Medical treatments and risk factors for resection surgery in Crohn's disease: results from the Swiss IBD Cohort Study

Background: Surgery has been previously reported to be necessary in up to 80% of Crohn's disease (CD) patients, and up to 65% of patients needed reoperation after 10 years. Prevention of surgery is therefore a particularly important issue for these patients. Treatment options are controversial and data on them are scarce. This study reports medical treatments and main clinical risk factors in CD patients having undergone one or several surgeries. Risks for being free from surgery were also assessed. Methods: Retrospective cohort study, using data from patients included in the Swiss IBD cohort study from November 2006 to July 2011. History of resective surgeries, clinical characteristics and drug regimens were collected through detailed medical records. Univariate and multivariate analyses for clinical and therapeutic factors were performed. Cox regression was made to estimate free-of-surgery risks for different phenotypes and drugs. Results: Out of 1138 CD patients in the cohort, 721 (63.4%) were free of surgery at inclusion; 203 (17.8%) had 1 surgery and 214 (18.8%) >1 surgery. Main risk factors for surgery were disease duration 5-10 years (OR=2.92; p<0.001) and >10 years (OR=10.45; p<0.001), as well as stricturing (OR=8.33; p<0.001) or fistulizing disease (OR=7.34; p<0.001). Risk factors for repeated surgery was disease duration >10 years (OR=2.55; p=0.006) or fistulizing disease (OR=3.79; p<0.001). At inclusion, 107 patients (25.7%) had at least one anti-TNF alpha, 168 (40.3%) at least one immunosuppressive agent, and 41 (9.8%) at least 5-ASA or antibiotics. 64 (15.3%) were not exposed to any medical treatment. Kaplan-Meier curves showed that the risk of being free of surgery was 65% after 10 years, 42% after 20 years and 23% after 40 years. Surgical risks were four resp. five time higher for fistulizing and stricturing phenotypes (Hazard ratio (HR) =4.2; p<0.001; resp. HR=4.7; p<0.001) compared to inflammatory phenotype. Surgical risk was 4 times lower (HR=0.27; p=0.063) in CD patients under anti-TNF alpha compared to those under other or no drugs. Conclusion: The risk of having resective surgery was confirmed to be very high for CD in our cohort. Duration of disease, fistulizing and stricturing disease pattern enhance the risk of surgery. Anti-TNF alpha tends to lower this risk.

Common genetic variation and the control of HIV-1 in humans.

To extend the understanding of host genetic determinants of HIV-1 control, we performed a genome-wide association study in a cohort of 2,554 infected Caucasian subjects. The study was powered to detect common genetic variants explaining down to 1.3% of the variability in viral load at set point. We provide overwhelming confirmation of three associations previously reported in a genome-wide study and show further independent effects of both common and rare variants in the Major Histocompatibility Complex region (MHC). We also examined the polymorphisms reported in previous candidate gene studies and fail to support a role for any variant outside of the MHC or the chemokine receptor cluster on chromosome 3. In addition, we evaluated functional variants, copy-number polymorphisms, epistatic interactions, and biological pathways. This study thus represents a comprehensive assessment of common human genetic variation in HIV-1 control in Caucasians.

Projecte de legalització d'una activitat dedicada a l'explotació ramadera i a la formatgeria artesanal

La integració en una mateixa activitat d'una explotació ramadera ecològica basada en el bestiar cabrú de llet i d'una formatgeria artesanal basada en varietats autòctones de formatge de cabra, permet ocupar un nínxol de mercat encara poc explotat actualment a Catalunya. D'igual manera, la dificultat que tenen actualment molts dels formatgers artesans del país per trobar llet de cabra en quantitats suficients i amb unes mínimes garanties higiènico-sanitàries dificulten l'avanç d'un sector amb molt bones perspectives de futur com és el de la formatgeria artesanal i justifica la necessitat de crear noves explotacions (o reconvertir-ne de ja existents) orientant-les de ple vers l'aprofitament lleter del bestiar cabrú, que és actualment molt reduït en l'àmbit Català. A més d'això, les actuals exigències en el camp del benestar animal així com en el camp de la qualitat i de la seguretat alimentaria, exigeixen a les explotacions ramaderes i a les indústries alimentàries el compliment d'una sèrie de requisits, tan de disseny dels locals i de les instal•lacions, com de control de les activitats i dels productes elaborats, que garanteixin en tot moment la seva correcte gestió i funcionament en aquestes matèries. L'objectiu d'aquest projecte, doncs, és la legalització d'una activitat, que anomenarem “Mas Peirot, S.L.”, dedicada a l'explotació ramadera ecològica de bestiar cabrú de llet i a la formatgeria artesanal de formatge de cabra. És important mencionar que tot i tractar-se d'un projecte de legalització d'una activitat,, també s'hi han contemplat aspectes i detalls relacionats amb l'execució de la mateixa, al tractar-se d'unes obres d'una certa complexitat i considerant que així es tracten amb més detall i rigorositat les actuacions projectades. En concret, en aquest projecte es planifiquen les operacions de rehabilitació de dues naus ramaderes actualment en desús, per tal que puguin destinar-se a l'explotació ramadera de bestiar cabrú i a la formatgeria artesanal, projectant-se així mateix totes les instal•lacions necessàries per tal que a les mencionades naus s'hi puguin desenvolupar les activitats citades. Com a conclusions més importants d'aquest projecte podem dir que amb un cens de 100 caps de bestiar cabrú és possible obtenir una producció mitjana de llet de 32.500 litres anuals, que es corresponen a un volum total de 3.823 quilograms de formatge a l'any (de les tipologies Formatge Garrotxa i Formatge de cabra amb oli, ambdues varietats tradicionals catalanes) obtenint un benefici de 21.389,47 Euros/any durant els primers 15 anys i un benefici de 33.386,39 Euros/any a partir del 16è any, cosa que permetrà recuperar la inversió inicial de 172.716,76 Euros que valen les naus i instal•lacions projectades, en un termini de 8 anys i permetrà, com s'ha dit, ocupar un nínxol de mercat encara poc explotat per la indústria agroalimentària a Catalunya.

Transcatheter aortic valve implantation in failed bioprosthetic surgical valves.

IMPORTANCE: Owing to a considerable shift toward bioprosthesis implantation rather than mechanical valves, it is expected that patients will increasingly present with degenerated bioprostheses in the next few years. Transcatheter aortic valve-in-valve implantation is a less invasive approach for patients with structural valve deterioration; however, a comprehensive evaluation of survival after the procedure has not yet been performed. OBJECTIVE: To determine the survival of patients after transcatheter valve-in-valve implantation inside failed surgical bioprosthetic valves. DESIGN, SETTING, AND PARTICIPANTS: Correlates for survival were evaluated using a multinational valve-in-valve registry that included 459 patients with degenerated bioprosthetic valves undergoing valve-in-valve implantation between 2007 and May 2013 in 55 centers (mean age, 77.6 [SD, 9.8] years; 56% men; median Society of Thoracic Surgeons mortality prediction score, 9.8% [interquartile range, 7.7%-16%]). Surgical valves were classified as small (≤21 mm; 29.7%), intermediate (>21 and <25 mm; 39.3%), and large (≥25 mm; 31%). Implanted devices included both balloon- and self-expandable valves. MAIN OUTCOMES AND MEASURES: Survival, stroke, and New York Heart Association functional class. RESULTS: Modes of bioprosthesis failure were stenosis (n = 181 [39.4%]), regurgitation (n = 139 [30.3%]), and combined (n = 139 [30.3%]). The stenosis group had a higher percentage of small valves (37% vs 20.9% and 26.6% in the regurgitation and combined groups, respectively; P = .005). Within 1 month following valve-in-valve implantation, 35 (7.6%) patients died, 8 (1.7%) had major stroke, and 313 (92.6%) of surviving patients had good functional status (New York Heart Association class I/II). The overall 1-year Kaplan-Meier survival rate was 83.2% (95% CI, 80.8%-84.7%; 62 death events; 228 survivors). Patients in the stenosis group had worse 1-year survival (76.6%; 95% CI, 68.9%-83.1%; 34 deaths; 86 survivors) in comparison with the regurgitation group (91.2%; 95% CI, 85.7%-96.7%; 10 deaths; 76 survivors) and the combined group (83.9%; 95% CI, 76.8%-91%; 18 deaths; 66 survivors) (P = .01). Similarly, patients with small valves had worse 1-year survival (74.8% [95% CI, 66.2%-83.4%]; 27 deaths; 57 survivors) vs with intermediate-sized valves (81.8%; 95% CI, 75.3%-88.3%; 26 deaths; 92 survivors) and with large valves (93.3%; 95% CI, 85.7%-96.7%; 7 deaths; 73 survivors) (P = .001). Factors associated with mortality within 1 year included having small surgical bioprosthesis (≤21 mm; hazard ratio, 2.04; 95% CI, 1.14-3.67; P = .02) and baseline stenosis (vs regurgitation; hazard ratio, 3.07; 95% CI, 1.33-7.08; P = .008). CONCLUSIONS AND RELEVANCE: In this registry of patients who underwent transcatheter valve-in-valve implantation for degenerated bioprosthetic aortic valves, overall 1-year survival was 83.2%. Survival was lower among patients with small bioprostheses and those with predominant surgical valve stenosis.

Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism.

BACKGROUND: Whether the oral factor Xa inhibitor edoxaban can be an alternative to warfarin in patients with venous thromboembolism is unclear. METHODS: In a randomized, double-blind, noninferiority study, we randomly assigned patients with acute venous thromboembolism, who had initially received heparin, to receive edoxaban at a dose of 60 mg once daily, or 30 mg once daily (e.g., in the case of patients with creatinine clearance of 30 to 50 ml per minute or a body weight below 60 kg), or to receive warfarin. Patients received the study drug for 3 to 12 months. The primary efficacy outcome was recurrent symptomatic venous thromboembolism. The principal safety outcome was major or clinically relevant nonmajor bleeding. RESULTS: A total of 4921 patients presented with deep-vein thrombosis, and 3319 with a pulmonary embolism. Among patients receiving warfarin, the time in the therapeutic range was 63.5%. Edoxaban was noninferior to warfarin with respect to the primary efficacy outcome, which occurred in 130 patients in the edoxaban group (3.2%) and 146 patients in the warfarin group (3.5%) (hazard ratio, 0.89; 95% confidence interval [CI], 0.70 to 1.13; P<0.001 for noninferiority). The safety outcome occurred in 349 patients (8.5%) in the edoxaban group and 423 patients (10.3%) in the warfarin group (hazard ratio, 0.81; 95% CI, 0.71 to 0.94; P=0.004 for superiority). The rates of other adverse events were similar in the two groups. A total of 938 patients with pulmonary embolism had right ventricular dysfunction, as assessed by measurement of N-terminal pro-brain natriuretic peptide levels; the rate of recurrent venous thromboembolism in this subgroup was 3.3% in the edoxaban group and 6.2% in the warfarin group (hazard ratio, 0.52; 95% CI, 0.28 to 0.98). CONCLUSIONS: Edoxaban administered once daily after initial treatment with heparin was noninferior to high-quality standard therapy and caused significantly less bleeding in a broad spectrum of patients with venous thromboembolism, including those with severe pulmonary embolism. (Funded by Daiichi-Sankyo; Hokusai-VTE ClinicalTrials.gov number, NCT00986154.).

Biliary atresia: Swiss national study, 1994-2004.

OBJECTIVES: To determine the epidemiology of biliary atresia (BA) in Switzerland, the outcome of the children from diagnosis, and the prognostic factors. PATIENTS AND METHODS: The records of all patients with BA born in Switzerland between January 1994 and December 2004 were analyzed. Survival rates were calculated with the Kaplan-Meier method, and prognostic factors evaluated with the log rank test. Median follow up was 58 months (range, 5-124). RESULTS: BA was diagnosed in 48 children. Incidence was 1 in 17,800 live births (95% confidence interval 1/13,900-1/24,800), without significant regional, annual, or seasonal variation. Forty-three children underwent a Kasai portoenterostomy (PE) in 5 different Swiss pediatric surgery units. Median age at Kasai PE was 68 days (range, 30-126). Four-year survival with native liver after Kasai PE was 37.4%. Liver transplantation (LT) was needed in 31 in 48 children with BA, including 5 patients without previous Kasai PE. Four patients (8%, all born before 2001) died while waiting for LT, and 29 LT were performed in 27 patients (28 in Geneva and 1 in Paris). All of the transplanted patients are alive. Four-year overall BA patient survival was 91.7%. Four-year survival with native liver was 75% in patients who underwent Kasai PE before 46 days, 33% in patients operated on between 46 and 75 days, and 11% in patients operated on after 75 days (P = 0.02). CONCLUSIONS: Overall survival of patients with BA in Switzerland compares favorably with current international standards, whereas results of the Kasai operation could be improved to reduce the need for LTs in infancy and early childhood.

Low income, community poverty and risk of end stage renal disease

BACKGROUND: The risk of end stage renal disease (ESRD) is increased among individuals with low income and in low income communities. However, few studies have examined the relation of both individual and community socioeconomic status (SES) with incident ESRD. METHODS: Among 23,314 U.S. adults in the population-based Reasons for Geographic and Racial Differences in Stroke study, we assessed participant differences across geospatially-linked categories of county poverty [outlier poverty, extremely high poverty, very high poverty, high poverty, neither (reference), high affluence and outlier affluence]. Multivariable Cox proportional hazards models were used to examine associations of annual household income and geospatially-linked county poverty measures with incident ESRD, while accounting for death as a competing event using the Fine and Gray method. RESULTS: There were 158 ESRD cases during follow-up. Incident ESRD rates were 178.8 per 100,000 person-years (105 py) in high poverty outlier counties and were 76.3 /105 py in affluent outlier counties, p trend = 0.06. In unadjusted competing risk models, persons residing in high poverty outlier counties had higher incidence of ESRD (which was not statistically significant) when compared to those persons residing in counties with neither high poverty nor affluence [hazard ratio (HR) 1.54, 95% Confidence Interval (CI) 0.75-3.20]. This association was markedly attenuated following adjustment for socio-demographic factors (age, sex, race, education, and income); HR 0.96, 95% CI 0.46-2.00. However, in the same adjusted model, income was independently associated with risk of ESRD [HR 3.75, 95% CI 1.62-8.64, comparing the < $20,000 income group to the > $75,000 group]. There were no statistically significant associations of county measures of poverty with incident ESRD, and no evidence of effect modification. CONCLUSIONS: In contrast to annual family income, geospatially-linked measures of county poverty have little relation with risk of ESRD. Efforts to mitigate socioeconomic disparities in kidney disease may be best appropriated at the individual level.

Pretherapeutic gamma-glutamyltransferase is an independent prognostic factor for patients with renal cell carcinoma.

BACKGROUND: Gamma-glutamyltransferase (GGT) regulates apoptotic balance and promotes cancer progression and invasion. Higher pretherapeutic GGT serum levels have been associated with worse outcomes in various malignancies, but there are no data for renal cell carcinoma (RCC). METHODS: Pretherapeutic GGT serum levels and clinicopathological parameters were retrospectively evaluated in 921 consecutive RCC patients treated with nephrectomy at a single institution between 1998 and 2013. Gamma-glutamyltransferase was analysed as continuous and categorical variable. Associations with RCC-specific survival were assessed with Cox proportional hazards models. Discrimination was measured with the C-index. Decision-curve analysis was used to evaluate the clinical net benefit. The median postoperative follow-up was 45 months. RESULTS: Median pretherapeutic serum GGT level was 25 U l(-1). Gamma-glutamyltransferase levels increased with advancing T (P<0.001), N (P=0.006) and M stages (P<0.001), higher grades (P<0.001), and presence of tumour necrosis (P<0.001). An increase of GGT by 10 U l(-1) was associated with an increase in the risk of death from RCC by 4% (HR 1.04, P<0.001). Based on recursive partitioning-based survival tree analysis, we defined four prognostic categories of GGT: normal low (<17.5 U l(-1)), normal high (17.5 to <34.5 U l(-1)), elevated (34.5 to <181.5 U l(-1)), and highly elevated (⩾181.5 U l(-1)). In multivariable analyses that adjusted for the effect of standard features, both continuously and categorically coded GGT were independent prognostic factors. Adding GGT to a model that included standard features increased the discrimination by 0.9% to 1.8% and improved the clinical net benefit. CONCLUSIONS: Pretherapeutic serum GGT is a novel and independent prognostic factor for patients with RCC. Stratifying patients into prognostic subgroups according to GGT may be used for patient counselling, tailoring surveillance, individualised treatment planning, and clinical trial design.

Do different measures of early life socioeconomic circumstances predict adult mortality? Evidence from the British Whitehall II and French GAZEL studies

BACKGROUND: Father's occupational position, education and height have all been used to examine the effects of adverse early life socioeconomic circumstances on health, but it remains unknown whether they predict mortality equally well. METHODS: We used pooled data on 18,393 men and 7060 women from the Whitehall II and GAZEL cohorts to examine associations between early life socioeconomic circumstances and all-cause and cause-specific mortality. RESULTS: During the 20-y follow-up period, 1487 participants died. Education had a monotonic association with all mortality outcomes; the age, sex and cohort-adjusted HR for the lowest versus the highest educational group was 1.45 (95% CI 1.24 to 1.69) for all-cause mortality. There was evidence of a U-shaped association between height and all-cause, cancer and cardiovascular mortality robust to adjustment for the other indicators (HR 1.41, 95% CI 1.03 to 1.93 for those shorter than average and HR 1.36, 95% CI 0.98 to 1.88 for those taller than average for cardiovascular mortality). Greater all-cause and cancer mortality was observed in participants whose father's occupational position was manual rather than non-manual (HR 1.11, 95% CI 1.00 to 1.23 for all-cause mortality), but the risks were attenuated after adjusting for education and height. CONCLUSIONS: The association between early life socioeconomic circumstances and mortality depends on the socioeconomic indicator used and the cause of death examined. Height is not a straightforward measure of early life socioeconomic circumstances as taller people do not have a health advantage for all mortality outcomes.

Prognostic significance of deep vein thrombosis in patients presenting with acute symptomatic pulmonary embolism.

RATIONALE: Concomitant deep vein thrombosis (DVT) in patients with acute pulmonary embolism (PE) has an uncertain prognostic significance. OBJECTIVES: In a cohort of patients with PE, this study compared the risk of death in those with and those without concomitant DVT. METHODS: We conducted a prospective cohort study of outpatients diagnosed with a first episode of acute symptomatic PE. Patients underwent bilateral lower extremity venous compression ultrasonography to assess for concomitant DVT. MEASUREMENTS AND MAIN RESULTS: The primary study outcome, all-cause mortality, and the secondary outcome of PE-specific mortality were assessed during the 3 months of follow-up after PE diagnosis. Multivariate Cox proportional hazards regression was done to adjust for significant covariates. Of 707 patients diagnosed with PE, 51.2% (362 of 707) had concomitant DVT and 10.9% (77 of 707) died during follow-up. Patients with concomitant DVT had an increased all-cause mortality (adjusted hazard ratio [HR], 2.05; 95% confidence interval [CI], 1.24 to 3.38; P = 0.005) and PE-specific mortality (adjusted HR, 4.25; 95% CI, 1.61 to 11.25; P = 0.04) compared with those without concomitant DVT. In an external validation cohort of 4,476 patients with acute PE enrolled in the international multicenter RIETE Registry, concomitant DVT remained a significant predictor of all-cause (adjusted HR, 1.66; 95% CI, 1.28 to 2.15; P < 0.001) and PE-specific mortality (adjusted HR, 2.01; 95% CI, 1.18 to 3.44; P = 0.01). CONCLUSIONS: In patients with a first episode of acute symptomatic PE, the presence of concomitant DVT is an independent predictor of death in the ensuing 3 months after diagnosis. Assessment of the thrombotic burden should assist with risk stratification of patients with acute PE.

Quality of care and survival of haemodialysed patients in western Switzerland.

BACKGROUND: Many factors affect survival in haemodialysis (HD) patients. Our aim was to study whether quality of clinical care may affect survival in this population, when adjusted for demographic characteristics and co-morbidities. METHODS: We studied survival in 553 patients treated by chronic HD during March 2001 in 21 dialysis facilities in western Switzerland. Indicators of quality of care were established for anaemia control, calcium and phosphate product, serum albumin, pre-dialysis blood pressure (BP), type of vascular access and dialysis adequacy (spKt/V) and their baseline values were related to 3-year survival. The modified Charlson co-morbidity index (including age) and transplantation status were also considered as a predictor of survival. RESULTS: Three-year survival was obtained for 96% of the patients; 39% (211/541) of these patients had died. The 3-year survival was 50, 62 and 69%, respectively, in patients who had 0-2, 3 and >or=4 fulfilled indicators of quality of care (test for linear trend, P < 0.001). In a Cox multivariate analysis model, the absence of transplantation, a higher modified Charlson's score, decreased fulfilment of indicators of good clinical care and low pre-dialysis systolic BP were independent predictors of death. CONCLUSION: Good clinical care improves survival in HD patients, even after adjustment for availability of transplantation and co-morbidities.

Cáncer de laringe en pacientes menores de 40 años comparado con mayores de 40 años: análisis de pares [Laryngeal cancer in patients younger vs older than 40 years old: a matched-paired analysis].

BACKGROUND: To compare clinical and demographic data between laryngeal cancer patients younger and older than 40 years old. METHODS: Is a matched-paired study, realized from 1989 to 2002. We selected 500 laryngeal cancer patients treated in the National Cancer Institute of Mexico. Fifteen cases of patients younger than 40 years that accomplished inclusion criteria were identified, pair-matched and compared by clinical stage with 33 patients older than 40 years. We analyzed demographic factors and disease-free and Overall Survival by Kaplan-Meier method. RESULTS: We included 9 male and 6 female patients with a mean age of 34 years in contrast to a mean age of 62 years in the comparison group. Four cases in clinical stage I, none clinical stage II, 6 in stage III and 5 in stage IV were included in the younger group and compared to 8 patients in stage I, 15 in stage III and 10 in stage IV in the older group. No differences in demographic variables or lifestyle habits were found. All patients in stage I, are alive in both groups. Disease-free survival not show any differences when comparing stages III and IV (p=NS). Mean disease-free survival was 66 months and mean overall survival was 83 months in the younger group. CONCLUSION: Laryngeal carcinoma is rare in patients younger than 40 years. No gender, clinical or prognostic differences could be identified among the two groups. The prognosis of these patients seems to be only determined by the initial clinical stage.

External irradiation with or without long-term androgen suppression for prostate cancer with high metastatic risk: 10-year results of an EORTC randomised study.

BACKGROUND: We did a randomised phase 3 trial assessing the benefit of addition of long-term androgen suppression with a luteinising-hormone-releasing hormone (LHRH) agonist to external irradiation in patients with prostate cancer with high metastatic risk. In this report, we present the 10-year results. METHODS: For this open-label randomised trial, eligible patients were younger than 80 years and had newly diagnosed histologically proven T1-2 prostatic adenocarcinoma with WHO histological grade 3 or T3-4 prostatic adenocarcinoma of any histological grade, and a WHO performance status of 0-2. Patients were randomly assigned (1:1) to receive radiotherapy alone or radiotherapy plus immediate androgen suppression. Treatment allocation was open label and used a minimisation algorithm with institution, clinical stage of the disease, results of pelvic-lymph-node dissection, and irradiation fields extension as minimisation factors. Patients were irradiated externally, once a day, 5 days a week, for 7 weeks to a total dose of 50 Gy to the whole pelvis, with an additional 20 Gy to the prostate and seminal vesicles. The LHRH agonist, goserelin acetate (3·6 mg subcutaneously every 4 weeks), was started on the first day of irradiation and continued for 3 years; cyproterone acetate (50 mg orally three times a day) was given for 1 month starting a week before the first goserelin injection. The primary endpoint was clinical disease-free survival. Analysis was by intention to treat. The trial is registered at ClinicalTrials.gov, number NCT00849082. FINDINGS: Between May 22, 1987, and Oct 31, 1995, 415 patients were randomly assigned to treatment groups and were included in the analysis (208 radiotherapy alone, 207 combined treatment). Median follow-up was 9·1 years (IQR 5·1-12·6). 10-year clinical disease-free survival was 22·7% (95% CI 16·3-29·7) in the radiotherapy-alone group and 47·7% (39·0-56·0) in the combined treatment group (hazard ratio [HR] 0·42, 95% CI 0·33-0·55, p<0·0001). 10-year overall survival was 39·8% (95% CI 31·9-47·5) in patients receiving radiotherapy alone and 58·1% (49·2-66·0) in those allocated combined treatment (HR 0·60, 95% CI 0·45-0·80, p=0·0004), and 10-year prostate-cancer mortality was 30·4% (95% CI 23·2-37·5) and 10·3% (5·1-15·4), respectively (HR 0·38, 95% CI 0·24-0·60, p<0·0001). No significant difference in cardiovascular mortality was noted between treatment groups both in patients who had cardiovascular problems at study entry (eight of 53 patients in the combined treatment group had a cardiovascular-related cause of death vs 11 of 63 in the radiotherapy group; p=0·60) and in those who did not (14 of 154 vs six of 145; p=0·25). Two fractures were reported in patients allocated combined treatment. INTERPRETATION: In patients with prostate cancer with high metastatic risk, immediate androgen suppression with an LHRH agonist given during and for 3 years after external irradiation improves 10-year disease-free and overall survival without increasing late cardiovascular toxicity.

Applications of the bootstrap to survival analysis

En este trabajo se revisan algunas de las aplicaciones clásicas del bootstrap al análisis de la supervivencia. Se consideran en primer lugar el estimador bootstrap de la varianza y el estimador de la mediana corregido para el sesgo del estimador de Kaplan-Meier de la función de supervivencia. A continuación se consideran algunos aspectos mas recientes, tales como métodos para construir bandas de confianza para el estimador de la funcidn de supervivencia y contrastes aproximados para la comparación de funciones de supervivencia. En ambas situaciones el bootstrap resulta de gran utilidad para la aproximación de 10s valores críticos necesarios.

Added prognostic value of myocardial blood flow quantitation in rubidium-82 positron emission tomography imaging.

AIMS: We studied the respective added value of the quantitative myocardial blood flow (MBF) and the myocardial flow reserve (MFR) as assessed with (82)Rb positron emission tomography (PET)/CT in predicting major adverse cardiovascular events (MACEs) in patients with suspected myocardial ischaemia. METHODS AND RESULTS: Myocardial perfusion images were analysed semi-quantitatively (SDS, summed difference score) and quantitatively (MBF, MFR) in 351 patients. Follow-up was completed in 335 patients and annualized MACE (cardiac death, myocardial infarction, revascularization, or hospitalization for congestive heart failure or de novo stable angor) rates were analysed with the Kaplan-Meier method in 318 patients after excluding 17 patients with early revascularizations (<60 days). Independent predictors of MACEs were identified by multivariate analysis. During a median follow-up of 624 days (inter-quartile range 540-697), 35 MACEs occurred. An annualized MACE rate was higher in patients with ischaemia (SDS >2) (n = 105) than those without [14% (95% CI = 9.1-22%) vs. 4.5% (2.7-7.4%), P < 0.0001]. The lowest MFR tertile group (MFR <1.8) had the highest MACE rate [16% (11-25%) vs. 2.9% (1.2-7.0%) and 4.3% (2.1-9.0%), P < 0.0001]. Similarly, the lowest stress MBF tertile group (MBF <1.8 mL/min/g) had the highest MACE rate [14% (9.2-22%) vs. 7.3% (4.2-13%) and 1.8% (0.6-5.5%), P = 0.0005]. Quantitation with stress MBF or MFR had a significant independent prognostic power in addition to semi-quantitative findings. The largest added value was conferred by combining stress MBF to SDS. This holds true even for patients without ischaemia. CONCLUSION: Perfusion findings in (82)Rb PET/CT are strong MACE outcome predictors. MBF quantification has an added value allowing further risk stratification in patients with normal and abnormal perfusion images.