Tacrolimus vs. Azathioprine in myasthenia gravis treatment: a multicenter, prospective, randomized, double blind, head to head clinical trial

Current evidences show that tacrolimus could be a good therapeutic option in patients non-responsive to first-line treatments and even it could become one of the first-line drugs for treating MG. Our study will try to determine the effectivity and safety of tacrolimus in 190 myasthenia gravis patients with suboptimal response to azathioprine: after 12 months of treatment they will be randomized to continue with azathioprine or they will be switched to tacrolimus. Patients will follow the allocated treatment during 14 months and the response will be assessed as well as adverse effectsPURPOSE: To compare azathioprine vs. tacrolimus effectivity and safety in MG patients with suboptimal response to azathioprine at 12 monthsDESIGN: A 14 months multicenter, prospective, randomized, double blind, head to head clinical trial

Targeted vs. standard treatment against Helicobacter pylori: safety assessment clinical trial

Helicobacter pylori (H. pylori) is a gram negative bacteria that represents a considerable global burden in the world and is related to many gastrointestinal diseases (peptic ulcer, gastric MALT lymphoma or gastric cancer). Currently the triple standard therapy is less used as there is an increase of the clarithromycin resistance. Therefore patients have to receive several lines of treatment with the consequence of adverse events and the possibility to interrupt the treatment. This is why the main objective is to determine if making a culture and antibiogram to do a targeted treatment cause less adverse events with the same eradication than making an empirical treatment to eradicate H. pylori. The secondary objective is to determine the prevalence of resistance to clarithromycin in the province of GironaThis is a multicentre clinical trial without blinding; patients are selected by non-probabilistic sampling, with a total sample of 868 patients randomized in two equal groups of 434 patients in each group. The study will last 2 years. The endpoints will be to evaluate the adverse events and eradication of each group of patients. Also it will be evaluated the resistance to clarithromycin

Percutaneous access versus standard femoral exposure for endovascular abdominal aortic aneurysm repair: a randomized, controlled trial

The treatment of abdominal aortic aneurysm (AAA) has shifted from the exposure of the aorta artery in an open repair technique to a small groin cut in an endovascular repair. Recently, a percutaneous access for endovascular repair has appeared. This new technique aims to minimize the complications of the common femoral artery exposure, the patient discomfort and the length of hospitalizationObjectives: To compare the proportion of discharged patients within the first 48 postoperative hours of two common femoral artery accesses for endovascular repair of AAA: the open exposure technique and the percutaneous technique. Secondary objectives include to evaluate the total procedure time, the femoral access complications, the need for extra analgesia and the patient satisfaction and groin discomfort of the two techniquesDesign: Randomized controlled trial conducted between 2014 and 2017Participants: Patients diagnosed with abdominal aortic aneurysm with elective endovascular repair indication

Packet backbone design differences between commercial network and Container Trial System of LTE/SAE

The mobile networks of earlier and current generations, or 2G and 3G networks, provide users voice and packet services with higher transmission rates and good quality over the same core network. When developing the next generation of mobile networks the current quality of services needs to be maintained. This thesis concentrates on the next generation mobile network, especially on the evolution of the packet network part. The new mobile network has requirements for the common packet backbone network, Mobile Packet Backbone Network, which is additionally discussed in this study. The next generation mobile network, called LTE/SAE, is currently under testing. The test system is called Container Trial System. It is a mini sized LTE/SAE site. The LTE/SAE is studied in this thesis concentrating on the evolved packet core, the SAE part of the composition. The empirical part of the study compares the LTE/SAE Container Trial System and commercial network designs and additionally produces documentation for internal personnel and customers. The research is performed by comparing the documentations and specifications of both the Container Trial System and commercial network. Since the LTE commercial network is not yet constructed, the comparison is done theoretically. The purpose is furthermore to find out if there are any design issues that could be done differently in the next version of the Container Trial System.

Patson Approach versus the Standard Approach for increasing breast reconstruction rates in women undergoing mastectomy. A randomized, controlled, open-label clinical trial

Breast cancer is the most prevalent neoplasm among women in the majority of countries worldwide. Breast cancer treatment include mastectomy which is associated to strong impact in women. Breast reconstruction is an option for many women to re-establish their body image and also to decrease psychological impact. However, breast reconstruction rates are low and many factors are involved in not undergoing breast reconstruction. Patient involvement in the decision-making process increases breast reconstruction rates and is associated to higher satisfaction and less anxiety and depression symptoms. More physician-patient relation and more education in terms of breast reconstruction are needed to achieve our objective. A new approach of medical care, called Patson Approach, is created in order to meet our goal with more patient involvement, as well as, physician and psychological counsellingObjective: to increase breast reconstruction rates in women who are candidates for breast reconstruction after mastectomy and are included in the Patson Approach compared to women included in the Standard ApproachMethods: the study design will be a randomized, controlled, open-label clinical trial. 62 patients will be recruited during two years and randomly divided in two groups, 31 will be included in the Standard Approach and 31 will be included in the Patson Approach. Preoperative and postoperative appointments are established in order to do a follow-up of the patients and collect all the data

Qualitative Characteristics and Quantitative Measures of Solution's Reliability in Discrete Optimization: Traditional Analytical Approaches, Innovative Computational Methods and Applicability

The purpose of this thesis is twofold. The first and major part is devoted to sensitivity analysis of various discrete optimization problems while the second part addresses methods applied for calculating measures of solution stability and solving multicriteria discrete optimization problems. Despite numerous approaches to stability analysis of discrete optimization problems two major directions can be single out: quantitative and qualitative. Qualitative sensitivity analysis is conducted for multicriteria discrete optimization problems with minisum, minimax and minimin partial criteria. The main results obtained here are necessary and sufficient conditions for different stability types of optimal solutions (or a set of optimal solutions) of the considered problems. Within the framework of quantitative direction various measures of solution stability are investigated. A formula for a quantitative characteristic called stability radius is obtained for the generalized equilibrium situation invariant to changes of game parameters in the case of the H¨older metric. Quality of the problem solution can also be described in terms of robustness analysis. In this work the concepts of accuracy and robustness tolerances are presented for a strategic game with a finite number of players where initial coefficients (costs) of linear payoff functions are subject to perturbations. Investigation of stability radius also aims to devise methods for its calculation. A new metaheuristic approach is derived for calculation of stability radius of an optimal solution to the shortest path problem. The main advantage of the developed method is that it can be potentially applicable for calculating stability radii of NP-hard problems. The last chapter of the thesis focuses on deriving innovative methods based on interactive optimization approach for solving multicriteria combinatorial optimization problems. The key idea of the proposed approach is to utilize a parameterized achievement scalarizing function for solution calculation and to direct interactive procedure by changing weighting coefficients of this function. In order to illustrate the introduced ideas a decision making process is simulated for three objective median location problem. The concepts, models, and ideas collected and analyzed in this thesis create a good and relevant grounds for developing more complicated and integrated models of postoptimal analysis and solving the most computationally challenging problems related to it.

Induction of labor with titrated oral misoprostol solution versus oxytocin in term pregnancy: randomized controlled trial

PURPOSE: To evaluate the effectiveness and the safety of orally administered misoprostol in comparison to intravenously infused oxytocin for labor induction in term pregnant women. METHODS: Between 2008 and 2010, a total of 285 term pregnant women whom were candidate for vaginal delivery were assessed for eligibility to enter the study. Twenty five patients were excluded for different reasons; and 260 included women were randomly assigned to one of the two groups according to the method of treatment, misoprostol or oxytocin. The misoprostol group received 25 µg every 2 hours for up to 24 hours for induction. The oxytocin group received an infusion of 10 IU which was gradually increased. The time from induction to delivery and induction to the beginning of the active phase and successful inductions within 12, 18, and 24 hours were recorded. The trial is registered at irct.ir, number IRCT2012061910068N1. RESULTS: Failure of induction, leading to caesarean section was around 38.3% in the oxytocin group and significantly higher than that of the misoprostol group (20.3%) (p<0.001). Despite the more prevalent failure in the oxytocin group, the mean time intervals from induction to active phase and labor of this group were both significantly less than the misoprostol group (10.1±6.1 and 13.2±7.7 versus 12.9±5.4 and 15.6±5.1 hours respectively, both p-values were <0.05). Maternal and fetal complications were comparable between groups except gastrointestinal symptoms which were encountered more frequently in the misoprostol (10.9 versus 3.9%, p=0.03). CONCLUSIONS: Misoprostol is a safe and effective drug with low complications for the induction of labor. Failure is seen less with misoprostol and caesarean sections are less frequently indicated as compared to oxytocin.

The effect of soy dietary supplement and low dose of hormone therapy on main cardiovascular health biomarkers: a randomized controlled trial

PURPOSE: To assess the effects of a soy dietary supplement on the main biomarkers of cardiovascular health in postmenopausal women compared with the effects of low-dose hormone therapy (HT) and placebo.METHODS: Double-blind, randomized and controlled intention-to-treat trial. Sixty healthy postmenopausal women, aged 40-60 years, 4.1 years mean time since menopause were recruited and randomly assigned to 3 groups: a soy dietary supplement group (isoflavone 90mg), a low-dose HT group (estradiol 1 mg plus noretisterone 0.5 mg) and a placebo group. Lipid profile, glucose level, body mass index, blood pressure and abdominal/hip ratio were evaluated in all the participants at baseline and after 16 weeks. Statistical analyses were performed using the χ2 test, Fisher's exact test, Kruskal-Wallis non-parametric test, analysis of variance (ANOVA), paired Student's t-test and Wilcoxon test.RESULTS: After a 16-week intervention period, total cholesterol decreased 11.3% and LDL-cholesterol decreased 18.6% in the HT group, but both did not change in the soy dietary supplement and placebo groups. Values for triglycerides, HDL-cholesterol, glucose level, body mass index, blood pressure and abdominal/hip ratio did not change over time in any of the three groups.CONCLUSION: The use of dietary soy supplement did not show any significant favorable effect on cardiovascular health biomarkers compared with HT. Clinical Trial Registry: The trial is registered at the Brazilian Clinical Trials Registry (Registro Brasileiro de Ensaios Clínicos - ReBEC), number RBR-76mm75.

Efficacy of paraspinal anesthetic block in patients with chronic pelvic pain refractory to drug therapy: a randomized clinical trial

PURPOSE: To determine whether paraspinal block reduces pain scores compared to placebo in women with chronic pelvic pain refractory to drug therapy.METHODS: Subjects with chronic pelvic pain due to benign conditions and refractory to drug therapy were invited to participate in a randomized, double blind, superiority trial at a tertiary reference center. Subjects were randomly allocated to receive paraspinal anesthetic block with 1% lidocaine without epinephrine or placebo (control). Lidocaine was injected along the spinal process of the painful segment in the supra- and interspinal ligaments using a 25G X 2" needle. Placebo consisted of introduction of the needle in the same segment without injecting any substance. The main outcome measured was the pain score based on a visual analog scale at T0 (baseline), T1 (within 15 min after the procedure) and T2 (one week after the procedure). Data were statistically analyzed by ANOVA and the 95% confidence interval (95%CI).RESULTS: Mean age was similar for both groups, i.e., 51.2 (paraspinal anesthetic block) and 51.8 years (control). A blind examiner measured the degree of pain according to the visual analog scale from 0 (no pain) to 10 (worst pain imaginable). Based on the visual analog scale, the mean pain scores of the paraspinal anesthetic block group at T0, T1 and T2 were 5.50 (SD=2.92; 95%CI 3.84-7.15), 2.72 (SD=2.10; 95%CI 1.53-3.90), and 4.36 (SD=2.37; 95%CI 1.89-6.82), respectively. The difference between T0 and T1 was statistically significant, with p=0.03.CONCLUSIONS:Paraspinal anesthetic block had a small effect on visual analog scale pain score immediately after the injections, but no sustained benefit after one week. Further studies are needed to determine the efficacy of paraspinal anesthetic block with different lidocaine doses for the treatment of visceral pain of other causes.

Effectiveness of an illustrated home exercise guide on promoting urinary continence during pregnancy: a pragmatic randomized clinical trial

OBJETIVO: Avaliar a efetividade de um manual de orientação de exercícios domiciliares (MOED) para o assoalho pélvico (AP) na promoção da continência urinária em gestantes primigestas.MÉTODOS: Ensaio clínico com 87 participantes, avaliadas 6 vezes durante a gestação e divididas aleatoriamente em 3 grupos: Grupo supervisionado (Gsup), que praticou exercícios com supervisão; Grupo observado (Gobs), que praticou exercícios sem supervisão, e Grupo referência (Gref), que não praticou exercícios. Incontinência urinária (IU) (desfecho primário) e força muscular perineal (FMP) (desfecho secundário) foram avaliadas por intermédio de diário de perdas urinárias e perineometria, respectivamente. Foram utilizados o teste de Kruskal-Wallis, seguido do teste post hoc de Dunn, para variáveis contínuas, e o teste do χ2 e testes Z, com correções de Bonferroni, para proporções, com nível de significância de 5%.RESULTADOS: O Gsup e o Gobs apresentaram 6,9% de gestantes incontinentes, enquanto o Gref apresentou 96,6% de incontinentes. Quanto à FMP, o Gsup e o Gobs apresentaram valores médios de contração de 10 e 8,9 cmH2O, respectivamente, enquanto o Gref apresentou valor de 4,7 cmH2O. Ambos os resultados significantes.CONCLUSÃO: A utilização de um MOED é eficaz na promoção da continência urinária e no aumento da FMP em gestantes primigestas, independentemente de supervisão permanente.

Experimental and discrete element simulation studies of bell-less charging of blast furnace

This thesis presents an experimental study and numerical study, based on the discrete element method (DEM), of bell-less charging in the blast furnace. The numerical models are based on the microscopic interaction between the particles in the blast furnace charging process. The emphasis is put on model validation, investigating several phenomena in the charging process, and on finding factors that influence the results. The study considers and simulates size segregation in the hopper discharging process, particle flow and behavior on the chute, which is the key equipment in the charging system, using mono-size spherical particles, multi-size spheres and nonspherical particles. The behavior of the particles at the burden surface and pellet percolation into a coke layer is also studied. Small-scale experiments are used to validate the DEM models.

Chronic imipramine treatment-induced changes in acetylcholinesterase (EC 3.1.1.7) activity in discrete rat brain regions

Cholinergic as well as monoaminergic neurotransmission seems to be involved in the etiology of affective disorders. Chronic treatment with imipramine, a classical antidepressant drug, induces adaptive changes in monoaminergic neurotransmission. In order to identify possible changes in cholinergic neurotransmission we measured total, membrane-bound and soluble acetylcholinesterase (Achase) activity in several rat brain regions after chronic imipramine treatment. Changes in Achase activity would indicate alterations in acetylcholine (Ach) availability to bind to its receptors in the synaptic cleft. Male rats were treated with imipramine (20 mg/kg, ip) for 21 days, once a day. Twenty-four hours after the last dose the rats were sacrificed and homogenates from several brain regions were prepared. Membrane-bound Achase activity (nmol thiocholine formed min-1 mg protein-1) after chronic imipramine treatment was significantly decreased in the hippocampus (control = 188.8 ± 19.4, imipramine = 154.4 ± 7.5, P<0.005) and striatum (control = 850.9 ± 59.6, imipramine = 742.5 ± 34.7, P<0.005). A small increase in total Achase activity was observed in the medulla oblongata and pons. No changes in enzyme activity were detected in the thalamus or total cerebral cortex. Since the levels of Achase seem to be enhanced through the interaction between Ach and its receptors, a decrease in Achase activity may indicate decreased Ach release by the nerve endings. Therefore, our data indicate that cholinergic neurotransmission is decreased after chronic imipramine treatment which is consistent with the idea of an interaction between monoaminergic and cholinergic neurotransmission in the antidepressant effect of imipramine