Showing papers by "Hospital General Universitario Gregorio Marañón published in 2010"

Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data

Abstract: Summary Background Locally advanced rectal cancer is usually treated with preoperative chemoradiation. After chemoradiation and surgery, 15–27% of the patients have no residual viable tumour at pathological examination, a pathological complete response (pCR). This study established whether patients with pCR have better long-term outcome than do those without pCR. Methods In PubMed, Medline, and Embase we identified 27 articles, based on 17 different datasets, for long-term outcome of patients with and without pCR. 14 investigators agreed to provide individual patient data. All patients underwent chemoradiation and total mesorectal excision. Primary outcome was 5-year disease-free survival. Kaplan-Meier survival functions were computed and hazard ratios (HRs) calculated, with the Cox proportional hazards model. Subgroup analyses were done to test for effect modification by other predicting factors. Interstudy heterogeneity was assessed for disease-free survival and overall survival with forest plots and the Q test. Findings 484 of 3105 included patients had a pCR. Median follow-up for all patients was 48 months (range 0–277). 5-year crude disease-free survival was 83·3% (95% CI 78·8–87·0) for patients with pCR (61/419 patients had disease recurrence) and 65·6% (63·6–68·0) for those without pCR (747/2263; HR 0·44, 95% CI 0·34–0·57; p Q test and forest plots did not suggest significant interstudy variation. The adjusted HR for pCR for failure was 0·54 (95% CI 0·40–0·73), indicating that patients with pCR had a significantly increased probability of disease-free survival. The adjusted HR for disease-free survival for administration of adjuvant chemotherapy was 0·91 (95% CI 0·73–1·12). The effect of pCR on disease-free survival was not modified by other prognostic factors. Interpretation Patients with pCR after chemoradiation have better long-term outcome than do those without pCR. pCR might be indicative of a prognostically favourable biological tumour profile with less propensity for local or distant recurrence and improved survival. Funding None.

Effect of Allopurinol in Chronic Kidney Disease Progression and Cardiovascular Risk

Abstract: Background and objectives: Hyperuricemia is associated with hypertension, inflammation, renal disease progression, and cardiovascular disease. However, no data are available regarding the effect of allopurinol in patients with chronic kidney disease. Design, setting, participants, & measurements: We conducted a prospective, randomized trial of 113 patients with estimated GFR (eGFR) n = 57) or to continue the usual therapy ( n = 56). Clinical, biochemical, and inflammatory parameters were measured at baseline and at 6, 12, and 24 months of treatment. The objectives of study were: ( 1 ) renal disease progression; ( 2 ) cardiovascular events; and ( 3 ) hospitalizations of any causes. Results: Serum uric acid and C-reactive protein levels were significantly decreased in subjects treated with allopurinol. In the control group, eGFR decreased 3.3 ± 1.2 ml/min per 1.73 m 2 , and in the allopurinol group, eGFR increased 1.3 ± 1.3 ml/min per 1.73 m 2 after 24 months. Allopurinol treatment slowed down renal disease progression independently of age, gender, diabetes, C-reactive protein, albuminuria, and renin-angiotensin system blockers use. After a mean follow-up time of 23.4 ± 7.8 months, 22 patients suffered a cardiovascular event. Diabetes mellitus, previous coronary heart disease, and C-reactive protein levels increased cardiovascular risk. Allopurinol treatment reduces risk of cardiovascular events in 71% compared with standard therapy. Conclusions: Allopurinol decreases C-reactive protein and slows down the progression of renal disease in patients with chronic kidney disease. In addition, allopurinol reduces cardiovascular and hospitalization risk in these subjects.

Trends in length of stay and short-term outcomes among Medicare patients hospitalized for heart failure, 1993-2006.

Abstract: Context Whether decreases in the length of stay during the past decade for patients with heart failure (HF) may be associated with changes in outcomes is unknown. Objective To describe the temporal changes in length of stay, discharge disposition, and short-term outcomes among older patients hospitalized for HF. Design, Setting, and Participants An observational study of 6 955 461 Medicare fee-for-service hospitalizations for HF between 1993 and 2006, with a 30-day follow-up. Main Outcome Measures Length of hospital stay, in-patient and 30-day mortality, and 30-day readmission rates. Results Between 1993 and 2006, mean length of stay decreased from 8.81 days (95% confidence interval [CI], 8.79-8.83 days) to 6.33 days (95% CI, 6.32-6.34 days). In-hospital mortality decreased from 8.5% (95% CI, 8.4%-8.6%) in 1993 to 4.3% (95% CI, 4.2%-4.4%) in 2006, whereas 30-day mortality decreased from 12.8% (95% CI, 12.8%-12.9%) to 10.7% (95% CI, 10.7%-10.8%). Discharges to home or under home care service decreased from 74.0% to 66.9% and discharges to skilled nursing facilities increased from 13.0% to 19.9%. Thirty-day readmission rates increased from 17.2% (95% CI, 17.1%-17.3%) to 20.1% (95% CI, 20.0%-20.2%; all P Conclusion For patients admitted with HF during the past 14 years, reductions in length of stay and in-hospital mortality, less marked reductions in 30-day mortality, and changes in discharge disposition accompanied by increases in 30-day readmission rates were observed.

Community-Onset Bacteremia Due to Extended-Spectrum β-Lactamase-Producing Escherichia coli: Risk Factors and Prognosis

Abstract: Background There is little clinical information about community-onset bloodstream infections (COBSIs) caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (ESBLEC). We investigated the prevalence and risk factors for COBSI due to ESBLEC, and described their clinical features and the impact of COBSI caused by ESBLEC on 14-day mortality. Methods Risk factors were assessed using a multicenter case-control-control study. Influence of ESBL production on mortality was studied in all patients with COBSI due to E. coli. Isolates and ESBLs were microbiologically characterized. Statistical analysis was performed using multivariate logistic regression. Thirteen tertiary care Spanish hospitals participated in the study. Results We included 95 case patients with COBSI due to ESBLEC, which accounted for 7.3% of all COBSI due to E. coli. The ESBL in 83 of these (87%) belonged to the CTX-M family of ESBL, and most were clonally unrelated. Comparison with both control groups disclosed association with health care (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.2-3.8), urinary catheter use (OR, 3.1; 95% CI, 1.5-6.5), and previous antimicrobial use (OR, 2.7; 95% CI, 1.5-4.9) as independent risk factors for COBSI due to ESBLEC. Mortality among patients with COBSI due to ESBLEC was lower among patients who received empirical therapy with beta-lactam/beta-lactam inhibitor combinations or carbapenems (8%-12%) than among those receiving cephalosporins or fluoroquinolones (24% and 29%, respectively). Mortality among patients with COBSI due to E. coli was associated with inappropriate empirical therapy irrespective of ESBL production. Conclusions ESBLEC is an important cause of COBSI due to E. coli. Clinicians should consider adequate empirical therapy with coverage of these pathogens for patients with risk factors.

Substrate and Trigger Ablation for Reduction of Atrial Fibrillation (STAR AF): a randomized, multicentre, international trial

Abstract: Aims This multicentre, randomized trial compared three strategies of AF ablation: ablation of complex fractionated electrograms (CFE) alone, pulmonary vein isolation (PVI) alone, and combined PVI + CFE ablation, using standardized automated mapping software. Methods and results Patients with drug-refractory, high-burden paroxysmal (episodes >6 h, >4 in 6 months) or persistent atrial fibrillation (AF) were enrolled at eight centres. Patients ( n = 100) were randomized to one of three arms. For CFE alone ( n = 34), spontaneous/induced AF was mapped using validated, automated CFE software and all sites 30 s at 1 year. Patients (age 57 ± 10 years, LA size 42 ± 6 mm) were 35% persistent AF. In CFE, ablation terminated AF in 68%. Only 0.4 PVs per patient were isolated as a result of CFE. In PVI, 94% had all four PVs successfully isolated. In PVI + CFE, 94% had all four PVs isolated, 76% had inducible AF with additional CFE ablation, with 73% termination of AF. There were significantly more repeat procedures in the CFE arm (47%) vs. PVI (31%) or PVI + CFE (15%) ( P = 0.01). After one procedure, PVI + CFE had a significantly higher freedom from AF (74%) compared with PVI (48%) and CFE (29%) ( P = 0.004). After two procedures, PVI + CFE still had the highest success (88%) compared with PVI (68%) and CFE (38%) ( P = 0.001). Ninety-six percent of these patients were off anti-arrhythmics. Complications were two tamponades, no PV stenosis, and no mortality. Conclusion In high-burden paroxysmal/persistent AF, PVI + CFE has the highest freedom from AF vs. PVI or CFE alone after one or two procedures. Complex fractionated electrogram alone has the lowest one and two procedure success rates with a higher incidence of repeat procedures. ClinicalTrials.gov identifier number NCT00367757.

Catheter Ablation of Recurrent Scar‐Related Ventricular Tachycardia Using Electroanatomical Mapping and Irrigated Ablation Technology: Results of the Prospective Multicenter Euro‐VT‐Study

Abstract: Ventricular tachycardia (VT) late after myocardial infarction is an important contributor to morbidity and mortality. This prospective multicenter study assessed the efficacy and safety of electroanatomical mapping in combination with open-saline irrigated ablation technology for ablation of chronic recurrent mappable and unmappable VT in remote myocardial infarction.

Wild-Type MIC Distributions and Epidemiological Cutoff Values for the Triazoles and Six Aspergillus spp. for the CLSI Broth Microdilution Method (M38-A2 Document)

Abstract: Clinical breakpoints have not been established for mold testing. Wild-type (WT) MIC distributions (organisms in a species/drug combination with no detectable acquired resistance mechanisms) were defined in order to establish epidemiologic cutoff values (ECVs) for five Aspergillus spp. and itraconazole, posaconazole, and voriconazole. Also, we have expanded prior ECV data for Aspergillus fumigatus. The number of available isolates varied according to the species/triazole combination as follows: 1,684 to 2,815 for A. fumigatus, 323 to 592 for A. flavus, 131 to 143 for A. nidulans, 366 to 520 for A. niger, 330 to 462 for A. terreus, and 45 to 84 for A. versicolor. CLSI broth microdilution MIC data gathered in five independent laboratories in Europe and the United States were aggregated for the analyses. ECVs expressed in μg/ml were as follows (percentages of isolates for which MICs were equal to or less than the ECV are in parentheses): A. fumigatus, itraconazole, 1 (98.8%); posaconazole, 0.5 (99.2%); voriconazole, 1 (97.7%); A. flavus, itraconazole, 1 (99.6%); posaconazole, 0.25 (95%); voriconazole, 1 (98.1%); A. nidulans, itraconazole, 1 (95%); posaconazole, 1 (97.7%); voriconazole, 2 (99.3%); A. niger, itraconazole, 2 (100%); posaconazole, 0.5 (96.9%); voriconazole, 2 (99.4%); A. terreus, itraconazole, 1 (100%); posaconazole, 0.5 (99.7%); voriconazole, 1 (99.1%); A. versicolor, itraconazole, 2 (100%); posaconazole, 1 (not applicable); voriconazole, 2 (97.5%). Although ECVs do not predict therapy outcome as clinical breakpoints do, they may aid in detection of azole resistance (non-WT MIC) due to cyp51A mutations, a resistance mechanism in some Aspergillus spp. These ECVs should be considered for inclusion in the future CLSI M38-A2 document revision.

Adjuvant Docetaxel for High-Risk, Node-Negative Breast Cancer

Abstract: BACKGROUND A regimen of docetaxel, doxorubicin, and cyclophosphamide (TAC) is superior to a regimen of fluorouracil, doxorubicin, and cyclophosphamide (FAC) when used as adjuvant therapy in women with node-positive breast cancer. The value of taxanes in the treatment of node-negative disease has not been determined. METHODS We randomly assigned 1060 women with axillary-node-negative breast cancer and at least one high-risk factor for recurrence (according to the 1998 St. Gallen criteria) to treatment with TAC or FAC every 3 weeks for six cycles after surgery. The primary end point was disease-free survival after at least 5 years of follow-up. Secondary end points included overall survival and toxicity. RESULTS At a median follow-up of 77 months, the proportion of patients alive and disease-free was higher among the 539 women in the TAC group (87.8%) than among the 521 women in the FAC group (81.8%), representing a 32% reduction in the risk of recurrence with TAC (hazard ratio, 0.68; 95% confidence interval [CI], 0.49 to 0.93; P=0.01 by the log-rank test). This benefit was consistent, regardless of hormone-receptor status, menopausal status, or number of high-risk factors. The difference in survival rates (TAC, 95.2%; FAC, 93.5%) was not significant (hazard ratio, 0.76; 95% CI, 0.45 to 1.26); however, the number of events was small (TAC, 26; FAC, 34). Rates of grade 3 or 4 adverse events were 28.2% with TAC and 17.0% with FAC (P<0.001). Toxicity associated with TAC was diminished when primary prophylaxis with granulocyte colony-stimulating factor was provided. CONCLUSIONS As compared with adjuvant FAC, adjuvant TAC improved the rate of disease-free survival among women with high-risk, node-negative breast cancer. (Funded by GEICAM and Sanofi-Aventis; ClinicalTrials.gov number, NCT00121992.).

Early routine percutaneous coronary intervention after fibrinolysis vs. standard therapy in ST-segment elevation myocardial infarction: a meta-analysis

Abstract: Aims Multiple trials in patients with ST-segment elevation myocardial infarction (STEMI) compared early routine percutaneous coronary intervention (PCI) after successful fibrinolysis vs. standard therapy limiting PCI only to patients without evidence of reperfusion (rescue PCI). These trials suggest that all patients receiving fibrinolysis should receive mechanical revascularization within 24 h from initial hospitalization. However, individual trials could not demonstrate a significant reduction in ‘hard’ endpoints such as death and reinfarction. We performed a meta-analysis of randomized controlled trials to define the benefits of early PCI after fibrinolysis over standard therapy on clinical and safety endpoints in STEMI. Methods and results We identified seven eligible trials, enrolling a total of 2961 patients. No difference was found in the incidence of death at 30 days between the two strategies. Early PCI after successful fibrinolysis reduced the rate of reinfarction (OR: 0.55, 95% CI: 0.36–0.82; P = 0.003), the combined endpoint death/reinfarction (OR: 0.65, 95% CI: 0.49–0.88; P = 0.004) and recurrent ischaemia (OR: 0.25, 95% CI: 0.13–0.49; P < 0.001) at 30-day follow-up. These advantages were achieved without a significant increase in major bleeding (OR: 0.93, 96% CI: 0.67–1.34; P = 0.70) or stroke (OR: 0.63, 95% CI: 0.31–1.26; P = 0.21). The benefits of a routine invasive strategy over standard therapy were maintained at 6–12 months, with persistent significant reduction in the endpoints reinfarction (OR: 0.64, 95% CI: 0.40–0.98; P = 0.01) and combined death/reinfarction (OR: 0.71, 95% CI: 0.52–0.97; P = 0.03). Conclusion Early routine PCI after fibrinolysis in STEMI patients significantly reduced reinfarction and recurrent ischaemia at 1month, with no significant increase in adverse bleeding events compared to standard therapy. Benefits of early PCI persist at 6–12 month follow-up.

Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome.

Abstract: Several syndromes manifest as recurrent daily fevers, skin lesions, and multisystem inflammation. We describe 4 patients with early-onset recurrent fevers, annular violaceous plaques, persistent violaceous eyelid swelling, low weight and height, lipodystrophy, hepatomegaly, and a range of visceral inflammatory manifestations. Laboratory abnormalities included chronic anemia, elevated acute-phase reactants, and raised liver enzymes. Histopathologic examination of lesional skin showed atypical mononuclear infiltrates of myeloid lineage and mature neutrophils. Our patients have a distinctive early-onset, chronic inflammatory condition with atypical or immature myeloid infiltrates in the skin. We propose the acronym CANDLE (chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature) syndrome for this newly described disorder, which is probably genetic in origin.

Accuracy and clinical relevance of computed tomography scan interpretation of peritoneal cancer index in colorectal cancer peritoneal carcinomatosis: A multi‐institutional study

Abstract: Background Evaluation of peritoneal metastases by computed tomography (CT) scans is challenging and has been reported to be inaccurate. Methods A multi-institutional prospective observational registry study of patients with peritoneal carcinomatosis from colorectal cancer was conducted and a subset analysis was performed to examine peritoneal cancer index (PCI) based on CT and intraoperative exploration. Results Fifty-two patients (mean age 52.6 ± 12.4 years) from 16 institutions were included in this study. Inaccuracies of CT-based assessment of lesion sizes were observed in the RUQ (P = 0.004), LLQ (P < 0.0005), RLQ (P = 0.003), distal jejunum (P = 0.004), and distal ileum (P < 0.0005). When CT-PCI was classified based on the extent of carcinomatosis, 17 cases (33%) were underestimations, of which, 11 cases (21%) were upstaged from low to moderate, 4 cases (8%) were upstaged from low to severe, and 2 cases (4%) were upstaged from moderate to severe. Relevant clinical discordance where an upstage occurred to severe carcinomatosis constituted a true inaccuracy and was observed in six cases (12%). Conclusions The actual clinical impact of inaccuracies of CT-PCI was modest. CT-PCI will remain as a mandatory imaging tool and may be supplemented with other tools including positron emission tomography scan or diagnostic laparoscopy, in the patient selection for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. J. Surg. Oncol. 2010;102:565–570. © 2010 Wiley-Liss, Inc.

Efficacy and safety of various repeat treatment dosing regimens of rituximab in patients with active rheumatoid arthritis: results of a Phase III randomized study (MIRROR)

Abstract: Objective. To evaluate the efficacy and safety of three dosing and repeat treatment regimens of rituximab (RTX) plus MTX in patients with active RA. Methods. Patients with active RA despite stable MTX (10–25 mg/week) were randomly assigned to one of the three treatment regimens comprising two courses of RTX given 24 weeks apart: 2 × 500 and 2 × 500 mg; 2 × 500 and 2 × 1000 mg (dose escalation); and 2 × 1000 and 2 × 1000 mg. The primary endpoint was proportion of patients achieving ACR20 at Week 48. Results. At Week 48, ACR20 responses were not statistically significantly different between the dose regimens. Compared with RTX 2 × 500 mg (n = 134) or dose escalation (n = 119), ACR and European League Against Rheumatism (EULAR) outcomes in the RTX 2 × 1000 mg group (n = 93) were consistently higher, with significantly more patients achieving EULAR responses (P = 0.0495). At Week 48, rituximab 2 × 1000 mg was associated with a higher proportion of patients who, following retreatment, maintained or improved their Week 24 responses. Dose escalation from 2 × 500 to 2 × 1000 mg did not appear to be associated with improved outcomes compared with continual 2 × 500 mg. All RTX regimens demonstrated comparable safety. Conclusions. RTX 2 × 500 and 2 × 1000 mg could not be clearly differentiated, although some efficacy outcomes suggest improved outcomes in the rituximab 2 × 1000 mg group. Retreatment from Week 24 resulted in a sustained suppression of disease activity through to Week 48. Trial registration. ClinicalTrials.gov, http://clinicaltrials.gov/, NCT00422383.

Risk Factors and Prognosis of Nosocomial Bloodstream Infections Caused by Extended-Spectrum-β-Lactamase-Producing Escherichia coli

Abstract: Extended-spectrum-β-lactamase (ESBL)-producing Escherichia coli (ESBLEC) is an increasing cause of community and nosocomial infections worldwide. However, there is scarce clinical information about nosocomial bloodstream infections (BSIs) caused by these pathogens. We performed a study to investigate the risk factors for and prognosis of nosocomial BSIs due to ESBLEC in 13 Spanish hospitals. Risk factors were assessed by using a case-control-control study; 96 cases (2 to 16% of all nosocomial BSIs due to E. coli in the participating centers) were included; the most frequent ESBL was CTX-M-14 (48% of the isolates). We found CTX-M-15 in 10% of the isolates, which means that this enzyme is emerging as a cause of invasive infections in Spain. By repetitive extragenic palindromic sequence-PCR, most isolates were found to be clonally unrelated. By multivariate analysis, the risk factors for nosocomial BSIs due to ESBLEC were found to be organ transplant (odds ratio [OR] = 4.8; 95% confidence interval [CI] = 1.4 to 15.7), the previous use of oxyimino-β-lactams (OR = 6.0; 95% CI = 3.0 to 11.8), and unknown BSI source (protective; OR = 0.4; 95% CI = 0.2 to 0.9), and duration of hospital stay (OR = 1.02; 95% CI = 1.00 to 1.03). The variables independently associated with mortality were a Pitt score of >1 (OR = 3.9; 95% CI = 1.2 to 12.9), a high-risk source (OR = 5.5; 95% CI = 1.4 to 21.9), and resistance to more than three antibiotics, apart from penicillins and cephalosporins (OR = 6.5; 95% CI = 1.4 to 30.0). Inappropriate empirical therapy was not associated with mortality. We conclude that ESBLEC is an important cause of nosocomial BSIs. The previous use of oxyimino-β-lactams was the only modifiable risk factor found. Resistance to drugs other than penicillins and cephalosporins was associated with increased mortality.

Changes in vitamin D levels in patients with systemic lupus erythematosus: Effects on fatigue, disease activity, and damage.

Abstract: Objective To analyze whether changes in serum 25-hydroxyvitamin D (25[OH]D) levels affect activity, irreversible organ damage, and fatigue in systemic lupus erythematosus (SLE). Methods We performed an observational study of 80 patients with SLE included in a previous cross-sectional study of 25(OH)D, reassessed 2 years later. Oral vitamin D3 was recommended in those with low baseline 25(OH)D levels. The relationship between changes in 25(OH)D levels from baseline and changes in fatigue (measured by a 0–10 visual analog scale [VAS]), SLE activity (measured by the Systemic Lupus Erythematosus Disease Activity Index [SLEDAI]), and irreversible organ damage (measured by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index [SDI]) were analyzed. Results Sixty patients took vitamin D3. Mean 25(OH)D levels increased among all treated patients (P = 0.044), in those with baseline vitamin D levels <30 ng/ml (P < 0.001), and in those with baseline vitamin D levels <10 ng/ml (P = 0.005). Fifty-seven patients (71%) still had 25(OH)D levels <30 ng/ml and 5 (6%) had 25(OH)D levels <10 ng/ml. Inverse significant correlations between 25(OH)D levels and the VAS (P = 0.001) and between changes in 25(OH)D levels and changes in the VAS in patients with baseline 25(OH)D levels <30 ng/ml (P = 0.017) were found. No significant correlations were seen between the variation of the SLEDAI or SDI values and the variation in 25(OH)D levels (P = 0.87 and P = 0.63, respectively). Conclusion Increasing 25(OH)D levels may have a beneficial effect on fatigue. Our results do not support any effects of increasing 25(OH)D levels on SLE severity, although they are limited by the insufficient 25(OH)D response to the recommended regimen of oral vitamin D3 replacement.

European workshop in periodontal health and cardiovascular disease—scientific evidence on the association between periodontal and cardiovascular diseases: a review of the literature

Abstract: In the last 10 years, a rising number of epidemiological investigations have studied the possible association between chronic oral infections and cardiovascular diseases (CVD). These studies were based on the hypothesis that periodontal diseases (PD), may confer an independent risk for CVD. There is, however, still controversy whether these associations are causal or whether there are common aetiological factors common to both diseases (residual confounding). The objective of this paper was to review the possible association between PD and CVD on both the epidemiological association and the possible preventive and treatment implications.Although the reported epidemiological studies have shown a significant, albeit week associations, we still lack properly designed clinical trials demonstrating that these chronic infections are independent factors of cardiovascular risk. The use of surrogate variables assessing the infective load and measures of subclinical atherosclerosis have clearly shown, not only a significant pathogenic relationship, but also a significant impact after periodontal therapy.From a public health perspective, if further studies consistently identify PD as a risk factor for CHD and treatment studies show benefit, the implications are significant, since PD is mostly avoidable and treatable when not prevented. In addition, good preventive dental care has multiple other benefits, particularly on quality of life. Furthermore, identifying individuals at higher risk for CHD than predicted by traditional risk factors could facilitate treatment of risk factors known to decrease CHD events in high-risk individuals and this might be significant given the high prevalence of PD in the population and the common problem of CHD.

The role of cardiac registries in evidence-based medicine.

Abstract: Cardiovascular disease remains the primary cause of mortality, and a major cause of disability in the developed world.1 This significant burden necessitates ongoing improvements in patient management, to minimize the impact of cardiovascular conditions on both patients and healthcare systems. These improvements in cardiovascular care are promoted by an evidence-based approach, shaped by comprehensive clinical guidelines. The scientific basis of recommendations is an important feature of clinical guidelines, and influences the degree to which they are followed in clinical practice.2 Recent studies have assigned the highest evidence grading to randomized controlled trials (RCTs) that are clinically important, and representative of the clinical population covered by the guideline recommendation.3 For example, this highest grading was assigned to a recommendation based on a meta-analysis of RCTs showing low-dose diuretics to be the most effective first-line treatment for cardiovascular event prevention in hypertensive patients. This study reviewed data from 42 RCTs which were, crucially, representative of the population that the recommendation was made for (i.e. hypertensive patients).3,4 The importance of the applicability of evidence to recommendations highlights the need to consider evidence from clinically relevant situations, not all of which have been assessed by RCTs. This evidence can originate from expert consensus, as well as non-randomized prospective studies. Although generally providing a lower evidence-level than RCTs,3,5 observational studies can make an important contribution to the evidence base when the study outcomes are clinically important, and the populations involved are representative. Indeed, information from several registries was considered in the recent American Heart Association Acute Coronary Care in the Elderly Scientific Statement.6 Non-randomized prospective registries document the treatment and outcomes for consecutive patients in clinical practice. Therefore, data are gained from a ‘real-world’ selection of patients, many of whom would be excluded from RCTs, …

Comparison of transient elastography and liver biopsy for the assessment of liver fibrosis in HIV/hepatitis C virus-coinfected patients and correlation with noninvasive serum markers.

Abstract: Summary. Transient elastography (FibroScan®) is a novel, rapid and noninvasive technique to assess liver fibrosis. Our objective was to compare transient elastography (TE) and other noninvasive serum indexes as alternatives to liver biopsy in HIV/hepatitis C virus (HCV)-coinfected patients. The fibrosis stage (METAVIR Score), TE, the aspartate aminotransferase-to-platelet ratio index, the Forns fibrosis index, FIB-4 and HGM-2 indexes were assessed in 100 patients between January 2007 and January 2008. The diagnostic values were compared by calculating the area under the receiver operating characteristic curves (AUROCs). Using TE, the AUROC (95% CI) of liver stiffness was 0.80 (0.72–0.89) when discriminating between F ≤ 1 and F > 2, 0.93 (0.85–1.00) when discriminating between F ≤ 2 and F > 3 and 0.99 (0.97–1.00) when discriminating between F ≤ 3 and F4. For the diagnosis of F ≥ 3, the AUROCs of TE were significantly higher than those obtained with the other four noninvasive indexes. Based on receiver operating characteristic curves, three cutoff values were chosen to identify F ≤ 1 (<7 kPa), F ≥ 3 (≥11 kPa) and F4 (≥14 kPa). Using these best cutoff scores, the negative predictive value and positive predictive value were 81.1% and 70.2% for the diagnosis of F ≤ 1, 96.3% and 60% for the diagnosis of F ≥ 3 and 100% and 57.1% for the diagnosis of F4. Thus, Transient elastography accurately predicted liver fibrosis and outperformed other simple noninvasive indexes in HIV/HCV-coinfected patients. Our data suggest that TE is a helpful tool for guiding therapeutic decisions in clinical practice.

Neuropsychological functioning in early-onset first-episode psychosis: comparison of diagnostic subgroups

Abstract: The aims of this study were to examine the nature and extent of cognitive impairment in first-episode early-onset psychosis (FE-EOP) soon after their stabilisation and to search for potential differences according to specific diagnostic sub-groups of patients. As part of a Spanish multicentre longitudinal study, 107 FE-EOP patients and 98 healthy controls were assessed on the following cognitive domains: attention, working memory, executive functioning, and verbal learning and memory. Three diagnostic categories were established in the patient sample: schizophrenia (n = 36), bipolar disorder (n = 19), and other psychosis (n = 52). Patients performed significantly worse than controls in all cognitive domains. The three diagnostic sub-groups did not differ in terms of impaired/preserved cognitive functions or degree of impairment. FE-EOP patients show significant cognitive impairment that, during this early phase, seems to be non-specific to differential diagnosis.

Molecular predictors of efficacy of adjuvant weekly paclitaxel in early breast cancer

Abstract: Treatment with fluororacil, epirubicin, and cyclophosphamide followed by weekly paclitaxel (FEC-P) yielded superior disease-free survival than FEC in the adjuvant breast cancer trial GEICAM 9906. We evaluate molecular subtypes predictive of prognosis and paclitaxel response in this trial. Two molecular subtype classifications based on conventional immunohistochemical and fluorescent in situ hybridization determinations were used: #1: Four groups segregated according to the combination of hormone receptor (HR) and HER2 status; #2: Intrinsic subtype classification (Triple Negative (TN), HER2, Luminal B and Luminal A). Results: Both subtype classifications yielded prognostic and predictive information. HR +/HER2− patients (and Luminal A patients) had a significantly better outcome than the other subgroups of patients. The superiority of FEC-P over FEC was clearly more marked in HR−/HER2− patients (TN patients), particularly in the subset with basal phenotype (TN and either EGFR+ or cytokeratins 5/6+). The Luminal A subtype also achieved a significant benefit with FEC-P. The molecular-defined subgroup of TN was clearly predictive of better response to treatment with FEC-P. Luminal A patients had the best prognosis and also have a better outcome with weekly paclitaxel.

Mantle cell lymphoma: transcriptional regulation by microRNAs.

Abstract: Mantle cell lymphoma (MCL) pathogenesis is still partially unexplained. We investigate the importance of microRNA (miRNA) expression as an additional feature that influences MCL pathway deregulation and may be useful for predicting patient outcome. Twenty-three MCL samples, eight cell lines and appropriate controls were screened for their miRNAs and gene expression profiles and DNA copy-number changes. MCL patients exhibit a characteristic signature that includes 117 miRNA (false discovery rate <0.05). Combined analysis of miRNAs and the gene expression profile, paired with bioinformatics target prediction (miRBase and TargetScan), revealed a series of genes and pathways potentially targeted by a small number of miRNAs, including essential pathways for lymphoma survival such as CD40, mitogen-activated protein kinase and NF-κB. Functional validation in MCL cell lines demonstrated NF-κB subunit nuclear translocation to be regulated by the expression of miR-26a. The expression of 12 selected miRNAs was studied by quantitative PCR in an additional series of 54 MCL cases. Univariate analysis identified a single miRNA, miR-20b, whose lack of expression distinguished cases with a survival probability of 56% at 60 months. In summary, using a novel bioinformatics approach, this study identified miRNA changes that contribute to MCL pathogenesis and markers of potential utility in MCL diagnosis and clinical prognostication.