Hospital Universitario Of La Princesa

Hospital de Órbigo, Spain

Hospital Universitario Of La Princesa

Hospital de Órbigo, Spain
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De Los Rios C.,Hospital Universitario Of La Princesa | De Los Rios C.,Autonomous University of Madrid
Expert Opinion on Therapeutic Patents | Year: 2012

Introduction: Cholinesterase inhibitors participate in the maintenance of the levels of the neurotransmitter acetylcholine by inhibiting the enzymes implicated in its degradation, namely, butyrylcholinesterase and acetylcholinesterase. This pharmacological action has an important role in several diseases, including neurodegenerative diseases such as Alzheimer's. Areas covered: This article reviews recent advances in the development of cholinesterase enzyme inhibitors, covering the development of new chemical entities, new pharmaceutical formulations with known inhibitors or treatments in combination with other drug families. Expert opinion: The development of cholinesterase inhibitors has to face several issues, including the fact that the principal indication for these drugs, Alzheimer's disease, is not currently believed to derivate from a cholinergic deficiency, although most of the drugs clinically used for these disease are cholinesterase inhibitors. Moreover, the adverse effects found when administering cholinesterase inhibitors limit their use in other diseases, such as gastrointestinal diseases, glaucoma, or analgesia. © 2012 Informa UK, Ltd.


Daschner A.,Hospital Universitario Of La Princesa
Frontiers in Immunology | Year: 2017

Among potential environmental harmful factors, fungi deserve special consideration. Their intrinsic ability to actively germinate or infect host tissues might determine a prominent trigger in host defense mechanisms. With the appearance of fungi in evolutionary history, other organisms had to evolve strategies to recognize and cope with them. Existing controversies around dampness and mold hypersensitivity syndrome (DMHS) can be due to the great variability of clinical symptoms but also of possible eliciting factors associated with mold and dampness. An hypothesis is presented, where an evolutionary analysis of the different response patterns seen in DMHS is able to explain the existing variability of disease patterns. Classical interpretation of immune responses and symptoms are addressed within the field of pathophysiology. The presented evolutionary analysis seeks for the ultimate causes of the vast array of symptoms in DMHS. Symptoms can be interpreted as induced by direct (toxic) actions of spores, mycotoxins, or other fungal metabolites, or on the other side by the host-initiated response, which aims to counterbalance and fight offpotentially deleterious effects or fungal infection. Further, individual susceptibility of immune reactions can confer an exaggerated response, and magnified symptoms are then explained in terms of immunopathology. IgE-mediated allergy fits well in this scenario, where individuals with an atopic predisposition suffer from an exaggerated response to mold exposure, but studies addressing why such responses have evolved and if they could be advantageous are scarce. Human history is plenty of plagues and diseases connected with mold exposure, which could explain vulnerability to mold allergy. Likewise, multiorgan symptoms in DMHS are analyzed for its possible adaptive role not only in the defense of an active infection, but also as evolved mechanisms for avoidance of potentially harmful environments in an evolutionary past or present setting. © 2017 Daschner.


Dauden E.,Hospital Universitario Of La Princesa
Journal of the European Academy of Dermatology and Venereology : JEADV | Year: 2014

Treatment non-adherence is a general challenge and a complex problem. It is a key factor that impacts the 'real-life' effectiveness of topical treatments for chronic disorders, such as psoriasis. Here, we provide our expert opinion on the real-life effectiveness of topical psoriasis treatment, using the fixed combination gel (Daivobet(®) gel; calcipotriol plus betamethasone dipropionate) as a case study. The fixed combination gel is a first-line topical treatment for mild-to-moderate psoriasis, developed to be the gold-standard therapy for psoriasis patients. This fixed combination gel is an effective and well-tolerated topical psoriasis treatment that the majority of our patients prefer to the ointment formulation. We assessed our real-life experience and considered any gaps between daily practice and clinical trials data. We recommend a multifaceted approach to improve real-life effectiveness and bridge the gap between investigational trials and treatment reality and propose the following recommendations: (1) educate primary healthcare providers on how to effectively manage topical psoriasis treatment and the patients who use the treatment; (2) educate the patient on why treatment needs to be maintained, even when symptoms improve; and (3) provide a supportive environment that will not allow the patient to feel abandoned. A patient-centric approach may improve adherence, which will lead to patients receiving more effective treatment for psoriasis. © 2014 European Academy of Dermatology and Venereology.


Gisbert J.P.,Hospital Universitario Of La Princesa | Calvet X.,University of Barcelona
Alimentary Pharmacology and Therapeutics | Year: 2011

Background: Traditional standard triple therapy for Helicobacter pylori infection (PPI-clarithromycin-amoxicillin) can easily be converted to non-bismuth quadruple (concomitant) therapy by the addition of a nitroimidazole twice daily. Aim: To critically review evidence on the role of non-bismuth quadruple therapy (PPI-clarithromycin-amoxicillin-nitroimidazole) in the treatment of H. pylori infection. Methods: Bibliographical searches were performed in MEDLINE and relevant congresses. Results: The first randomised comparison of the non-bismuth quadruple therapy and the sequential (PPI-amoxicillin 5 days plus PPI-clarithromycin-nitroimidazole 5 days) regimens recently concluded that both were similar in terms of efficacy and safety and that the sequential administration protocol may be unnecessarily complex. Several randomised controlled trials (and one meta-analysis) have demonstrated that non-bismuth quadruple therapy is more effective than and is equally well tolerated as standard triple therapy. A meta-analysis of 15 studies (1723 patients) revealed a mean H. pylori cure rate (intention-to-treat) of 90% for non-bismuth quadruple therapy. A tendency towards better results with longer treatments (7-10 days vs. 3-5 days) has been observed, so it seems reasonable to recommend the length of treatment by achieving maximal cure rates (10 days). Clarithromycin resistance may reduce the efficacy of non-bismuth quadruple therapy, although the decrease in eradication rates seems to be far lower than in standard triple therapy. Experience with the non-bismuth quadruple therapy in patients with metronidazole-resistant strains is still very limited. Conclusions: Non-bismuth quadruple (concomitant) therapy appears to be an effective, safe, and well-tolerated alternative to triple therapy and is less complex than sequential therapy. Therefore, this regimen appears well suited for use in settings where the efficacy of triple therapy is unacceptably low. © 2011 Blackwell Publishing Ltd.


Gisbert J.P.,Hospital Universitario Of La Princesa | Calvet X.,Autonomous University of Barcelona
Alimentary Pharmacology and Therapeutics | Year: 2012

Background: Even with the current most effective treatment regimens, a relevant proportion of patients will fail to eradicate Helicobacter pylori infection. Aim To evaluate the role of rifabutin in the treatment of H. pylori infection. Methods Bibliographical searches were performed in MEDLINE. Data on the efficacy of rifabutin-containing regimens on H. pylori eradication were combined and meta-analysed using the generic inverse variance method. Results Rifabutin shows good in vitro activity against H. pylori. Mean H. pylori rifabutin resistance rate (calculated from 11 studies including 2982 patients) was 1.3% (95% confidence interval = 0.9-1.7%). When only studies including patients naîve to H. pylori eradication treatment were considered, this figure was even lower (0.6%). On the other hand, higher values of rifabutin resistance were calculated (1.59%) when only post-treatment patients were considered. Overall, mean H. pylori eradication rate (intention-to-treat analysis) with rifabutin-containing regimens (1008 patients) was 73% (67-79%). Respective cure rates for second-line (223 patients), third-line (342 patients) and fourth/fifth-line (95 patients) rifabutin therapies were 79% (67-92%), 66% (55-77%) and 70% (60-79%) respectively. For treating H. pylori infection, almost all studies have administered rifabutin 300 mg/day; this dose seems to be more effective than 150 mg/day. The ideal length of treatment remains unclear, but 10- to 12-day regimens are generally recommended. The mean rate of adverse effects was 22% (19-25%). Myelotoxicity is the most significant, although this complication was rare. Until now, all patients have recovered of leucopenia uneventfully in a few days, and there have been no reports of infection or other adverse outcomes related to it. Conclusion Rifabutin-containing rescue therapy constitutes an encouraging strategy after multiple (usually three) previous eradication failures with key antibiotics such as amoxicillin, clarithromycin, metronidazole, tetracycline and levofloxacin. © 2011 Blackwell Publishing Ltd.


Gisbert J.P.,Hospital Universitario Of La Princesa
Inflammatory Bowel Diseases | Year: 2010

The aim of this article is to critically review available data regarding the safety of immunomodulators and biological therapies during pregnancy and breast-feeding in women with inflammatory bowel disease. Methotrexate and thalidomide can cause congenital anomalies and are contraindicated during pregnancy (and breast-feeding). Although thiopurines have a Food and Drug Administration (FDA) rating D, available data suggest that these drugs are safe and well tolerated during pregnancy. Although traditionally women receiving azathioprine or mercaptopurine have been discouraged from breast-feeding because of theoretical potential risks, it seems that these drugs may be safe in this scenario. Treatment with cyclosporine for steroid-refractory ulcerative colitis (UC) during pregnancy can be considered safe and effective, and the use of this drug should be considered in cases of severe UC as a means of avoiding urgent surgery. Breast-feeding is contraindicated for patients receiving cyclosporine. Biological therapies appear to be safe in pregnancy, as no increased risk of malformations has been demonstrated. Therefore, the limited clinical results available suggest that the benefits of infliximab and adalimumab in attaining response and maintaining remission in pregnant patients might outweigh the theoretical risks of drug exposure to the fetus. Stopping therapy in the third trimester may be considered, as it seems that transplacental transfer of infliximab is low prior to this. Certolizumab differs from infliximab and adalimumab in that it is a Fab fragment of an antitumor necrosis factor alpha monoclonal antibody, and therefore it may not be necessary to stop certolizumab in the third trimester. The use of infliximab is probably compatible with breast-feeding. Copyright © 2009 Crohn's & Colitis Foundation of America, Inc.


Gisbert J.P.,Hospital Universitario Of La Princesa
Gastroenterology Research and Practice | Year: 2012

Helicobacter pylori infection is the main cause of gastritis, gastroduodenal ulcer disease, and gastric cancer. After 30 years of experience in H. pylori treatment, however, the ideal regimen to treat this infection has still to be found. Nowadays, apart from having to know well first-line eradication regimens, we must also be prepared to face treatment failures. In designing a treatment strategy, we should not only focus on the results of primary therapy alone but also on the finaloveralleradication rate. The choice of a rescue treatment depends on which treatment is used initially. If a first-line clarithromycin-based regimen was used, a second-line metronidazole-based treatment (quadruple therapy) may be used afterwards, and then a levofloxacin-based combination would be a third-line rescue option. Alternatively, it has recently been suggested that levofloxacin-based rescue therapy constitutes an encouraging 2nd-line strategy, representing an alternative to quadruple therapy in patients with previous PPI-clarithromycin- amoxicillin failure, with the advantage of efficacy, simplicity and safety. In this case, quadruple regimen may be reserved as a 3rd-line rescue option. Even after two consecutive failures, several studies have demonstrated that H. pylori eradication can finally be achieved in almost all patients if several rescue therapies are consecutively given. © 2012 Javier P. Gisbert.


Gisbert J.P.,Hospital Universitario Of La Princesa | Chaparro M.,Hospital Universitario Of La Princesa
Alimentary Pharmacology and Therapeutics | Year: 2014

Background Elderly patients represent an increasing proportion of the inflammatory bowel disease (IBD) population. Aim To critically review available data regarding the care of elderly IBD patients. Methods Bibliographic searches (MEDLINE) up to June 2013. Results Approximately 10-15% of cases of IBD are diagnosed in patients aged >60 years, and 10-30% of the IBD population are aged >60 years. In the elderly, IBD is easily confused with other more common diseases, mainly diverticular disease and ischaemic colitis. The clinical features of IBD in older patients are generally similar to those in younger patients. Crohn's disease (CD) in elderly patients is characterised by its predominantly colonic localisation and uncomplicated course. Proctitis and left-sided ulcerative colitis are more common in patients aged >60 years. Infections are associated with age and account for significant mortality in IBD patients. The treatment of IBD in the elderly is generally similar. However, the therapeutic approach in the elderly should be 'start low-go slow'. The benefit of thiopurines in older CD patients remains debatable. Although the indications for anti-tumour necrosis factors in the elderly are generally similar to those for younger patients, lower response and higher adverse events have been reported in the elderly. Surgery in elderly patients does not generally differ. Ileal pouch-anal anastomosis can be successful, provided the patient retains good anal sphincter function. Conclusions Management of the older IBD patient differs from that of younger patients; therefore, conventional practice algorithms may have to be modified to account for advanced age. © 2014 John Wiley & Sons Ltd.


Dauden E.,Hospital Universitario Of La Princesa
Journal of the European Academy of Dermatology and Venereology | Year: 2011

Background The use of imiquimod for the treatment of superficial basal cell carcinoma (sBCC) in actual conditions of the daily practice has been poorly studied. Objective A prospective, observational and multicentre study was designed to gather information on the effectiveness and safety of imiquimod therapy in patients with sBCC in daily practice. Patient's satisfaction with imiquimod was also assessed. Methods A total of 370 adult patients with sBCC were included in the study. Patients were treated with imiquimod 5% cream five times per week for 6 weeks. A maximum of three lesions per patient were treated. Patients were requested to complete diary cards to register treatment-related events and had a final visit within 16 weeks after the end of treatment. Results Target sBCCs included 471 tumours, with a mean (SD) 1.3 (0.6) lesions per patient. Most sBCC were primary tumours (92.6%). Tumours were clinically diagnosed in 63.2% of cases and histologically confirmed in 36.8%. Previous sBCC had occurred in 42% of the patients. The mean number of daily applications of imiquimod was 1.0 (0.1) for a mean of 4.9 (0.5) days per week. The mean duration of treatment was 6.0 (1.0) weeks. In 13 patients (14 target sBCCs), rest periods were indicated with a mean of 5.0 (2.8) rest days. The clearance rate was 83.2%. Clearance rate was independent of the tumour size. Local skin reactions (mostly erythema) occurred in 85% of cases (mild 37%, moderate 39% and severe 24%). Nine patients discontinued imiquimod treatment because of severity of application site reactions. Most patients (82.1%) were very satisfied or satisfied with imiquimod. Conclusions The present data from a prospective study carried out in a community setting adds evidence of the usefulness and favourable clinical profile of imiquimod 5% cream when administered for treating sBCC. © 2011 European Academy of Dermatology and Venereology.


Gisbert J.P.,Hospital Universitario Of La Princesa | Calvet X.,Gastroenterology Unit
Alimentary Pharmacology and Therapeutics | Year: 2011

Background A decrease in the Helicobacter pylori eradication rate after standard triple therapy has been suggested in recent years. Aim To assess the efficacy of standard triple therapy in the eradication of H. pylori through an epidemiological analysis of all published Spanish trials. A secondary aim was to review the prevalence of clarithromycin resistance in Spain. Methods Articles on H. pylori eradication in Spain published in peer-reviewed journals were identified through MEDLINE searches. Studies that included a triple therapy consisting of any proton pump inhibitor with clarithromycin (500 mg b.d.) and amoxicillin (1 g b.d.) for up to 14 days were selected. Spanish studies evaluating the prevalence of clarithromycin resistance were also reviewed. Meta-analysis was performed using the generic inverse variance method. Results The pooled eradication rates by year from Spanish studies evaluating the efficacy of the standard triple regimen revealed a relatively constant rate over the years. Overall, the analysis of the 32 studies (4727 patients) showed a mean H. pylori cure rate of 80% (95% CI = 77-82%) by intention-to-treat and 83% (81-86%) by per-protocol. When only peptic ulcer disease or 7-day regimens were considered, results were similar. Based on 13 studies (3293 patients), mean clarithromycin resistance rate was 8% (5-10%). Conclusion Although a decrease in the H. pylori eradication rate after triple therapy has been suggested in recent years, cure rates with this regimen did not change in Spain between 1997 and 2008. However, this by no means indicates that the efficacy of standard triple therapy in Spain is acceptable, as it has been calculated to be around only 80%. Therefore, it is evident that new strategies to improve first-line treatment are urgently needed. © 2011 Blackwell Publishing Ltd.

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