses on the execution of locomotion tasks, and is mostly based on kinematic-related measures. Typical drawbacks of marker-based motion capture systems, gold standard for measure of human limb motion, become challenging when measuring limb kinematics, due to the concomitant presence of the robot. This work answers the question of how to reliably assess the subject's body motion by placing markers over the exoskeleton. Focusing on the ankle joint, the proposed methodology showed that it is possible to reconstruct the trajectory of the subject's joint by placing markers on the exoskeleton, although foot flexibility during walking can impact the reconstruction accuracy. More experiments are needed to confirm this hypothesis, and more subjects and walking conditions are needed to better characterize the errors of the proposed methodology, although our results are promising, indicating small errors.

Data on genotypic distribution and linkage disequilibrium of several ANRIL polymorphisms in hemodialysis patients.

A long non-coding RNA called ANRIL located on chromosome 9p21.3 has been identified as a novel genetic factor associated with cardiovascular disease. Investigation of several single nucleotide polymorphisms (SNPs) of Noncoding Antisense RNA in the INK4 Locus (ANRIL) gene are of particular interest. This article reports data related to the research article entitled: "Association of ANRIL gene polymorphisms with major adverse cardiovascular events in hemodialysis patients" (Arbiol-Roca et al. [1]). Data presented show the genotypic distribution of four selected ANRIL SNPs: rs10757278, rs4977574, rs10757274 and rs6475606 in a cohort constituted by 284 hemodialysis patients. This article analyzes the Hardy-Weinberg disequilibrium of each studied SNP, and the linkage disequilibrium between them.

Association of ANRIL gene polymorphisms with major adverse cardiovascular events in hemodialysis patients.

BACKGROUND: Cardiovascular disease is the leading cause of death in patients with chronic kidney disease (CKD). Single nucleotide polymorphisms (SNPs) in ANRIL gene have been associated with higher cardiovascular morbidity and mortality in general population. The main objective was to ascertain whether ANRIL polymorphisms could identify risk of major adverse cardiovascular event (MACE) in patients starting on hemodialysis (HD). METHODS: This was a prospective observational cohort study. 284 CKD patients starting on HD were included in the study and followed until achievement of the primary end-point (MACE) or end of the study. All patients were genotyped for four ANRIL SNPs (rs10757278, rs4977574, rs10757274 and rs6475606). Kaplan-Meier curves and multivariate Cox survival analyses, together with multiple logistic regression were used to analyze the association between ANRIL SNPs and MACE. RESULTS: We found that ANRIL SNP rs10757278 was a representative SNP of a strong linkage disequilibrium block and showed significant genotypic associations with MACE in hemodialysis patients. Homozygous patients for the risk allele (GG) showed 2.17 (1.05-4.49) fold increased risk of MACE during hemodialysis than carriers of the protective allele (AA or AG). Diabetes mellitus was a strong enhancer of this effect. CONCLUSIONS: Our results indicate that ANRIL polymorphisms may confer risk to development of MACE in incident patients on hemodialysis.

Toxic keratolysis from combined use of nonsteroid anti-inflammatory drugs and topical steroids following vitreoretinal surgery.

PURPOSE: To evaluate the corneal complications associated with the combined use of non-steroid anti-inflammatory drugs (NSAIDs) and topical steroids following vitreoretinal surgery. METHOD: Description of corneal lesions in three patients after vitrectomy with use of topical ketorolac and prednisolone acetate. RESULTS: Three eyes of three patients developed an atrophic central corneal ulcer with stromal thinning following a pars plana vitrectomy under local anesthesia. Lesions were asymptomatic and were found during a routine examination 2, 3, and 8 weeks after surgery, respectively. Surgical indications were as follows: a preretinal membrane, choroidal neovascularization, and massive uveal effusion following cataract surgery. Topical postoperative treatment was as follows: ketorolac 4 times a day, a combination of prednisolone acetate, polymyxin B, and neomycin 6 times a day, and 1% cyclopentolate 3 times a day. Suspension of ketorolac and ocular occlusion led to the resolution of corneal lesions between 2.5 and 3 months later, yielding a central superficial scarring, which showed no changes after a follow-up of 3 years. CONCLUSIONS: Toxic keratolysis may appear as a secondary effect of the combined use of topical NSAIDs and steroids following vitreo retinal surgery and must be taken into account in the differential diagnosis of postoperative corneal lesions.

Drug Cost Avoidance in Prostate Cancer Clinical Trials.

OBJECTIVES: Economic impact of prostate cancer is increasing in relation to its increased incidence and increased patient survival. Clinical trials are essential to evaluate the efficacy and safety of new treatments but may also result in economic benefits by avoiding the cost of the drug. Our objective is to determine the avoided cost in investigational drugs in clinical trials of prostate cancer conducted in a period of 18 years in a tertiary center. MATERIAL AND METHODS: We carried out an observational of prevalence study with retrospective collected data of clinical trials involving currently marketed drugs and cost avoidance during the study period (1996-2013) was calculated. RESULTS: We include in this review five clinical trials on prostate cancer that met selection criteria of 18 performed. All of them were phase III, multicenter, international and with current marketed drugs. 136 patients were included. Total cost avoidance of 696,002€ and an average cost avoidance by clinical trial of 139,200€ were obtained. Average cost avoidance per patient was 5,118€. CONCLUSION: Cost avoidance in investigational drugs is a tangible benefit of clinical trials, whose realization is a source of economic benefits for the hospital, not only by directly generated by each trial. Clinical trials are an exceptional framework for progress in clinical research and real savings for the health system.

Comparative study of vitrectomy with and without vein decompression for branch retinal vein occlusion: a pilot study.

PURPOSE: To report the clinical outcomes in patients undergoing pars plana vitrectomy with and without vein decompression for treatment of branch retinal vein occlusion (BRVO). METHODS: Thirty-five eyes with macular edema and visual acuity worse than 20/100 secondary to BRVO were prospectively evaluated. Vitrectomy with posterior hyaloid removal and vein decompression at the arteriovenous crossing was performed on 15 eyes (Group 1); consecutively, the same technique without vein decompression was performed on 20 eyes (Group 2). Primary outcome was visual acuity and secondary outcomes were resolution of macular edema and development of neovascularization. RESULTS: No differences were found between groups in either patient age (p = 0.566) or preoperative visual acuity (p = 0.505). No differences were found in visual acuity at 3 (p = 0.651), 6 (p = 0.697), 9 (p = 0.763), 12 (p = 0.881), or 18 (p = 0.748) months. Mean time for macular edema resolution and visual acuity improvement was 9 months in both groups, with a mean improvement of 3.5 +/- 2.35 lines in Group 1 and 3.2 +/- 2.97 lines in Group 2. No eyes in either group developed new vessels. CONCLUSIONS: Results suggest that vitrectomy with posterior hyaloid removal without vein decompression can resolve macular edema, improve vision, and prevent development of new vessels in BRVO.

Multifocal choroiditis after allogenic bone marrow transplantation.

PURPOSE: To describe the clinical manifestations of multifocal choroiditis presumed to be secondary to allogenic bone marrow transplantation after development of self-tolerance to chronic graft-versus-host disease (GVHD). METHODS: Case report. A 17-year-old male who received an allogenic bone marrow transplant (BMT) from his HLA-identical sister. RESULTS: One year after BMT, grade II chronic GVHD developed. Two years later, vision deteriorated to 20/50 R.E. and 20/400 L.E. Ophthalmoscopic examination showed multiple chorioretinal punched-out scars throughout the posterior pole and mid-periphery of both eyes. Fluorescein angiography showed four choroidal neovascular membranes (CNVMs) in the right eye that were surgically removed, and a subfoveal disciform scar in the left eye. CONCLUSIONS: Multifocal choroiditis is a possible complication related to allogenic BMT. It should be included as a late cause of BMT-associated choroidopathy. Surgical removal of vision-threatening CNVMs is a reasonable approach.

[Hemodialysis and complement (author's transl)]. / Hemodiálisis y complemento.

After observing alterations in the activity of the serum complement in patients undergoing periodic hemodialysis, the authors performed a preliminary study to determine repeatedly the activity of C3, C4, and CH50 in 44 patients. They discovered a consistent drop in C3 and CH50 while C4 remained normal. An attempt to explain these findings with information from the literature offered no more than a hypothesis for further study. While the possibility of a decline in the synthesis of the complement factors cannot be disregarded, the authors believe it is much more probable that they are consumed at a rate higher than normal. Since the C4 factor does not appear to be involved, activation is probably along the alternative pathway. Defective synthesis cannot be attributed to liver disease because the latter is not always present and because there is no relationship between C3 levels and levels of albumin or the presence of hepatopathy. The literature was reviewed for data that might support the idea that the complements in these patients are activated continuously by some process in connection with dialysis, by chemical products employed for to clean the machines, by commonly administered drugs, etc. Because so few data could be found on the subject, the authors consider that is necessary to study these mechanisms and their repercussions over a longer period of time.

[Diabetic papillopathy and type 2 diabetes]. / Papilopatía diabética y diabetes tipo II.

CASE REPORT: We report a case of a 62-year-old man with type II diabetes mellitus and mild impairment of visual acuity with bilateral optic disc edema. Visual field examination showed enlargement of right blind spot and an inferior arcuate defect in the left eye. Blood pressure, neuroimaging evaluation and cerebrospinal fluid analysis were normal. Spontaneous resolution was observed six weeks later. DISCUSSION: Although the diabetic papillopathy was initially described in juvenile diabetics, recently an afflicted older subpopulation with type II diabetes has been reported to develop this condition. We discuss the clinical characteristics, pathogenesis and differential diagnosis of this clinical entity.

[Quality indicators in the storage and dispensing process in a Hospital Pharmacy]. / Indicadores de calidad en el proceso de almacenamiento y dispensación de medicamentos en un Servicio de Farmacia Hospitalaria.

OBJECTIVE: To establish indicators for the evaluation of the quality of the storage and dispensing processes related to semiautomatic vertical (SAVCS) and horizontal (SAHCS) carousel systems. MATERIAL AND METHODS: Descriptive observational study conducted between January-December 2012. Definition of quality indicators, a target value is established and an obtained value is calculated for 2012. RESULTS: Five quality indicators in the process of storage and dispensing of drugs were defined and calculated: indicator 1, error filling unidose trolleys: target (<1.67%), obtained (1.03%); indicator 2, filling accuracy unidose trolleys by using an SAVCS: target (<15%), obtained (11.5%); indicator 3, reliability of drug inventory in the process of drug entries using an SAHCS: target (<15%), obtained (6.53%); indicator 4, reliability of drug inventory in the picking process of orders replacement stock of clinical units using an SAHCS: target (<10%), obtained (1.97%); indicator 5, accuracy of the picking process of drug orders using an SAHCS: target (<10%), obtained (10.41%). CONCLUSIONS: Establishing indicators has allowed the quality in terms of safety, precision and reliability of semiautomatic systems for storage and dispensing drugs to be assessed.