La Princesa Research Articles

Current trends in the treatment of H. pylori infection in Ukraine: results of the European Registry on Helicobacter pylori Management (Hp EuReg)

Current trends in the treatment of H. pylori infection in Ukraine: results of the European Registry on Helicobacter pylori Management (Hp EuReg)
 The European Registry on Helicobacter pylori Management (Hp EuReg) was established to evaluate the efficacy and safety of the different eradication H. pylori treatments, as well as to audit H. pylori infection consensus and clinical guidelines implementation. The current study presents data from a sample of patients from Ukraine who were registered in the Hp EuReg until February 2022.
 The aim was to assess the frequency, effectiveness and safety of treatment against H. pylori infection in Ukraine.
 Materials and methods. The Hp EuReg, an international multicenter prospective non‑interventional registry, was launched in 2013 and is promoted by the European Helicobacter and Microbiota Study Group (www.helicobacter.org). The Hp EuReg protocol was approved by the Ethics Committee of La Princesa University Hospital (Madrid, Spain) and registered with Clinical Trials.gov under the code NCT02328131. The effectiveness analysis included mainly a modified intention‑to‑treat (mITT) analysis, aiming to mimic the clinical practice outcomes and including all records with a confirmatory test after the eradication treatment, regardless of compliance. Given that some treatment regimens were used only in a small number of patients, only regimens with a relevant number of patients were selected for analyses.
 Results. Overall 841 patients (54 % women, 46 % men), whose average age (SD) was 48.35 (± 15.52) were included in the register. The main method for diagnosing on‑going H. pylori infection was histology, and the use of urea breath tests and stool antigen tests was low — (approximately 6 % of cases). Assessment of bacterial antibiotic resistance was performed in 13 % of patients, with less than 1 % reporting a positive result. More than half of the patients received quadruple therapy and 40 % triple therapy. Over 90 % of patients were treatment‑ naïve. Almost all patients received low‑dose proton pump inhibitors (PPIs), and a smaller proportion received standard (7.2 %) or high‑dose PPIs (1.2 %). Low‑doses PPI prescriptions negatively affected the effectiveness of therapy: in treatment‑naïve patients’ overall effectiveness was below 85 %, while the use of standard‑ and high‑doses of PPIs achieved 100 % eradication rates in all patients. Despite the fact that the duration of therapy in the vast majority of patients was at least prescribed for 10 days, there were cases (12 %) of administration of 7‑day therapy with the reported suboptimal (< 90 %) effectiveness. In those prescribed with a first‑line treatment of 7 — 10 days, the eradication rate was 82 %, while therapy for 14 days provided 100 % treatment eradication success. In the overall mITT analysis, the use of therapy in naïve patients resulted in the eradication of H. pylori in more than 90 % of patients. It is noteworthy that effectiveness with PPI+ amoxicillin + levofloxacin was below 84 %, suboptimal according to the most up‑to‑date consensus. The administered therapy was well tolerated, which allowed to complete the treatment of more than 90 % of patients, and the incidence of adverse events was less than 4 % in naïve patients, while in patients with repeated courses of therapy it was more than 3 times higher.
 Conclusions. In Ukraine, the frequency of use of validated non‑invasive methods (urea breath tests and stool antigen test) to detect H. pylori infection is very low. However, Ukrainian doctors often use methods to assess the antibiotic resistance of Helicobacter pylori, which certainly helps to increase the rate of therapy‑guided eradication. The vast majority of eradication therapies administered to patients in the Ukrainian population corresponds to the current guidelines, but very often PPIs were administered in low doses and there were still some cases of regimens lasting 7 days, even in those patients receiving a second‑line therapy, which reduced the treatment effectiveness. Even though overall effectiveness of eradication therapy was over 90 %., there is a need to closely monitor treatment management. Prescribed first‑line therapy was well tolerated by patients — more than 98 % of patients completed treatment.

Utility of a Laboratory Alert System for Detecting Adverse Drug Reactions in Hospitalised Patients: Hyponatremia and Rhabdomyolysis.

Background—Adverse drug reactions (ADRs) are a public health issue, due to their great impact on morbidity, mortality, and economic cost. The use of automatized laboratory alerts could simplify greatly its detection. Objectives—We aimed to evaluate the performance of a laboratory alerts system as a method for detecting ADRs, using hyponatremia and rhabdomyolysis as case studies. Methods—This is a retrospective observational study conducted in 2019 during a 6-month period, including patients hospitalized at the Hospital Universitario de La Princesa. Patients were identified using altered laboratory parameters corresponding to the two signals: “rhabdomyolysis” (creatine phosphokinase >5 times the upper limit of normality (ULN): >1000 U/L for men and >900 U/L for women) and “hyponatremia” (<116 mEq/L) were detected. In cases where ADR was suspected, causality assessment was performed using the algorithm of the Spanish Pharmacovigilance System (SEFV). Results—During the study period, 180 patients were studied for the “rhabdomyolysis” signal, 6 of them were found to have an ADR (3.3%). The sensitivity of the test was 60%, specificity 97%, and positive predictive value 41%. 28 patients were studied for the “hyponatremia” signal, and 11 patients were found to have an ADR (39.3%), with a sensitivity of 76.9%, a specificity of 93.3%, and a positive predictive value of 88.2%. We found no relationship between altered laboratory values and risk of ADR in any of the cases studied. Conclusion—A pharmacovigilance program based on automatized laboratory signals could be an effective method to detect ADR. The study of the “hyponatremia” laboratory alert is more efficient than “rhabdomyolysis”. The evaluation of the hyponatremia alert allows the identification of 12 times more ADRs than the rhabdomyolysis alert, which means less time spent per alert evaluated to identify an ADR.

Disability and Fatigue in Multiple Sclerosis: Can Rehabilitation Improve Them through a Structured Retraining Program?

Functional rehabilitation programs in multiple sclerosis have demonstrated their efficacy in improving fatigue. The assessment of functional impairment, however, is more difficult. The purpose is to assess fatigue and disability as a first study measure and to verify their improvement after a specific functional rehabilitation program. An analytical, longitudinal, prospective, and experimental study was carried out with 51 patients aged 18-55 years, with an Expanded Disability Status Scale (EDSS) between 2 and 6.5 who were being followed up in outpatient clinics of the Rehabilitation Service of La Princesa Hospital. The fatigue and disability outcomes before and after a structured exercise training program were evaluated, with each subject acting as their own control. The variables were measured using the Modified Fatigue Impact Scale (MFIS), Barthel Index (BI), and Functional Independence Scale (FIM). Differences according to recurrent or progressive course of the disease are assessed. Improvement in the FIM scale was observed after the retraining program (p = 0.016) and was maintained in the medium term (p = 0.042). This improvement is not statistically significant in Barthel Index. Improvement in MFIS is observed after the program (p < 0.001) and 4-6 months after the end. Both disease courses experience the same improvements with no statistically significant differences between them. The retraining program improves fatigue and multiple sclerosis-related functionality in the short and medium term. There are no differences according to disease course. Both experience the same positive changes with our intervention.

SARS-CoV-2 Viremia Precedes an IL6 Response in Severe COVID-19 Patients: Results of a Longitudinal Prospective Cohort.

BackgroundInterleukin 6 (IL6) levels and SARS-CoV-2 viremia have been correlated with COVID-19 severity. The association over time between them has not been assessed in a prospective cohort. Our aim was to evaluate the relationship between SARS-CoV-2 viremia and time evolution of IL6 levels in a COVID-19 prospective cohort.MethodsSecondary analysis from a prospective cohort including COVID-19 hospitalized patients from Hospital Universitario La Princesa between November 2020 and January 2021. Serial plasma samples were collected from admission until discharge. Viral load was quantified by Real-Time Polymerase Chain Reaction and IL6 levels with an enzyme immunoassay. To represent the evolution over time of both variables we used the graphic command twoway of Stata.ResultsA total of 57 patients were recruited, with median age of 63 years (IQR [53–81]), 61.4% male and 68.4% Caucasian. The peak of viremia appeared shortly after symptom onset in patients with persistent viremia (more than 1 sample with > 1.3 log10 copies/ml) and also in those with at least one IL6 > 30 pg/ml, followed by a progressive increase in IL6 around 10 days later. Persistent viremia in the first week of hospitalization was associated with higher levels of IL6. Both IL6 and SARS-CoV-2 viral load were higher in males, with a quicker increase with age.ConclusionIn those patients with worse outcomes, an early peak of SARS-CoV-2 viral load precedes an increase in IL6 levels. Monitoring SARS-CoV-2 viral load during the first week after symptom onset may be helpful to predict disease severity in COVID-19 patients.

Transmembrane protease serine 2 (TMPRSS2) rs75603675, comorbidity, and sex are the primary predictors of COVID-19 severity.

By the end of December 2021, coronavirus disease 2019 (COVID-19) produced more than 271 million cases and 5.3 million deaths. Although vaccination is an effective strategy for pandemic control, it is not yet equally available in all countries. Therefore, identification of prognostic biomarkers remains crucial to manage COVID-19 patients. The aim of this study was to evaluate predictors of COVID-19 severity previously proposed. Clinical and demographic characteristics and 120 single-nucleotide polymorphisms were analyzed from 817 patients with COVID-19, who attended the emergency department of the Hospital Universitario de La Princesa during March and April 2020. The main outcome was a modified version of the 7-point World Health Organization (WHO) COVID-19 severity scale (WHOCS); both in the moment of the first hospital examination (WHOCS-1) and of the severest WHOCS score (WHOCS-2). The TMPRSS2 rs75603675 genotype (OR = 0.586), dyslipidemia (OR = 2.289), sex (OR = 0.586), and the Charlson Comorbidity Index (OR = 1.126) were identified as the main predictors of disease severity. Consequently, these variables might influence COVID-19 severity and could be used as predictors of disease development.

Secukinumab is effective in the treatment of recalcitrant palmoplantar psoriasis and palmoplantar pustular psoriasis in a daily practice setting

Secukinumab is effective in the treatment of recalcitrant palmoplantar psoriasis and palmoplantar pustular psoriasis in a daily practice setting

Redefining Truths: Manuela Rosas as a subject of Imaginative Reconstruction in the Argentine Literary Realm

Manuela Rosas, the daughter of Federalist dictator Juan Manuel de Rosas, is an important nineteenth century political figure who was a consistent subject of imaginative reconstruction during the Rosas era. Much like her fellow women revolutionaries, namely Eva Perón and her mother, Encarnación Ezcurra de Rosas, Manuela assumed an active role in the Argentine political arena and was instrumental maintaining her father’s unparalleled political supremacy, acting as chief mediator between the government and the marginalised Argentine masses. This article argues how, in a series of nineteenth-century fictional works, namely those of renowned Unitarians José Mármol (Amalia; El retrato de Manuela Rosas, 1851) and Juana Manuela Gorriti (El guante negro; La hiza del mashorquero, 1865), Manuela has been inaccurately depicted as ‘la primera victíma de la tiranía de su padre’ who desperately needed rescuing. Both writers maintain that Rosas curtailed his daughter’s social freedom, and that she would have reached her true potential had she been raised by civilised Unitarians and not in a Federalist environment. However, María Rosa Lojo’s La princesa federal (2010) contests the claim that Manuela suffered, instead postulating that she was a resilient and empowered individual who was passionate about promoting the causa federalista, remaining loyal to her father out of choice. I offer an original critical analysis of the unacknowledged and divergent literary and historical representations of Manuela, examining how writers use the lack of historical evidence to manipulate and imaginatively reconstruct her life story and in doing so, blur the line between fact and fiction.

Redefining Truths: Manuela Rosas as a subject of Imaginative Reconstruction in the Argentine Literary Realm

Manuela Rosas, the daughter of Federalist dictator Juan Manuel de Rosas, is an important nineteenth century political figure who was a consistent subject of imaginative reconstruction during the Rosas era. Much like her fellow women revolutionaries, namely Eva Perón and her mother, Encarnación Ezcurra de Rosas, Manuela assumed an active role in the Argentine political arena and was instrumental maintaining her father’s unparalleled political supremacy, acting as chief mediator between the government and the marginalised Argentine masses. This article argues how, in a series of nineteenth-century fictional works, namely those of renowned Unitarians José Mármol (Amalia; El retrato de Manuela Rosas, 1851) and Juana Manuela Gorriti (El guante negro; La hiza del mashorquero, 1865), Manuela has been inaccurately depicted as ‘la primera victíma de la tiranía de su padre’ who desperately needed rescuing. Both writers maintain that Rosas curtailed his daughter’s social freedom, and that she would have reached her true potential had she been raised by civilised Unitarians and not in a Federalist environment. However, María Rosa Lojo’s La princesa federal (2010) contests the claim that Manuela suffered, instead postulating that she was a resilient and empowered individual who was passionate about promoting the causa federalista, remaining loyal to her father out of choice. I offer an original critical analysis of the unacknowledged and divergent literary and historical representations of Manuela, examining how writers use the lack of historical evidence to manipulate and imaginatively reconstruct her life story and in doing so, blur the line between fact and fiction

Genotype-Guided Prescription of Azathioprine Reduces the Incidence of Adverse Drug Reactions in TPMT Intermediate Metabolizers to a Similar Incidence as Normal Metabolizers.

IntroductionThiopurine drugs are purine nucleoside analogues used for treatment of different immune-related conditions. To date, different studies highlighted the importance of thiopurine methyltransferase (TPMT) genotyping in patients who initiate treatment with thiopurines to make an adequate dose adjustment. We aimed to investigate the influence of TPMT phenotype, concomitant treatments, and demographic characteristics on the incidence of adverse reactions (ADRs) in patients who start treatment with azathioprine (AZA).MethodsThis was an observational and retrospective study. The study population comprised 109 patients who started treatment with AZA following routine TPMT genotyping before June 2019 and who were routinely followed up at Hospital Universitario de La Princesa. The incidence of ADRs and treatment duration were evaluated according to TPMT phenotype.ResultsForty-five men and 64 women were recruited, with a mean age of 67.6 ± 18.5. The medical specialty with the most requests was dermatology (45.9%) and the most frequent disease for which genotyping was requested was bullous pemphigoid (27.5%). All patients were normal metabolizers (NM), except for eight intermediate metabolizers (IM) (7.3%); no poor metabolizers (PM) were found. The initial azathioprine dose was subtherapeutic in both groups (103.2 ± 45.4 mg in NMs and 75 ± 32.3 mg in IMs), increasing during the first months of treatment, especially in NMs (120.3 ± 41.3 vs. 78.6 ± 30.4 mg in IMs, p = 0.011). Most patients (73.4%) received corticosteroids to keep the disease under control; and for 41.2% of NMs, physicians were able to reduce the dose at 6 months post treatment. No IMs completed 6 months of treatment. Hepatotoxicity, gastric intolerance, and blood disorders were the most common ADRs. The incidence of ADRs in the sample was 28.4% (n = 31) with a similar trend between IMs (37.5%) and NMs (27.8%). Patients undergoing concomitant treatment with allopurinol were associated with a higher incidence of ADRs (n = 4, 100% vs. n = 105, 20%; p = 0.002).ConclusionTPMT genotyping before AZA prescription reduces ADR incidence in IMs to a similar level as NMs in the Spanish population. However, it is important to note no IMs completed 6 months of treatment, suggesting that there may be some differences in drug tolerability according to phenotype. In addition, most NMs are treated with subtherapeutic doses, are poorly followed up, and thus suffer avoidable ADRs. Finally, concomitant therapies that inhibit the xanthine oxidase enzyme (XDH), such as allopurinol, predispose to ADRs. Therefore, pharmacogenetic testing should be integrated as an additional clinical tool, in such a way that each patient receives personalized, precision treatment, where all factors influencing drug response are considered.

HP37: Critical illness polyneuropathy in COVID-19 patients: A case-control study

Introduction: The coronavirus SARS CoV-2 (COVID-19) could cause damage to neural tissue. This injury is responsible for neuromuscular disturbance after the onset of respiratory symptoms in these patients.Objective: is to analyze the characteristics of all patients diagnosed with critical illness polyneuropathy (CIP) reported from March 2020 to March 2021 in the Clinical Neurophysiology Department from La Princesa University Hospital.Methods: Patients were classified into two groups 17 patients admitted to the hospital with confirmed COVID-19 (Cases Group, CaG) and 12 patients without COVID-19 infection (Control Group, CoG). We performed both electroneurography and electromyography.Results: The distribution of the subtypes of the CIP was as follows: axonal motor polyneuropathy (24% in CaG vs 25% in CoG), axonal sensorimotor polyneuropathy (35% in CaG vs 58% in CoG), and mixed sensorimotor polyneuropathy (41% in CaG vs 16% in CoG).Needle EMG showed spontaneous activity in 100% in CaG vs 75% in CoG. The days of hospitalisation were 64.8 ± 7.9 in the CaG and 54.5 ± 9.9 in the CoG. Favourable evolution was observed in the 35% in CaG vs 42% in CoG, and unfavourable evolution was observed in the 41% in CaG vs 33% in CoG.Conclusion: We highlighted the nerves damaged in patients infected by COVID-19 and admitted to the Intensive Care Unit. Viral neuropathy is thought to be primarily axonal; however, we observe a high prevalence of demyelinating injuries in patients affected with this infection. Considering these results, we focus on the importance of early neurorehabilitation to improve nerve function.

Patients' Perceptions of Pharmacogenetic Testing and Access to Their Results: State of the Art in Spain and Systematic Review.

The process of clinical pharmacogenetics implementation depends on patients’ and general population’s perceptions. To date, no study has been published addressing Spanish patients’ opinions on pharmacogenetic testing, the availability of the results, and the need for signing informed consent. In this work, we contacted 146 patients that had been previously genotyped at our laboratory and 46 healthy volunteers that had participated in a bioequivalence clinical trial at the Clinical Pharmacology Department of Hospital Universitario de La Princesa and consented to pharmacogenetic testing for research purposes. From the latter, 108 and 34, respectively, responded to the questionnaire (i.e., a response rate of 74%); Participants were scheduled for a face-to-face, telephone, or videoconference interview and were asked a total of 27 questions in Spanish. Great or almost complete acceptance of pharmacogenetic testing was observed (99.3%), age and university education level being the main predictors of acceptance rates and understanding (multivariate analysis, p = 0.004, R2 = 0.17, age being inversely proportional to acceptance rates and understanding and university level being related to higher acceptance rates and understanding compared to other education levels). Mixed perceptions were observed on the requirement of written informed consent (55.6% in favor); therefore, it seems recommendable to continue requesting it for the upcoming years until more perceptions are collected. The majority of participants (95.8%) preferred storing pharmacogenetic results in medical records rather than in electronic sources (55.6%) and highly agreed with the possibility of carrying their results on a portable card (91.5%). Patients agreed to broad genetic testing, including biomarkers unrelated to their disease (93.7%) or with little clinically relevant evidence (94.4%). Patients apparently rely on clinician’s or pharmacogeneticist’s interpretation and seem, therefore, open to the generation of ethically challenging information. Finally, although most patients (68.3%) agreed with universal population testing, some were reluctant, probably due to the related costs and sustainability of the Spanish Health System. This was especially evident in the group of patients who were older and with a likely higher proportion of pensioners.

Revolution and Power in Puerto Rican Nonfiction

Revolution and Power in Puerto Rican Nonfiction

Sepsis Code: dodging mortality in a tertiary hospital

IntroducciónEn el hospital de La Princesa comienza el “Código Sepsis” (CSP) en el año 2015, como un grupo multidisciplinar que dota al personal sanitario de herramientas clínicas, analíticas y organizativas, con el objetivo de la detección y el tratamiento precoz del paciente con sepsis. El objetivo de este estudio es evaluar el impacto de la implantación de CSP en la mortalidad y determinar las variables asociadas con un aumento de la misma.Material y métodosSe realizó un estudio analítico retrospectivo de los pacientes con activación de la alerta CSP de 2015 a 2018. Se recogieron variables clínico-epidemiológicas, parámetros analíticos y factores de gravedad como el ingreso en Unidades de Cuidados Críticos (UCC) y la necesidad de aminas. La significación estadística se estableció en una p < 0,05.ResultadosSe incluyeron 1.121 pacientes. La estancia media fue de 16 días y un 32% requirieron ingreso en UCC. La mortalidad mostró una tendencia lineal descendente estadísticamente significativa del 24% en 2015 hasta el 15% en 2018. Las variables predictivas de mortalidad con asociación estadísticamente significativa fueron el lactato > 2 mmol/L, la creatinina > 1,6 mg/dL y la necesidad de aminas.ConclusionesLa implementación de Código Sepsis disminuye la mortalidad de los pacientes con sepsis y shock séptico. La presencia de una cifra de lactato > 2 mmol/L, los niveles de creatinina > 1,6 mg/dL y/o la necesidad de administrar aminas en las primeras 24 horas, se asocian con un aumento de la mortalidad en el paciente con sepsis.

Intense Impact of Health Alert Due to COVID-19 on Adherence of Moderate to Severe Psoriasis Patients to Hospital Therapy

Background: Psoriasis is a chronic skin disease in which lifelong treatment is required. Recently, we faced COVID-19 pandemic where adherence to a prescribed drug could have been affected. Objectives: We conduct a study to assess this statement. Methods: The study was performed in Dermatology Department with Pharmacy database in the Hospital Universitario de La Princesa. A retrospective observational database study was performed, including all psoriatic patients with a biological therapy prescription between March 13 and May 31, 2020, with a paired control group between March 13 and May 31, 2019. Medication possession ratio (MPR) was used to determine the adherence. Results: A total of 244 patients were included in the cohort and 228 in the control group. We observed a decrease in the percentage of adherent patients of 40.0% in COVID-19 period. Overall, MPR was lower in the 2020 period than in 2019. MPRs by treatment and drug family, with the exception of etanercept, certolizumab pegol, and guselkumab, were significantly lower between the 2019 and the 2020 period. Conclusions: Adherence to a prescribed drug can be affected by different factors such as age, sex, income quintile, or stress. We have demonstrated a deep impact on adherence because of the situation created by COVID-19 pandemic. These data are in contrast with previously reported results where adherence was slightly affected, probably due to the different epidemiological situation in different countries. Further efforts are needed to be done to mitigate COVID-19 pandemic influence on the therapeutic adherence.

24-month Real-World Study of Spinal Cord Stimulation in Failed Back Surgery Patients with Refractory Pain

Failed Back Surgery Syndrome (FBSS) causes disability and lowers health-related quality of life (HRQoL) for patients. Many patients become refractory to Conventional Medical Management (CMM) and Spinal Cord Stimulation (SCS) is advised. However, comparative effectiveness research of both clinical approaches still lacks further evidence. This study describes Comparative Effectiveness Research of CMM versus SCS to provide real world evidence regarding the appropriate means for FBSS management, in terms of Patient-Reported Outcomes Measures. Naturalistic, pragmatic, prospective observational multicenter SEFUDOCE-study. FBSS patients attending clinical programmed visits in Pain Unit at Hospital Universitario de La Princesa and at Hospital General Universitario de Alicante (Spain). Study evaluates the impact on pain, functional limitation, and HRQoL of CMM versus SCS in the management of FBSS. Patients completed Pain Detect Questionnaire, Oswestry Disability Index, EQ-5D-3L, Medical Outcomes Study Sleep Scale, and Hospital Anxiety and Depression Scale at baseline and at 3, 6, 12, 18 and 24 months. Longitudinal data were analysed with repeated-measures one-way analysis of variance adjusting by confounders. Eighty-five adults patients with FBSS receiving treatment according to current clinical practice were assessed. After 24 months, the PainDETECT Questionnnaire showed that CMM patients maintained similar scores, while SCS patients reduced their overall score (current pain: 6 CMM versus 4.21 SCS, P = 0.0091; intensity strongest pain: 7.77 CMM versus 6.07 SCS, P = 0.0103; average pain: 6.46 CMM versus 4.75 SCS, P = 0.0012). For the Oswestry Disability Index, the Medical Outcomes Study Sleep Scale, and the Hospital Anxiety and Depression Scale no significant inter-group differences were found. EQ-5D utility improved in SCS patients from baseline (baseline: 0.32 CMM versus 0.22 SCS; 24-month: 0.37 CMM versus 0.63 SCS, P = 0.026). Twenty-four month follow-up showed unlikely presence of neuropathic pain and moderate disability in SCS patients, whereas the CMM patients maintained baseline health state. Given the nature of the intervention, conducting a blinded study was not considered practically feasible. A larger sample could also overcome having younger patients in the SCS arm. SCS may improve the HRQoL and functionality of FBSS patients with refractory pain in the long-term compared to CMM alone.

PriME-PGx: La Princesa University Hospital Multidisciplinary Initiative for the Implementation of Pharmacogenetics

The implementation of clinical pharmacogenetics in daily practice is limited for various reasons. Today, however, it is a discipline in full expansion. Accordingly, in the recent times, several initiatives promoted its implementation, mainly in the United States but also in Europe. In this document, the genotyping results since the establishment of our Pharmacogenetics Unit in 2006 are described, as well as the historical implementation process that was carried out since then. Finally, this progress justified the constitution of La Princesa University Hospital Multidisciplinary Initiative for the Implementation of Pharmacogenetics (PriME-PGx), promoted by the Clinical Pharmacology Department of Hospital Universitario de La Princesa (Madrid, Spain). Here, we present the initiative along with the two first ongoing projects: the PROFILE project, which promotes modernization of pharmacogenetic reporting (i.e., from classic gene-drug pair reporting to complete pharmacogenetic reporting or the creation of pharmacogenetic profiles specific to the Hospital’s departments) and the GENOTRIAL project, which promotes the communication of relevant pharmacogenetic findings to any healthy volunteer participating in any bioequivalence clinical trial at the Clinical Trials Unit of Hospital Universitario de La Princesa (UECHUP).

Deep Brain Stimulation of the Nucleus Accumbens, Ventral Striatum, or Internal Capsule Targets for Medication-Resistant Obsessive-Compulsive Disorder: A Multicenter Study

Deep brain stimulation of the nucleus accumbens, ventral striatum, or internal capsule region has shown a 45%-60% response rate in adults with severe treatment-refractory obsessive-compulsive disorder, regardless of which target is used. We sought to improve the effectiveness of deep brain stimulation by placing the electrode along a trajectory including these 3 targets, enabling a change of stimulation site depending on the patient's response. This study used the medical records of 14 patients from 4 different Spanish institutions: 7 from the Hospital Universitario La Princesa, 3 from the Hospital Universitario Central de Asturias, 2 from Hospital Universitario Fundación Jiménez Díaz, and 2 from Hospital Universitari Son Espases. All patients were operated on under the same protocol. Qualitative and quantitative data were collected. Of 14 patients, 11 showed significant improvement in obsessive-compulsive disorder symptoms, as evident in a reduction ≥35% in Yale-Brown Obsessive Compulsive Scale scores following stimulation relative to preoperative scores. Seven patients responded to stimulation at the nucleus accumbens (the first area we set for stimulation), whereas 4 patients needed to have the active contact switched to the internal capsule to benefit from stimulation. Deep brain stimulation of the nucleus accumbens, internal capsule, and ventral striatum significantly benefited our cohort of patients with medication-resistant obsessive-compulsive disorder. Electrode insertion through the 3 main targets might confer additional therapeutic efficacy.

Development and Validation of the OSA-CPAP Perceived Competence Evaluation Interview

IntroductionContinuous positive airway pressure (CPAP) is one of the most common therapies for Obstructive Sleep Apnea (OSA). We present a brief, patient-reported outcome measure used to assess patients’ levels of adherence with CPAP treatment. MethodsA questionnaire was developed based on academic literature. We qualitatively tested a pool of 18 items. It was tested in a sample of 174 patients from the Hospital La Princesa. Next, 1021 patients from Catalonia were evaluated. Results5 items were removed. Nominal groups referred to three areas: general knowledge about OSA and its risks; CPAP treatment information and expectations; CPAP use, monitoring, and confidence with its use. The 13 retained items maintained the same meaning as the original questionnaire (r=.986; p<.001) and the three proposed dimensions detected a significant increase in general knowledge of OSA (t[173]=8.097, p<.001); CPAP treatment information (t[173]=15.170, p<.001); and CPAP use (t[173]=14.642, p<.001). The final 12-item version was reliable (CRI=.793) and its internal structure was adequate (χ2[51]=72.073; p=.027, CFI=.967, RMSEA=.020 [.000, .030]). Women had a better general knowledge of OSA (t[1,018]=2.190, p=.029), CPAP treatment information (t[1,018]=2.920, p=.004), and higher overall OSA-CPAP scores (t[1,018]=3.093, p=.002). Scores were positively related to quality of life and motivation, adherence was positively related to CPAP use and monitoring, and the total score was negatively related to daytime sleepiness. ConclusionsThe interview could help clinicians prevent some dropouts by targeting patients with lower adherence. It's a tool for assessing patient adherence to CPAP and to promote strategies through education and external motivational stimuli.

Disease Activity Indices in Rheumatoid Arthritis: Comparative Performance to Detect Changes in Function, IL-6 Levels, and Radiographic Progression.

Objective: To compare the capacity of various disease activity indices to evaluate changes in function, IL-6 levels, and radiographic progression in early and established rheumatoid arthritis (RA).Methods: Secondary data analysis of a clinical trial assessing the efficacy of tocilizumab in patients with established RA (ACT-RAY) and a longitudinal prospective register of early arthritis (PEARL). Targeted outcomes were changes in physical function, measured with the health assessment questionnaire (HAQ), IL-6 serum levels, and radiographic progression. The “Hospital Universitario La Princesa Index” (HUPI), DAS28 using erythrocyte sedimentation rate and SDAI were the disease activity indices compared. Models adjusted for age and sex were fitted for each outcome and index and ranked based on the R2 parameter and the quasi-likelihood under the independence model criterion.Results: Data from 8,090 visits (550 patients) from ACT-RAY and 775 visits (534 patients) from PEARL were analyzed. The best performing models for HAQ were the HUPI (R2 = 0.351) and SDAI ones (R2 = 0.329). For serum IL-6 levels, the SDAI (R2 = 0.208) followed by the HUPI model (R2 = 0.205). For radiographic progression in ACT-RAY, the HUPI (R2 = 0.034) and the DAS28 models (R2 = 0.026) performed best whereas the DAS28 (R2 = 0.030) and HUPI models (R2 = 0.023) did so in PEARL.Conclusions: HUPI outperformed other indices identifying changes in HAQ and radiographic progression and performed similarly to SDAI for IL-6 serum levels.

Sustained-release isosorbide mononitrate as adjuvant treatment in isolated systolic hypertension in the elderly.

Hypertension is one of the main cardiovascular risk factors. In the elderly, the most common form is isolated systolic hypertension, a consequence of the increase in arterial stiffness. None of the antihypertensives currently used affects arterial stiffness, whereas nitrates seem to have an effect. The aim of this work was to assess their effect on elderly patients with uncontrolled isolated systolic hypertension, defined as systolic blood pressure over 140 mmHg and diastolic blood pressure under 90 mmHg. The present study is a phase III, randomized, multicenter, double-blind, placebo-controlled clinical trial, conducted at the University Hospital La Princesa in Madrid. Patients of both sexes, aged 65 years or older, with poorly controlled isolated systolic hypertension, were treated with 40-60 mg of sustained-release isosorbide mononitrate or matching placebo for 12 weeks. The main objective was to assess the effect on clinical pulse pressure (PP); in addition, its effect on vascular function was evaluated. Analysis was performed by intention to treat. The study was registered at the European Union Clinical Trials Register (EUDRACT 2012-002988-10) and was funded by the Spanish Ministry of Health. A total of 58 patients with an average age of 77 years were enrolled, 32 were treated with nitrate, and 26 with placebo. No significant differences were found either in PP decline (5.28 vs 7.49 mmHg, p = 0.79) or in other variables, including parameters of vascular function. There were no differences in adverse events. The results of this study have not confirmed the benefit of nitrate treatment in isolated systolic hypertension or the improvement of vascular function.