Showing papers by "Hospital General Universitario Gregorio Marañón published in 2011"

Diagnosis and management of oropharyngeal dysphagia and its nutritional and respiratory complications in the elderly

Abstract: Oropharyngeal dysphagia is a major complaint among older people. Dysphagia may cause two types of complications in these patients: (a) a decrease in the efficacy of deglutition leading to malnutrition and dehydration, (b) a decrease in deglutition safety, leading to tracheobronchial aspiration which results in aspiration pneumonia and can lead to death. Clinical screening methods should be used to identify older people with oropharyngeal dysphagia and to identify those patients who are at risk of aspiration. Videofluoroscopy (VFS) is the gold standard to study the oral and pharyngeal mechanisms of dysphagia in older patients. Up to 30% of older patients with dysphagia present aspiration—half of them without cough, and 45%, oropharyngeal residue; and 55% older patients with dysphagia are at risk of malnutrition. Treatment with dietetic changes in bolus volume and viscosity, as well as rehabilitation procedures can improve deglutition and prevent nutritional and respiratory complications in older patients. Diagnosis and management of oropharyngeal dysphagia need a multidisciplinary approach.

Single nucleotide polymorphism associations with response and toxic effects in patients with advanced renal-cell carcinoma treated with first-line sunitinib: a multicentre, observational, prospective study

Abstract: Summary Background Sunitinib is a tyrosine kinase inhibitor with proven efficacy in renal-cell carcinoma, but some patients do not respond or need dose reductions due to toxicity. Because there are no validated molecular predictors of response or toxicity to sunitinib, we aimed to identify genetic markers predictive of outcome and toxic effects. Methods In our observational, prospective study we enrolled previously untreated adults (≥18 years) with clear-cell renal-cell carcinoma at 15 institutions in the Spanish Oncology Genitourinary Group in Spain. Patients received sunitinib according to local practice guidelines. We assessed RECIST response, progression-free survival (PFS), overall survival, and toxicity of sunitinib with 16 key polymorphisms in nine genes: VEGFR2 (rs2305948 and rs1870377), VEGFR3 (rs307826, rs448012, and rs307821), PDGFR -α (rs35597368), VEGF-A (rs2010963, rs699947, and rs1570360), IL8 (rs1126647), CYP3A4 (rs2740574), CYP3A5 (rs776746), ABCB1 (rs1045642, rs1128503, and rs2032582), and ABCB2 (rs2231142). We assessed associations with efficacy and toxicity by use of univariable and multivariable analyses (with clinical factors associated with outcomes as covariates). We adjusted for multiplicity using the Bonferroni method; p values of less than 0·0031 before adjustment were deemed to still be significant after adjustment. Findings We enrolled 101 patients between Oct 10, 2007, and Dec 13, 2010. 95 of these patients were included in toxicity analyses and 89 in the efficacy analyses. Two VEGFR3 missense polymorphisms were associated with reduced PFS with sunitinib on multivariable analysis: rs307826 (hazard ratio [HR] per allele 3·57, 1·75–7·30; p unadjusted =0·00049, p adjusted =0·0079) and rs307821 (3·31, 1·64–6·68; p unadjusted =0·00085, p adjusted =0·014). The CYP3A5*1 (rs776746) high metabolising allele was associated in a multivariable analysis with an increased risk of dose reductions due to toxicity (HR per allele 3·75, 1·67–8·41; p unadjusted =0·0014, p adjusted =0·022). No other SNPs were associated with sunitinib response or toxicity. Interpretation Polymorphisms in VEGFR3 and CYP3A5*1 might be able to define a subset of patients with renal-cell carcinoma with decreased sunitinib response and tolerability. If confirmed, these results should promote interventional studies testing alternative therapeutic approaches for patients with such variants. Funding Pfizer.

Causes and effects of surgical delay in patients with hip fracture: a cohort study.

Abstract: Background The clinical effect of surgical delay in older patients with hip fracture is controversial. Discrepancies among study findings may be due to confounding that is caused by the reason for the delay or a differential effect on patient risk subgroups. Objective To assess the effect of surgical delay on hospital outcomes according to the cause of delay. Design Prospective cohort study. Setting A hip fracture unit in a university hospital in Spain. Patients 2250 consecutive elderly patients with hip fracture. Measurements Time to surgery, reasons for surgical delay, adjusted in-hospital death, and risk for complications. Results Median time to surgery was 72 hours. Lack of operating room availability (60.7%) and acute medical problems (33.1%) were the main reasons for delays longer than 48 hours. Overall, rates of hospital death and complications were 4.35% and 45.9%, respectively, but were 13.7% and 74.2% in clinically unstable patients. Longer delays were associated with higher mortality rates and rates of medical complications. After adjustment for age, dementia, chronic comorbid conditions, and functionality, this association did not persist for delays of 120 hours or less but did persist for delays longer than 120 hours (P = 0.002 for overall time effect on death and 0.002 for complications). The risks were attenuated after adjustment for the presence of acute medical conditions as the cause of the delay (P = 0.06 for time effect on mortality and 0.31 on medical complications). Risk for urinary tract infection remained elevated (odds ratio, 1.54 [95% CI, 0.99 to 2.44]). No interaction between delay and age, dementia, or functional status was found. Limitation This was a single-center study without postdischarge follow-up. Conclusion The reported association between late surgery and higher morbidity and mortality in patients with hip fracture is mostly explained by medical reasons for surgical delay, although some association between very delayed surgery and worse outcomes persists. Primary funding source None.

High-throughput VDJ sequencing for quantification of minimal residual disease in chronic lymphocytic leukemia and immune reconstitution assessment

Abstract: The primary cause of poor outcome following allogeneic hematopoietic cell transplantation (HCT) for chronic lymphocytic leukemia (CLL) is disease recurrence. Detection of increasing minimal residual disease (MRD) following HCT may permit early intervention to prevent clinical relapse; however, MRD quantification remains an uncommon diagnostic test because of logistical and financial barriers to widespread use. Here we describe a method for quantifying CLL MRD using widely available consensus primers for amplification of all Ig heavy chain (IGH) genes in a mixture of peripheral blood mononuclear cells, followed by high-throughput sequencing (HTS) for disease-specific IGH sequence quantification. To achieve accurate MRD quantification, we developed a systematic bioinformatic methodology to aggregate cancer clone sequence variants arising from systematic and random artifacts occurring during IGH-HTS. We then compared the sensitivity of IGH-HTS, flow cytometry, and allele-specific oligonucleotide PCR for MRD quantification in 28 samples collected from 6 CLL patients following allogeneic HCT. Using amplimer libraries generated with consensus primers from patient blood samples, we demonstrate the sensitivity of IGH-HTS with 454 pyrosequencing to be 10(-5), with a high correlation between quantification by allele-specific oligonucleotide PCR and IGH-HTS (r = 0.85). From the same dataset used to quantify MRD, IGH-HTS also allowed us to profile IGH repertoire reconstitution after HCT-information not provided by the other MRD methods. IGH-HTS using consensus primers will broaden the availability of MRD quantification in CLL and other B cell malignancies, and this approach has potential for quantitative evaluation of immune diversification following transplant and nontransplant therapies.

A 2010 working formulation for the standardization of definitions of infections in cardiothoracic transplant recipients.

Abstract: Shahid Husain, MD, MS, Martha L. Mooney, MD, MS, FACP, Lara Danziger-Isakov, MD, MPH, Frauke Mattner, MD, PhD, Nina Singh, MD, Robin Avery, MD, FIDSA, Michael Ison, MD, MS, Atul Humar, MD, MSc, Robert F. Padera, MD, PhD, Leo P. Lawler, MD, FRCR, Andy Fisher, PhD, FRCP, Richard J. Drew, MD, Kate F. Gould, MBBS, MRCP, FRCP, Amparo Sole, MD, PhD, Sean Studer, MD, MSc, Patricia Munoz, MD, Lianne G. Singer, MD, FRCPC, and Margaret Hannan, MD, FRCP, FRCPath, for the ISHLT Infectious Diseases Council Working Group on Definitions From the Division of Infectious Diseases, Transplant Infectious Diseases, University Health Network, University of Toronto, Toronto, Ontario, Canada; Eastern Virginia Medical School, Sentara Norfolk Transplant Center, Norfolk, Virginia; Center for Pediatric Infectious Diseases, Department of Infectious Disease, Medicine Institute, The Cleveland Clinic, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio; Infection Control and Hospital Epidemiology, Institute for Medical Microbiology, Hannover Medical School, Hannover, Germany; Division of Infectious Diseases, Veteran Affairs Hospital, University of Pittsburgh, Pittsburgh, Pennsylvania; Divisions of Infectious Diseases and Organ Transplantation, Northwestern University, Feinberg School of Medicine, Chicago, Illinois; Department of Medicine, Division of Infectious Diseases, University of Alberta, Edmonton, Alberta, Canada; Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts; Respiratory Transplant Medicine, Newcastle University, Institute of Transplantation, Freeman Hospital, Newcastle Upon Tyne, UK; Mater Misericordiae University Hospital, Dublin, Ireland; Health Protection Agency Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle, UK; Hospital Universitario La Fe, Valencia, Spain; Division of Pulmonary & Critical Care, Newark Beth Israel Medical Center, Newark, New Jersey; and Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Maranon, Universidad Complutense, Madrid, Spain.

Primary angioplasty vs. fibrinolysis in very old patients with acute myocardial infarction: TRIANA (TRatamiento del Infarto Agudo de miocardio eN Ancianos) randomized trial and pooled analysis with previous studies.

Abstract: Aims To compare primary percutaneous coronary intervention (pPCI) and fibrinolysis in very old patients with ST-segment elevation myocardial infarction (STEMI), in whom head-to-head comparisons between both strategies are scarce. Methods and results Patients ≥75 years old with STEMI <6 h were randomized to pPCI or fibrinolysis. The primary endpoint was a composite of all-cause mortality, re-infarction, or disabling stroke at 30 days. The trial was prematurely stopped due to slow recruitment after enroling 266 patients (134 allocated to pPCI and 132 to fibrinolysis). Both groups were well balanced in baseline characteristics. Mean age was 81 years. The primary endpoint was reached in 25 patients in the pPCI group (18.9%) and 34 (25.4%) in the fibrinolysis arm [odds ratio (OR), 0.69; 95% confidence interval (CI) 0.38–1.23; P = 0.21]. Similarly, non-significant reductions were found in death (13.6 vs. 17.2%, P = 0.43), re-infarction (5.3 vs. 8.2%, P = 0.35), or disabling stroke (0.8 vs. 3.0%, P = 0.18). Recurrent ischaemia was less common in pPCI-treated patients (0.8 vs. 9.7%, P < 0.001). No differences were found in major bleeds. A pooled analysis with the two previous reperfusion trials performed in older patients showed an advantage of pPCI over fibrinolysis in reducing death, re-infarction, or stroke at 30 days (OR, 0.64; 95% CI 0.45–0.91). Conclusion Primary PCI seems to be the best reperfusion therapy for STEMI even for the oldest patients. Early contemporary fibrinolytic therapy may be a safe alternative to pPCI in the elderly when this is not available. Clinicaltrials.gov # [NCT00257309][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00257309&atom=%2Fehj%2Fearly%2F2010%2F10%2F21%2Feurheartj.ehq375.atom

Short-term, light- to moderate-intensity exercise training improves leg muscle strength in the oldest old: a randomized controlled trial.

Abstract: OBJECTIVES: To assess the effects of an 8-week exercise training program with a special focus on light- to moderate-intensity resistance exercises (30�70% of one repetition maximum, 1RM) and a subsequent 4-week training cessation period (detraining) on muscle strength and functional capacity in participants aged 90 and older. DESIGN: Randomized controlled trial performed during March to September 2009. SETTING: Geriatric nursing home. PARTICIPANTS: Forty nonagenarians (90�97) were randomly assigned to an intervention or control group (16 women and 4 men per group). INTERVENTION: Eight-week muscle strength exercise intervention focused on lower limb strength exercises of light to moderate intensity. MEASUREMENTS: Primary outcome: 1RM leg press. Secondary outcomes: handgrip strength, 8-m walk test, 4-step stairs test, Timed Up and Go test, and number of falls. RESULTS: A significant group by time interaction effect (P=.02) was observed only for the 1RM leg press. In the intervention group, 1RM leg press increased significantly with training by 10.6 kg [95% confidence interval (CI)=4.1�17.1 kg; P=.01]. Except for the mean group number of falls, which were 1.2 falls fewer per participant in the intervention group (95% CI=0.0�3.0; P=.03), no significant training effect on the secondary outcome measures was found.

Oral desensitization as a useful treatment in 2‐year‐old children with cow's milk allergy

Abstract: Summary Background Limited published evidence shows oral desensitization to be a potential intervention option for cow's milk protein (CMPs) allergy. Objective The aim of this study was to evaluate the safety and efficacy of oral desensitization in 2-year-old children with cow's milk allergy, as a treatment alternative to elimination diet. Methods A total of 60 children aged 24–36 months with IgE-mediated allergy to CMPs were included in this multi-center study and were randomized into two groups. Thirty children (group A: treatment group) began oral desensitization immediately, whereas the remaining 30 (group B: control group) were kept on a milk-free diet and followed-up for 1 year. Results After 1-year follow-up period, 90% of the children in group A had become completely tolerant vs. 23% of the children in group B. In group A, cow's milk skin reactivity and serum-specific IgE to milk and casein decreased significantly from the initial assessment, whereas group B showed no significant change after 1 year of follow-up. Twenty-four patients (80%) developed some reaction during the treatment period: 14 children developed moderate reaction (47%) and 10 mild reaction (33%). The most common manifestations were urticaria-angioedema, followed by cough. Conclusions and Clinical Relevance In this study, oral desensitization was found to be effective in a significant percentage of 2-year-old children with cow's milk allergy. Oral desensitization appears to be efficacious as an alternative to elimination diet in the treatment of 2-year-old children with cow's milk allergy. The side-effect profile appears acceptable but requires further study. Cite this as: A. Martorell, B. De la Hoz, M. D. Ibanez, J. Bone, M. S. Terrados, A. Michavila, A. M. Plaza, E. Alonso, J. Garde, S. Nevot, L. Echeverria, C. Santana, J. C. Cerda, C. Escudero, I. Guallar, M. Piquer, L. Zapatero, L. Ferre, T. Bracamonte, A. Muriel, M. I. Martinez and R. Felix, Clinical & Experimental Allergy, 2011 (41) 1297–1304.

Decoding Temporal Structure in Music and Speech Relies on Shared Brain Resources but Elicits Different Fine-Scale Spatial Patterns

Abstract: Music and speech are complex sound streams with hierarchical rules of temporal organization that become elaborated over time. Here, we use functional magnetic resonance imaging to measure brain activity patterns in 20 right-handed nonmusicians as they listened to natural and temporally reordered musical and speech stimuli matched for familiarity, emotion, and valence. Heart rate variability and mean respiration rates were simultaneously measured and were found not to differ between musical and speech stimuli. Although the same manipulation of temporal structure elicited brain activation level differences of similar magnitude for both music and speech stimuli, multivariate classification analysis revealed distinct spatial patterns of brain responses in the 2 domains. Distributed neuronal populations that included the inferior frontal cortex, the posterior and anterior superior and middle temporal gyri, and the auditory brainstem classified temporal structure manipulations in music and speech with significant levels of accuracy. While agreeing with previous findings that music and speech processing share neural substrates, this work shows that temporal structure in the 2 domains is encoded differently, highlighting a fundamental dissimilarity in how the same neural resources are deployed.

Methicillin-Susceptible Staphylococcus aureus Endocarditis Isolates Are Associated With Clonal Complex 30 Genotype and a Distinct Repertoire of Enterotoxins and Adhesins

Abstract: Staphylococcus aureus is the most common cause of both infective endocarditis (IE) [1] and soft tissue infection (STI) [2] in the industrialized world. The frequency of S. aureus as a human pathogen is thought to be due in part to its diverse armamentarium of virulence-associated genes. Although substantial evidence suggests that clinical manifestations of S. aureus are influenced by the genetic characteristics of the infecting strain [3–7], the association between S. aureus genes and severity of illness is incompletely understood. Previously, we demonstrated a significant association between specific S. aureus isolates genotypes and infection severity [4]. We used multilocus sequence typing (MLST) to show that clonal complex (CC) 5 and CC30 were significantly associated with the presence of IE and bone and joint infection among 371 clinically well-characterized S. aureus isolates from a single geographical region. However, these findings must be confirmed prior to being considered broadly generalizable. The current investigation seeks to externally validate these previously observed associations between bacterial genotype and infection severity in S. aureus. To do this, we used bacterial isolates from 2 large multinational cohorts of patients with distinct forms of staphylococcal disease: IE and STI.

Plerixafor plus granulocyte CSF can mobilize hematopoietic stem cells from multiple myeloma and lymphoma patients failing previous mobilization attempts: EU compassionate use data.

Abstract: Plerixafor was recently approved by the US Food and Drug Administration (FDA) and the European Medicines Evaluation Agency (EMEA) to enhance stem cell mobilization for autologous transplant in patients with lymphoma and multiple myeloma. In this study, we present the first European compassionate use experience in mobilization failures, patients who are hardest to remobilize but were not included in registration trials. A total of 56 consecutive patients from 15 centers in Spain and the United Kingdom were included: age 60 (33-69) years; 29 men (32 with myeloma and 24 with lymphoma); 2 lines of previous chemotherapy (1-10); 73 previously failed mobilization attempts with G-CSF (28), chemotherapy plus G-CSF (43) or G-CSF plus SCF(2). Overall, 71% of patients reached >= 10 CD34+ cells per mu L with plerixafor on day 5 after a 7.6-fold expansion from day 4. A total of 42 patients (75%) collected >= 2 x 10(6), average 3.0 +/- 1.7 (0.4-10.6) CD34+ cells per kg with plerixafor plus G-CSF. There were no severe drug-related adverse events. In all, 35 patients (63%) underwent transplant, receiving an average of 3.1 +/- 1.2 (1.9-7.7) x 10(6) CD34+ cells per kg. All patients engrafted neutrophils (day 12; 13.4 +/- 0.8; 8-30) and platelets (day 15; 18.5 +/- 2.4; 8-33). In our experience, plerixafor offers an effective alternative to collect sufficient CD34+ cells for autologous SCT from patients who fail conventional mobilization methods, with good tolerance and a high success rate. Bone Marrow Transplantation (2011) 46, 52-58; doi:10.1038/bmt.2010.54; published online 22 March 2010

Elemental Bioimaging in Kidney by LA–ICP–MS As a Tool to Study Nephrotoxicity and Renal Protective Strategies in Cisplatin Therapies

Abstract: A laser ablation inductively coupled plasma mass spectrometry (LA–ICP–MS)-based methodology is presented for Pt, Cu, and Zn bioimaging on whole kidney 3 μm sagittal sections from rats treated with pharmacological doses of cisplatin, which were sacrificed once renal damage had taken place. Pt turned out to accumulate in the kidney cortex and corticomedullary junction, corresponding to areas where the proximal tubule S3 segments (the most sensitive cells to cisplatin nephrotoxicity) are located. This demonstrates the connection between platinum accumulation and renal damage proved by histological examination of HE-stained sections and evaluation of serum and urine biochemical parameters. Cu and Zn distribution maps revealed a significant displacement in cells by Pt, as compared to control tissues. A dramatic decrease in the Pt accumulation in the cortex was observed when cilastatin was coadministered with cisplatin, which can be related to its nephroprotective effect. Excellent imaging reproducibility, sens...

Dendritic Cell-Specific ICAM-3–Grabbing Nonintegrin Expression on M2-Polarized and Tumor-Associated Macrophages Is Macrophage-CSF Dependent and Enhanced by Tumor-Derived IL-6 and IL-10

Abstract: Dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN; CD209) is a human pathogen-attachment C-type lectin with no obvious murine ortholog and for which ligation leads to enhanced anti-inflammatory cytokine release and altered proinflammatory cytokine production. Although induced by IL-4 in monocytes and considered as a DC marker, DC-SIGN expression on human APCs under homeostatic conditions is so far unexplained. We report in this study that M-CSF enhances DC-SIGN expression on in vitro derived anti-inflammatory macrophages and that M-CSF mediates the induction of DC-SIGN by fibroblast- and tumor cell-conditioned media. The M-CSF-inducible DC-SIGN expression along monocyte-to-macrophage differentiation is dependent on JNK and STAT3 activation, potentiated by STAT3-activating cytokines (IL-6, IL-10), and abrogated by the M1-polarizing cytokine GM-CSF. In pathological settings, DC-SIGN expression is detected in tumor tissues and on ex vivo-isolated CD14(+) CD163(+) IL-10-producing tumor-associated macrophages. Importantly, DC-SIGN Abs reduced the release of IL-10 from macrophages exposed to Lewis(x)-expressing SKBR3 tumor cells. These results indicate that DC-SIGN is expressed on both wound-healing (IL-4-dependent) and regulatory (M-CSF-dependent) alternative (M2) macrophages and that DC-SIGN expression on tumor-associated macrophages might help tumor progression by contributing to the maintenance of an immunosuppressive environment.

Prevalence of geriatric syndromes and impact on clinical and functional outcomes in older patients with acute cardiac diseases

Abstract: Objective To assess the prevalence of major geriatric syndromes (MGSs)―frailty, cognitive impairment, severe dependence and depression―and their influence on outcomes in unselected patients with acute cardiac diseases. Design Observational prospective study with 12-month clinical and functional follow-up. Setting Clinical cardiology unit of a university hospital in Madrid, Spain. Patients Consecutive patients ≥75 years old urgently admitted to the cardiology unit. Intervention Systematic comprehensive geriatric assessment. Main outcome measures 12-month rates of mortality, readmission, functional decline and need for new social help. Results Among the 211 patients studied, 127 (60.2%) presented at least one MGS on admission: 86 frailty (40.8%), 67 cognitive impairment (31.8%), 31 severe dependency (14.7%) and 9 depression (4.3%). Patients with MGSs were slightly older (82±5 vs 81±4 years, p=0.02) but did not show greater disease severity or comorbidity. The presence of MGSs was associated with a higher incidence of functional decline during hospitalisation (35.7% vs 8.6%, p=0.002) and higher 12-month age-, comorbidity- and diagnosis-adjusted risks of readmission (OR, 2.1.92; 95% CI 0.98 to 3.7), functional decline (OR, 2.86; 95% CI 1.41 to 5.79) and need for new social help (OR, 3.10; 95% CI 1.45 to 6.60). MGSs were also associated with a higher 12-month mortality rate, which was only obvious in patients hospitalised for heart failure but not for other reasons. Conclusions A majority of older patients hospitalised for acute cardiac conditions in a cardiology department show at least one MGS on admission. MGSs are associated with poorer inhospital and postdischarge functional and clinical outcomes, particularly in patients with heart failure.

Cannabis and First-Episode Psychosis: Different Long-term Outcomes Depending on Continued or Discontinued Use

Abstract: Objective: To examine the influence of cannabis use on long-term outcome in patients with a first psychotic episode, comparing patients who have never used cannabis with (a) those who used cannabis before the first episode but stopped using it during follow-up and (b) those who used cannabis both before the first episode and during follow-up Methods: Patients were studied following their first admission for psychosis They were interviewed at years 1, 3, and 5 At follow-up after 8 years, functional outcome and alcohol and drug abuse were recorded Patients were classified according to cannabis use: 25 had cannabis use before their first psychotic episode and continuous use during follow-up (CU), 27 had cannabis use before their first episode but stopped its use during follow-up (CUS), and 40 never used cannabis (NU) Results: The 3 groups did not differ significantly in symptoms or functional outcome at baseline or during short-term follow-up The CUS group exhibited better long-term functional outcome compared with the other 2 groups and had fewer negative symptoms than the CU group, after adjusting for potential confounders For the CUS group, the effect size was 126 (95% confidence interval [CI] = 065 to 186) for functional outcome and −072 (95% CI = −127 to −014) for negative symptoms All patients experienced improvements in positive symptoms during long-term follow-up Conclusion: Cannabis has a deleterious effect, but stopping use after the first psychotic episode contributes to a clear improvement in outcome The positive effects of stopping cannabis use can be seen more clearly in the long term

Reduced antioxidant defense in early onset first-episode psychosis: a case-control study

Abstract: Our objective is to determine the activity of the antioxidant defense system at admission in patients with early onset first psychotic episodes compared with a control group. Total antioxidant status (TAS) and lipid peroxidation (LOOH) were determined in plasma. Enzyme activities and total glutathione levels were determined in erythrocytes in 102 children and adolescents with a first psychotic episode and 98 healthy controls. A decrease in antioxidant defense was found in patients, measured as decreased TAS and glutathione levels. Lipid damage (LOOH) and glutathione peroxidase activity was higher in patients than controls. Our study shows a decrease in the antioxidant defense system in early onset first episode psychotic patients. Glutathione deficit seems to be implicated in psychosis, and may be an important indirect biomarker of oxidative stress in early-onset schizophrenia. Oxidative damage is present in these patients, and may contribute to its pathophysiology.

Trait and State Attributes of Insight in First Episodes of Early-Onset Schizophrenia and Other Psychoses: A 2-Year Longitudinal Study

Abstract: Background: Increasing evidence supports the important role of illness state and individual characteristics in insight. Methods: Insight, as measured with the Scale to Assess Unawareness of Mental Disorder, over the first 2 years of early-onset first-episode psychosis and its correlations with clinical, socio-demographic, cognitive, and structural brain variables are studied. Results: (1) insight at 2 years is poorer in schizophrenia spectrum disorders (SSDs) than in subjects with other psychoses; (2) the more severe the psychosis, the worse the insight. In SSD, depressive symptoms, poorer baseline executive functioning, lower IQ, longer duration of untreated psychosis (DUP), and poorer premorbid infancy adjustment are associated with poorer insight; frontal and parietal gray matter (GM) reductions at baseline correlate with worse insight into having psychotic symptoms at 2 years; (3) insight into having a mental disorder (Scale to Assess Unawareness of Mental Disorder [SUMD]1) at 1 year, DUP, and baseline IQ are the most consistent variables explaining different aspects of insight at 2 years in SSD patients. IQ and SUMD1 at 1 year, together with left frontal and parietal GM volumes, explain 80% of the variance of insight into having specific psychotic symptoms in SSD patients (adjusted R2 = 0.795, F = 15.576, P < .001). Conclusion: Insight is a complex phenomenon that depends both on severity of psychopathology and also on disease and subject characteristics, such as past adjustment, IQ, DUP, cognitive functioning, frontal and parietal GM volumes, and age, gender, and ethnicity.

Adalimumab induction and maintenance therapy for patients with ulcerative colitis previously treated with infliximab.

Abstract: Aliment Pharmacol Ther 2011; 33: 340–348 Summary Background The long-term efficacy of adalimumab in patients with ulcerative colitis is not well known. Aim To evaluate the short- and long-term outcomes of adalimumab in ulcerative colitis patients previously treated with infliximab. Methods Patients with active ulcerative colitis were treated with adalimumab after failure of other therapies including infliximab. Short-term clinical response and remission were assessed at weeks 4 and 12. The proportion of patients who continued on adalimumab and the proportion of patients who remained colectomy free were assessed over the long term. Results Clinical response at weeks 4 and 12 was achieved in 16 (53%) and 18 (60%) patients, respectively, and clinical remission was obtained in 3 (10%) and 8 (27%) patients, respectively. After a mean 48 weeks’ follow-up, 15 patients (50%) continued on adalimumab. Six patients (20%) required colectomy. All patients who achieved clinical response at week 12 were colectomy free at long term. Conclusions Adalimumab was well tolerated and induced durable clinical response in many patients with otherwise medically refractory ulcerative colitis. Patients achieving clinical response at week 12 avoided colectomy over the long term.

Prevalencia y caracteristicas de la dislipemia en pacientes en prevencion primaria y secundaria tratados con estatinas en Espana. Estudio DYSIS-Espana

Abstract: Introduction and objectives: Patients at high risk of suffering cardiovascular events require medical treatment to optimize their lipid profile. The present analysis evaluates the lipid profiles among Spanish patients receiving statin therapy in the international DYSIS study. Methods: DYSIS is a multinational cross-sectional study carried out in Canada and Europe (n = 22,063). In Spain, 3710 patients treated with statin therapy for at least 3 months were included. We compared data relating to demographic parameters and cardiovascular risk profile. Results: Complete lipid profiles of 3617 patients were recorded. Regarding the high cardiovascular risk patients with complete lipid profiles (n = 2273), 78.9% had a disorder in at least one of the three main lipid parameters: low-density lipoprotein cholesterol (LDLc), high-density lipoprotein cholesterol (HDLc) and/or triglycerides. LDLc was not within target levels in 61.4% of these high risk patients; HDLc was abnormal in 25.3%, and triglycerides were elevated in 37.8%. Overall, LDLc was outside the target range in 63.1%, and 20.7% (n = 668) of those treated with statins were normal for all parameters. Conclusions: Most patients in this study who received statin therapy, particularly those at high cardiovascular risk, were not at the normal lipid parameter levels according to cardiovascular guidelines. Although it is necessary to wait for the final results of current studies on the use of combined lipidmodifying treatments, the management of lipid levels in Spain still has potential for improvement.

La cohorte de la red española de investigación en sida y su biobanco: organización, principales resultados y pérdidas al seguimiento

Abstract: Resumen Introduccion Este articulo describe el desarrollo de la cohorte de la Red Espanola de Investigacion en sida (CoRIS), sus aspectos metodologicos y organizativos, las caracteristicas demograficas y clinicas de los sujetos incluidos y cuantifica las perdidas al seguimiento y sus factores asociados. Metodos Cohorte multicentrica de sujetos naive VIH-positivos reclutados en 28 centros espanoles desde 2004. Se realizaron controles de calidad internos para evaluar inconsistencias o falta de informacion, y las bases de datos se auditaron externamente. Se utilizaron modelos de regresion logistica multivariada. Resultados Hasta octubre de 2009, se incluyeron 5.514 personas, 11.708 personas-ano, con una mediana de seguimiento de 1,81 anos. La mayoria son hombres (78,8%), infectados por transmision sexual (46,1% hombres que tienen sexo con hombres y el 35,2% heterosexuales) y espanoles (69,7%). Durante el seguimiento el 64,5% habian iniciado terapia antirretroviral (ART) y se han producido 201 muertes. El 80,7% eran nuevos diagnosticos de VIH. El 52% tenian al menos una muestra basal en el BioBanco siendo naive a ART. Las perdidas al seguimiento (18,9%) fueron mas frecuentes en jovenes, usuarios de drogas inyectadas, no espanoles, personas sin estudios o primarios, y en los reclutados con un nivel de cd4 superior a 350 cel/mm3. Conclusiones La implementacion de CoRIS ha sido exitosa, con una amplia representacion a nivel estatal, esta reclutando activamente nuevos pacientes con muestras de sangre y tiene una excelente calidad en los datos. Las perdidas al seguimiento son de magnitud similar a otras cohortes, asi como los factores asociados con ellas.