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Kinds of Hazard Ratio Selected AbstractsSafety of sertindole versus risperidone in schizophrenia: principal results of the sertindole cohort prospective study (SCoP)ACTA PSYCHIATRICA SCANDINAVICA, Issue 5 2010S. H. L. Thomas Thomas SHL, Drici MD, Hall GC, Crocq MA, Everitt B, Lader MH, Le Jeunne C, Naber D, Priori S, Sturkenboom M, Thibaut F, Peuskens J, Mittoux A, Tanghøj P, Toumi M, Moore ND, Mann RD. Safety of sertindole versus risperidone in schizophrenia: principal results of the sertindole cohort prospective study (SCoP) Objective:, To explore whether sertindole increases all-cause mortality or cardiac events requiring hospitalization, compared with risperidone. Method:, Multinational randomized, open-label, parallel-group study, with blinded classification of outcomes, in 9858 patients with schizophrenia. Results:, After 14147 person-years, there was no effect of treatment on overall mortality (sertindole 64, risperidone 61 deaths, Hazard Ratio (HR) = 1.12 (90% CI: 0.83, 1.50)) or cardiac events requiring hospitalization [sertindole 10, risperidone 6, HR = 1.73 (95% CI: 0.63, 4.78)]: Of these, four were considered arrhythmia-related (three sertindole, one risperidone). Cardiac mortality was higher with sertindole (Independent Safety Committee (ISC): 31 vs. 12, HR=2.84 (95% CI: 1.45, 5.55), P = 0.0022; Investigators 17 vs. 8, HR=2.13 (95% CI: 0.91, 4.98), P = 0.081). There was no significant difference in completed suicide, but fewer sertindole recipients attempted suicide (ISC: 68 vs. 78, HR=0.93 (95% CI: 0.66, 1.29), P = 0.65; Investigators: 43 vs. 65, HR=0.67 (95% CI: 0.45, 0.99), P = 0.044). Conclusion:, Sertindole did not increase all-cause mortality, but cardiac mortality was higher and suicide attempts may be lower with sertindole. [source] Long-term follow-up of nevirapine-treated patients in a single-centre cohortHIV MEDICINE, Issue 8 2009M Colafigli Objectives We reviewed the safety and efficacy of nevirapine (NVP)-based therapy in all patients initiating NVP-containing combined antiretroviral therapy [cART (,3 drugs)] in our clinic since 1994. Methods Patient characteristics and laboratory values from the start of the NVP-based cART regimen to the last available follow-up or to NVP discontinuation were retrieved from an observational database. Results Five hundred and seventy-three patients were treated with NVP-based cART for a median of 18.4 (range 0.1,128.8) months. The 1-year cumulative estimated probability of discontinuing NVP-containing regimens for toxicity was 0.203. Only 1.9% developed a grade 3 alanine aminotransferase (ALT) elevation. Significant increases in high-density lipoprotein cholesterol were observed up to month 12 except in treatment-naïve patients, where the increase was limited to 3 months. Discontinuation because of cutaneous reaction was predicted independently by female gender [Hazard Ratio (HR) 3.21, P<0.001] and Centers for Disease Control class C (HR 0.50, P=0.012). Discontinuation because of liver toxicity was predicted independently by anti-hepatitis C virus positivity (HR 3.84, P<0.001). In patients starting NVP-containing cART with undetectable viral loads, the 5-year estimated probability of viral load >400 HIV-1 RNA copies/mL was 0.34. Conclusions Long-term follow-up with an NVP-containing cART showed a low rate of discontinuation caused by liver toxicity and the maintenance of virological suppression in patients switched with undetectable viral loads. [source] Are MADIT II Criteria for Implantable Cardioverter Defibrillator Implantation Appropriate for Chinese Patients?JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 3 2010CHUNG-WAH SIU M.B.B.S. MADIT II Criteria for Implantable Cardioverter.,Background: MADIT-II demonstrated that prophylactic implantation of an implantable cardioverter-defibrillator (ICD) device prevents sudden cardiac death (SCD) in patients with myocardial infarction (MI) and impaired left ventricular ejection fraction (LVEF). It remains unclear whether the MADIT-II criteria for ICD implantation are appropriate for Chinese patients. Methods and Results: We compared the clinical characteristics and outcome for a cohort of consecutive Chinese patients who satisfied MADIT-II criteria for ICD implantation with the original published MADIT-II population. Seventy consecutive patients who satisfied MADIT-II criteria but did not undergo ICD implantation (age: 67 years, male: 77%) were studied. Their baseline demographics were comparable with the original MADIT-II cohort with the exception of a higher incidence of diabetes mellitus. After follow-up of 35 months, most deaths (78%) were due to cardiac causes (72% due to SCD). The 2-year SCD rate (10.0%) was comparable with that of the MADIT-II conventional group (12.1%), but higher than the MADIT-II defibrillator group (4.9%). Similarly, the 2-year non-SCD rate was 3.0%, also comparable with the MADIT-II conventional group (4.6%), but lower than the MADIT-II defibrillator group (7.0%). Cox regression analysis revealed that advance NYHA function class (Hazard Ratio [HR]: 3.5, 95% Confidence Interval [CI]: 1.48,8.24, P = 0.004) and the lack of statin therapy (HR: 3.7, 95%CI: 1.35,10.17, P = 0.011) were independent predictors for mortality in the MADIT-II eligible patients. Conclusion: Chinese patients who satisfy MADIT-II criteria for ICD implantation are at similar risk of SCD and non-SCD as the original MADIT-II subjects. Implantation of an ICD in Chinese patients is appropriate. (J Cardiovasc Electrophysiol, Vol. 21, pp. 231,235, March 2010) [source] Obesity As a Risk Factor for Sustained Ventricular Tachyarrhythmias in MADIT II PatientsJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 2 2007GRZEGORZ PIETRASIK M.D. Background: Obesity, as defined by body mass index ,30 kg/m2, has been shown to be a risk factor for cardiovascular disease. However, data on the relationship between body mass index (BMI) and the risk of ventricular arrhythmias and sudden cardiac death are limited. The aim of this study was to evaluate the risk of ventricular tachyarrhythmias and sudden death by BMI in patients after myocardial infarction with severe left ventricular dysfunction. Methods: The risk of appropriate defibrillator therapy for ventricular tachycardia or ventricular fibrillation (VT/VF) by BMI status was analyzed in 476 nondiabetic patients with left ventricular dysfunction who received an implantable cardioverter defibrillator (ICD) in the Multicenter Automatic Defibrillator Implantation Trial-II (MADIT II). Results: Mean BMI was 27 ± 5 kg/m2. Obese patients comprised 25% of the study population. After 2 years of follow-up, the cumulative rates of appropriate ICD therapy for VT/VF were 39% in obese and 24% in nonobese patients, respectively (P = 0.014). In multivariate analysis, there was a significant 64% increase in the risk for appropriate ICD therapy among obese patients as compared with nonobese patients, which was attributed mainly to an 86% increase in the risk of appropriate ICD shocks (P = 0.006). Consistent with these results, the risk of the combined endpoint of appropriate VT/VF therapy or sudden cardiac death (SCD) was also significantly increased among obese patients (Hazard Ratio 1.59; P = 0.01). Conclusions: Our findings suggest that in nondiabetic patients with ischemic left ventricular dysfunction, a BMI ,30 kg/m2 is an independent risk factor for ventricular tachyarrhythmias. [source] Laboratory and clinical outcomes of pharmacogenetic vs. clinical protocols for warfarin initiation in orthopedic patientsJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 10 2008P. A. LENZINI Summary.,Background:,Warfarin is commonly prescribed for prophylaxis and treatment of thromboembolism after orthopedic surgery. During warfarin initiation, out-of-range International Normalized Ratio (INR) values and adverse events are common. Methods:,In orthopedic patients beginning warfarin therapy, we developed and prospectively validated pharmacogenetic and clinical dose refinement algorithms to revise the estimated therapeutic dose after 4 days of therapy. Results:,The pharmacogenetic algorithm used the cytochrome P450 (CYP) 2C9 genotype, smoking status, peri-operative blood loss, liver disease, INR values and dose history to predict the therapeutic dose. The R2 was 82% in a derivation cohort (n = 86) and 70% when used prospectively (n = 146). The R2 of the clinical algorithm that used INR values and dose history to predict the therapeutic dose was 57% in a derivation cohort (n = 178) and 48% in a prospective validation cohort (n = 146). In 1 month of prospective follow-up, the percent time spent in the therapeutic range was 7% higher (95% CI: 2.7,11.7) in the pharmacogenetic cohort. The risk of a laboratory or clinical adverse event was also significantly reduced in the pharmacogenetic cohort (Hazard Ratio 0.54; 95% CI: 0.30,0.97). Conclusions:,Warfarin dose adjustments that incorporate genotype and clinical variables available after four warfarin doses are accurate. In this non-randomized, prospective study, pharmacogenetic dose refinements were associated with more time spent in the therapeutic range and fewer laboratory or clinical adverse events. To facilitate gene-guided warfarin dosing we created a non-profit website, http://www.WarfarinDosing.org. [source] Long-term survival of patients with unresectable hepatocellular carcinoma treated with transcatheter arterial chemoinfusionALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2007B. Y. HA Summary Background Transcatheter arterial chemoembolization (TACE) has become one of the most common treatments for unresectable hepatocellular carcinoma. Published studies of TACE report a 5,16% risk of serious complications. Compared with TACE, transcatheter arterial chemoinfusion (TACI) may have similar efficacy and fewer side effects. Aim To examine the clinical outcomes of TACI. Methods We performed a retrospective cohort study of 345 consecutive TACI cases in 165 patients performed at a single United States medical center between 1998 and 2002. Primary outcomes were tumour response and survival rates. Results Only seven patients were hospitalized for more than 24 h after the procedure, and only three patients had worsening of liver function within 30 days of TACI. Survival was significantly poorer for patients with tumour-node-metastasis (TNM) IV compared to those with TNM I,III and also for patients with Child's class B/C vs. A. Following adjustment for age, gender, ethnicity and aetiology of liver diseases, independent predictors of poor survival were Child's class B/C [Hazard Ratio (HR) = 1.69, P = 0.024] and TNM IV staging (HR = 1.63, P = 0.014). Conclusions TACI appears to be safe and effective for unresectable hepatocellular carcinoma with TNM stage I,III; randomized controlled trials are needed to compare TACI to TACE. [source] ZAP-70 expression is associated with increased risk of autoimmune cytopenias in CLL patients,AMERICAN JOURNAL OF HEMATOLOGY, Issue 7 2010Roberta Zanotti Autoimmune cytopenias (AIC) are frequent in chronic lymphocytic leukemia (CLL) patients, but risk factors and prognostic relevance of these events are controversial. Data about the influence on AIC of biological prognostic markers, as ZAP-70, are scanty. We retrospectively evaluated AIC in 290 CLL patients tested for ZAP-70 expression by immunohistochemistry on bone marrow biopsy at presentation. They were 185 men, median age 63 years, 77.9% Binet stage A, 17.6% B and 4.5% C. AIC occurred in 46 patients (16%): 31 autoimmune hemolytic anemias, 10 autoimmune thrombocytopenias, four Evans syndromes, and one pure red cell aplasia. Of the 46 cases of AIC, 37 (80%) occurred in ZAP-70 positive patients and nine (20%) in ZAP-70 negatives. ZAP-70 expression [Hazard Ratio (HR) = 7.42; 95% confidence interval (CI): 2.49,22.05] and age >65 years (HR = 5.41; 95% CI: 1.67,17.49) resulted independent risk factors for AIC. Among the 136 patients evaluated both for ZAP-70 expression and IGHV status, the occurrence of AIC was higher in ZAP-70 positive/IGHV unmutated cases (35%) than in patients ZAP-70 negative/IGHV mutated (6%) or discordant for the two parameters (4%; P < 0.0001). In ZAP-70 positive patients, occurrence of AIC negatively influenced survival (HR = 1.75; 95% CI: 1.06,2.86). The high risk of developing AIC in ZAP-70 positive CLL, particularly when IGHV unmutated, should be considered in the clinical management. Am. J. Hematol. 2010. © 2010 Wiley-Liss, Inc. [source] Inflammation in Areas of Tubular Atrophy in Kidney Allograft Biopsies: A Potent Predictor of Allograft FailureAMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2010R. B. Mannon The Banff scoring schema provides a common ground to analyze kidney transplant biopsies. Interstitial inflammation (i) and tubulitis (t) in areas of viable tissue are features in scoring acute rejection, but are excluded in areas of tubular atrophy (TA). We studied inflammation and tubulitis in a cohort of kidney transplant recipients undergoing allograft biopsy for new-onset late graft dysfunction (N = 337). We found inflammation (,iatr') and tubulitis (,tatr') in regions of fibrosis and atrophy to be strongly correlated with each other (p < 0.0001). Moreover, iatr was strongly associated with death-censored graft failure when compared to recipients whose biopsies had no inflammation, even after adjusting for the presence of interstitial fibrosis (Hazard Ratio = 2.31, [1.10,4.83]; p = 0.0262) or TA (hazard ratio = 2.42, [1.16,5.08]; p = 0.191), serum creatinine at the time of biopsy, time to biopsy and i score. Further, these results did not qualitatively change after additional adjustments for C4d staining or donor specific antibody. Stepwise regression identified the most significant markers of graft failure which include iatr score. We propose that a more global assessment of inflammation in kidney allograft biopsies to include inflammation in atrophic areas may provide better prognostic information. Phenotypic characterization of these inflammatory cells and appropriate treatment may ameliorate late allograft failure. [source] Validity of medication-based co-morbidity indices in the Australian elderly populationAUSTRALIAN AND NEW ZEALAND JOURNAL OF PUBLIC HEALTH, Issue 2 2009Agnes Vitry Abstract Objectives: To determine the validity of two medication-based co-morbidity indices, the Medicines Disease Burden Index (MDBI) and Rx-Risk-V in the Australian elderly population. Methods: In Phase I, the sensitivity and specificity of both indices were determined in 767 respondents from wave 6 of the Australian Longitudinal Study of Ageing (ALSA). Medication-defined index disease categories were compared to self-reported medical conditions. Correlation with self-rated health was examined and Cox proportional hazards models were used to assess the predictive validity for mortality. Phase II verified the predictive ability of Rx-Risk-V in a sample of 213,191 veterans from Australian Department of Veterans' Affairs (DVA) database. Results: MDBI and Rx-Risk-V scores could be calculated for 28% and 73% of the ALSA sample respectively. Both indices had high specificities and low to moderate sensitivities compared to self-reported medical conditions. Total weighted scores were significantly related to self-rated health (p<0.001). Both indices were predictive of mortality (Hazard Ratio (HR) =3.690 (95% CI 2.264-6.015) for MDBI and HR 1.079 (95% CI 1.045-1.114) for Rx-Risk-V. The predictive validity for mortality of Rx-Risk-V was confirmed using DVA data (HR= 1.090, 95% CI 1.088-1.092). Conclusions: Medication-based co-morbidity indices Rx-Risk-V and MDBI are valid measures of co-morbidity. However, Rx-Risk-V detects more comorbidity in the Australian elderly population and is likely to be a more suitable index to use in administrative datasets, particularly where studies include large numbers of outpatients. [source] Non-therapeutic risk factors for onset of tardive dyskinesia in schizophrenia: A meta-analysis,,MOVEMENT DISORDERS, Issue 16 2009Diederik E. Tenback MD Abstract A meta-analysis of prospective studies with schizophrenia patients was conducted to examine whether the evidence exists for risk factors for the emergence of Tardive Dyskinesia (TD) in schizophrenia. A computer assisted Medline/PubMed and Embase search was conducted in January 2008 for the years 1985,2007. Selected were truly prospective studies of incident cases of TD in a population with at least 80% patients with schizophrenia. Measures of relative risk were collected from the individual studies, either directly or by calculating the relative risk from the cox- or logistic regression coefficient provided in the article. Hazard Ratio's and Odds Ratio's were pooled using fixed and random effect models in case of multiple studies using the same measure of risk and outcome. Only eight studies satisfied the inclusion criteria reporting on 25 different single estimate risk factors. Of 25 risk factors, six concerned replicated estimates suitable for meta-analysis. Of these, non-white ethnic group and early extrapyramidal symptoms qualified as risk factors for the emergence of TD in schizophrenia. The association with older age was suggestive but inconclusive. Despite many reported risk factors for TD in schizophrenia, little conclusive evidence exists to corroborate this. However, the fact that early EPS predicts onset of TD has important clinical and research implications. © 2009 Movement Disorder Society [source] Staging of esophageal carcinoma: Length of tumor and number of involved regional lymph nodes.JOURNAL OF SURGICAL ONCOLOGY, Issue 5 2006Are these independent prognostic factors? Abstract Background and Objectives New potential prognostic indicators aside from the TNM classification have been proposed. The aim of this study was to analyze the prognostic relevance of tumor length as well as number of involved regional lymph nodes (LNM) in patients with esophageal carcinoma. Methods Two hundred thirteen patients with esophageal carcinoma (116 squamous cell- and 97 adenocarcinoma) were included in this study. Treatment of choice was subtotal en bloc esophagectomy including "2-field" lymphadenectomy. The median number of examined lymph nodes (LNs) was 28. Eighty patients (38%) received preoperative radio-chemotherapy according to a standardized protocol. Histopathology consisted of tumor stage, residual tumor, grading, and number of examined and involved LN. Univariate and multivariate prognostic values were calculated. Results Length of tumor correlated with pT/ypT-category (P,<,0.01). Univariate but not multivariate analysis showed better survival for tumors ,3 cm (P,<,0.05). Patients with 1,5 LNM had significantly better prognoses than those with more than 5 LNM (Hazard ratio 2.7, 95% CI,=,1.7,4.2) (P,<,0.01). Patients without LNM and more than 15 examined LN showed significantly better prognosis than those with fewer examined LN (Hazard ratio,=,0.3, 95% CI,=,0.1,0.6) (P,<,0.01). Conclusions A revision of the TNM classification for esophageal carcinoma should subdivide the pN1-category according to the number of LNM. J. Surg. Oncol. 2006;94:355,363. © 2006 Wiley-Liss, Inc. [source] Increased Ventricular Ectopic Activity in Relation to C-Reactive Protein, and NT-Pro-Brain Natriuretic Peptide in Subjects With No Apparent Heart DiseasePACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 11 2006AHMAD SAJADIEH M.D. Background: Subjects with frequent ventricular premature complexes (VPC) and no apparent heart disease make a heterogenic group with regard to prognosis. Some biomarkers have recently proved useful in risk stratification in different heart diseases. We examined prognostic impact of NT-Pro-brain natriuretic peptide (NT-Pro BNP), and C-reactive protein (CRP) in relation to frequent VPC in subjects with no apparent heart disease. Methods: Six hundred seventy-eight healthy subjects between 55 and 75 years of age with no history of cardiovascular disease were included in the study. All were tested with fasting laboratory testing and 48-hour ambulatory ECG monitoring. Frequent VPC was defined as VPC ,30/hour. Results: In 56 subjects (8%) with frequent VPC the prognosis was much poorer compared to those without frequent VPC (Hazard ratio and 95% CI: 2.3;1.2,4.4, P = 0.01), after adjustment for conventional risk factors. In subjects with frequent VPC increased levels of CRP (above 2.5 ,g/mL) was the only factor among the tested biomarkers, which was associated with a poor prognosis. Taking subjects without frequent VPC as reference, the hazard ratio and 95% CI for subjects with frequent VPC and increased CRP was 3.6;1.8,7.1, P = 0.0004, and for those with frequent VPC and normal CRP 0.8;0.2,3.5, P = 0.83, after correction for conventional risk factors. Conclusions: Among middle-aged and elderly subjects with no apparent heart disease and frequent VPCs, a CRP value ,2.5 ,g/mL is associated with a significantly higher risk of death and acute myocardial infarction. These subjects deserve primary prevention measures and further work up for structural heart disease. [source] Survival in surgically treated, nodal positive prostate cancer patients is predicted by histopathological characteristics of the primary tumor and its lymph node metastases ,THE PROSTATE, Issue 4 2009Achim Fleischmann Abstract BACKGROUND Histopathological risk factors for survival stratification of surgically treated nodal positive prostate cancer patients are poorly defined as reflected by only one category for nodal metastases. METHODS We evaluated biochemical recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS) in 102 nodal positive, hormone treatment-naïve prostate cancer patients (median age: 65 years, range: 45,75 years; median follow-up 7.7 years, range: 1.0,15.9 years) who underwent radical prostatectomy and standardized extended lymphadenectomy. RESULTS A significant stratification was possible, with the Gleason score of the primary and virtually all nodal parameters favoring patients with better differentiated primaries and metastases, lower nodal tumor burden, and without extranodal extension of metastases. In multivariate analyses, diameter of the largest metastasis (,10 mm vs. >10 mm) was the strongest independent predictor for RFS (P,<,0.001), DSS (P,<,0.001), and OS (P,<,0.001) with a more than quadrupled relative risk of cancer related deaths for patients with larger metastases (Hazard ratio: 4.2, Confidence interval: 2.0,8.9; 5-year RFS/DSS/OS: 18%/57%/54%). The highest 5-year survival rates were seen in patients with micrometastases only (RFS/DSS/OS: 47%/94%/94%). CONCLUSION The TNM classification's current allocation of only one category for nodal metastases in prostate cancers is unsatisfactory since subgroups with significantly different prognoses can be identified. The diameter of the patient's largest metastasis (,10 mm vs. >10 mm) should be used for substaging because of its independent prognostic value. The substage "micrometastasis only" is also useful in nodal positive prostate cancer since it designates the subgroup with the most favorable outcome. Prostate 69:352,362, 2009. © 2008 Wiley-Liss, Inc. [source] Impact of laparoscopic surgery on the long-term outcomes for patients with rectal cancerANZ JOURNAL OF SURGERY, Issue 11 2009Jun-Gi Kim Abstract Background:, This 20-year retrospective study compared the results of laparoscopic surgery with open surgery for patients with rectal cancer to evaluate the impact of laparoscopic surgery on long-term oncological outcomes for rectal cancer. Methods:, We analysed survival data collected over 20 years for patients with rectal cancer (n= 407) according to surgical methods and tumour stage between those treated with laparoscopic surgery (n= 272) and those with open surgery (n= 135). Clinical factors were analysed to ascertain possible risk factors that might have been associated with survival from and recurrence of rectal cancer. A multivariate analysis was applied by using Cox's regression model to determine the impact of laparoscopic surgery on long-term oncological outcomes. Results:, Overall survival, disease-specific survival and disease-free survival rates were statistically higher in the laparoscopic group than in the open-surgery group. The incidence of local recurrence in the laparoscopic group (7.9%; 95% confidence intervals (CI), 4.2,11.5) was significantly lower than that for the open-surgery group (30.2%; 95% CI, 21.0,39.3; P < 0.001). By using a multivariate analysis, laparoscopic surgery for rectal cancer appeared not to be an independent factor for disease-specific survival or disease-free survival. However, the laparoscopic surgery was an independent factor associated with reduced local recurrence (Hazard ratio (HR), 3.408; 95% CI, 1.890,6.149; P < 0.001). Conclusion:, Laparoscopic surgery did not adversely affect the long-term oncological outcome for patients with rectal cancer. [source] Cytogenetic abnormalities in multiple myeloma: poor prognosis linked to concomitant detection in random and focal lesion bone marrow samples and associated with high-risk gene expression profileBRITISH JOURNAL OF HAEMATOLOGY, Issue 5 2009Yiming Zhou Summary The clinical significance of cytogenetic abnormalities (CA) present in randomly sampled (RS) or focal lesion (FL) bone marrow sites was examined in 419 untreated myeloma patients. Among 290 patients with gene expression profiling (GEP) data generated from RS sites, GEP-defined high-risk was present in 52% of the RS+/FL+ group but in only 9% of the remainder (P < 0·001). The RS+/FL+ constellation (18%) was an independent predictor of poor survival, also after adjusting for GEP-derived risk and TP53 status (Hazard ratio = 2·42, P = 0·004). The prevalence of high-risk myeloma in the RS+/FL+ group may reflect a dissemination-prone condition not shared by the other three groups. [source] Prediction of survival using absolute lymphocyte count for newly diagnosed patients with multiple myeloma: a retrospective studyBRITISH JOURNAL OF HAEMATOLOGY, Issue 6 2008Hilmi Ege Summary Absolute lymphocyte count (ALC) recovery after autologous stem cell transplantation for multiple myeloma (MM) has been reported to be an independent prognostic factor for clinical outcome. The role of ALC on survival in newly diagnosed untreated MM patients is unknown. Between 1994 and 2002, we analysed retrospectively 537 MM patients of 1835 consecutive MM patients that were neither uniformly treated nor part of a clinical trail, but originally diagnosed and followed at the Mayo Clinic. The primary endpoint was to assess the role of ALC at the time of MM diagnosis on overall survival (OS). The median follow-up was 35·1 months (range: 1,152·5 months). ALC, as a continuous variable, was identified as prognostic factor for OS (Hazard ratio = 0·473, 95% confidence interval = 0·359,0·618, P < 0·0001). MM patients with an ALC ,1·4 × 109/l experienced superior OS compared with MM patients with an ALC <1·4 × 109/l (65 vs. 26 months, P < 0·0001). Multivariate analysis identified ALC as an independent prognostic factor for OS. This study showed that, in newly diagnosed MM, ALC is an independent prognostic factor for OS, suggesting a significant role of host immune status in the survival of MM. [source] Topical beta-blockers and the risk of cardiovascular mortalityACTA OPHTHALMOLOGICA, Issue 2007NM JANSONIUS Purpose: Recently, the Blue Mountains Eye Study reported an association between the use of topical timolol and cardiovascular mortality (Lee et al. Ophthalmology 2006). The purpose of the present study was to confirm or falsify this clinically very important finding, using data from the population-based Rotterdam Study. Methods: 6971 participants of the Rotterdam Study, a longitudinal population based study of all residents aged 55 years and older from a district of Rotterdam, The Netherlands, were followed from 1991 onwards. Medication use and morbidity were recorded continuously during follow-up. For the current analysis, baseline use of topical beta-blockers and systemic cardiovascular medication as well as baseline cardiovascular morbidity were used, aiming to follow the design of the Blue Mountains Eye Study as close as possible. Cause of death was registered up to 1-1-2005. Data were analysed using Cox regression; Hazard ratios of topical beta-blocker use were adjusted for age, sex, cardiovascular morbidity and use of systemic cardiovascular medication. Results: Mean age at baseline was 69 years (SD 9 years); 146 participants were using topical beta-blockers at baseline. 2726 participants died during follow-up (all cause mortality 40.1%), 611 (9.0%) had a cardiovascular cause of death. Hazard ratio of topical beta-blocker use was 0.80 (95% confidence interval 0.63-1.02; P=0.07) for all cause mortality and 0.78 (0.46-1.29; P=0.32) for cardiovascular mortality. Conclusions: In our data, the use of topical beta-blockers at baseline was not associated with either all cause mortality or cardiovascular mortality during follow-up. [source] Treatment of Anemia With Darbepoetin Alfa in Heart FailureCONGESTIVE HEART FAILURE, Issue 3 2010William T. Abraham MD Anemia is common in heart failure (HF) patients. A prespecified pooled analysis of 2 randomized, double-blind, placebo-controlled studies evaluated darbepoetin alfa (DA) in 475 anemic patients with HF (hemoglobin [Hb], 9.0,12.5 g/dL). DA was administered subcutaneously every 2 weeks and titrated to achieve and maintain a target Hb level of 14.0±1.0 g/dL. By week 27, mean (SD) Hb concentrations did not increase with placebo but increased with DA from 11.5 (0.7) to 13.3 (1.3) g/dL. Hazard ratios (HRs) for DA compared with placebo for all-cause death or first HF hospitalization (composite end point), all-cause death, and HF hospitalization by month 12 were 0.67 (95% confidence interval [CI], 0.44,1.03; P=.067), 0.76 (95% CI, 0.39,1.48; P=.419), and 0.66 (95% CI, 0.40,1.07; P=.093), respectively. Incidence of adverse events was similar in both groups. In post hoc analyses, improvement in the composite end point was significantly associated with the mean Hb change from baseline (adjusted HR, 0.40; P=.017) with DA treatment. There was no increased risk of all-cause mortality or first HF hospitalization with DA in patients with reduced renal function or elevated baseline B-type natriuretic peptide, a biomarker of worse HF. These results suggest that DA is well tolerated, corrects HF-associated anemia, and may have favorable effects on clinical outcomes., Congest Heart Fail. 2010;16:87,95. © 2010 Wiley Periodicals, Inc. [source] Fruit and vegetable consumption and pancreatic cancer risk in the European Prospective Investigation into Cancer and NutritionINTERNATIONAL JOURNAL OF CANCER, Issue 8 2009Alina Vrieling Abstract Many case-control studies have suggested that higher consumption of fruit and vegetables is associated with a lower risk of pancreatic cancer, whereas cohort studies do not support such an association. We examined the associations of the consumption of fruits and vegetables and their main subgroups with pancreatic cancer risk within the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC is comprised of over 520,000 subjects recruited from 10 European countries. The present study included 555 exocrine pancreatic cancer cases after an average follow-up of 8.9 years. Estimates of risk were obtained by Cox proportional hazard models, stratified by age at recruitment, gender, and study center, and adjusted for total energy intake, weight, height, history of diabetes mellitus, and smoking status. Total consumption of fruit and vegetables, combined or separately, as well as subgroups of vegetables and fruits were unrelated to risk of pancreatic cancer. Hazard ratios (95% CI) for the highest versus the lowest quartile were 0.92 (0.68,1.25) for total fruit and vegetables combined, 0.99 (0.73,1.33) for total vegetables, and 1.02 (0.77,1.36) for total fruits. Stratification by gender or smoking status, restriction to microscopically verified cases, and exclusion of the first 2 years of follow-up did not materially change the results. These results from a large European prospective cohort suggest that higher consumption of fruit and vegetables is not associated with decreased risk of pancreatic cancer. © 2008 Wiley-Liss, Inc. [source] Time to clearance of human papillomavirus infection by type and human immunodeficiency virus serostatusINTERNATIONAL JOURNAL OF CANCER, Issue 7 2006Jill E. Koshiol Abstract Persistent infection with high-risk human papillomavirus (HPV) is central to cervical carcinogenesis. Certain high-risk types, such as HPV16, may be more persistent than other HPV types, and type-specific HPV persistence may differ by HIV serostatus. This study evaluated the association between HPV type and clearance of HPV infections in 522 HIV-seropositive and 279 HIV-seronegative participants in the HIV Epidemiology Research Study (HERS, United States, 1993,2000). Type-specific HPV infections were detected using MY09/MY11/HMB01-based PCR and 26 HPV type-specific probes. The estimated duration of type-specific infections was measured from the first HPV-positive visit to the first of two consecutive negative visits. Hazard ratios (HRs) and 95% confidence intervals (CIs) for HPV clearance were calculated using Cox models adjusted for study site and risk behavior (sexual or injection drugs). A total of 1,800 HPV infections were detected in 801 women with 4.4 years median follow-up. HRs for clearance of HPV16 and related types versus low-risk HPV types were 0.79 (95% CI: 0.64,0.97) in HIV-positive women and 0.86 (95% CI: 0.59,1.27) in HIV-negative women. HRs for HPV18 versus low-risk types were 0.80 (95% CI: 0.56,1.16) and 0.57 (95% CI: 0.22,1.45) for HIV-positive and -negative women, respectively. HPV types within the high-risk category had low estimated clearance rates relative to low-risk types, but HRs were not substantially modified by HIV serostatus. © 2006 Wiley-Liss, Inc. [source] Finite Element Analysis of the Proximal Femur and Hip Fracture Risk in Older Men,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 3 2009Eric S Orwoll Abstract Low areal BMD (aBMD) is associated with increased risk of hip fracture, but many hip fractures occur in persons without low aBMD. Finite element (FE) analysis of QCT scans provides a measure of hip strength. We studied the association of FE measures with risk of hip fracture in older men. A prospective case-cohort study of all first hip fractures (n = 40) and a random sample (n = 210) of nonfracture cases from 3549 community-dwelling men ,65 yr of age used baseline QCT scans of the hip (mean follow-up, 5.6 yr). Analyses included FE measures of strength and load-to-strength ratio and BMD by DXA. Hazard ratios (HRs) for hip fracture were estimated with proportional hazards regression. Both femoral strength (HR per SD change = 13.1; 95% CI: 3.9,43.5) and the load-to-strength ratio (HR = 4.0; 95% CI: 2.7,6.0) were strongly associated with hip fracture risk, as was aBMD as measured by DXA (HR = 5.1; 95% CI: 2.8,9.2). After adjusting for age, BMI, and study site, the associations remained significant (femoral strength HR = 6.5, 95% CI: 2.3,18.3; load-to-strength ratio HR = 4.3, 95% CI: 2.5,7.4; aBMD HR = 4.4, 95% CI: 2.1,9.1). When adjusted additionally for aBMD, the load-to-strength ratio remained significantly associated with fracture (HR = 3.1, 95% CI: 1.6,6.1). These results provide insight into hip fracture etiology and demonstrate the ability of FE-based biomechanical analysis of QCT scans to prospectively predict hip fractures in men. [source] Enhanced Predictive Power of Quantitative TWA during Routine Exercise Testing in the Finnish Cardiovascular StudyJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 4 2009MIKKO MINKKINEN B.M.S. Introduction: We examined whether quantification of T-wave alternans (TWA) enhances this parameter's capacity to evaluate the risk for total and cardiovascular mortality and sudden cardiac death (SCD). Methods and Results: The Finnish Cardiovascular Study (FINCAVAS) enrolled consecutive patients (n = 2,119; 1,342 men and 777 women) with a clinically indicated exercise test with bicycle ergometer. TWA (time domain-modified moving average method) was analyzed from precordial leads, and the results were grouped in increments of 10 ,V. Hazard ratios (HR) for total and cardiovascular mortality and SCD were estimated for preexercise, routine exercise, and postexercise stages. Cox regression analysis was performed. During follow-up of 47.1 ± 12.9 months (mean ± standard deviation [SD]), 126 patients died: 62 were cardiovascular deaths, and 33 of these deaths were sudden. During preexercise, TWA , 20 ,V predicted the risk for total and cardiovascular mortality (maximum HR >4.4 at 60 ,V, P < 0.02 for both). During exercise, HRs of total and cardiovascular mortality were significant when TWA measured ,50 ,V, with 90 ,V TWA yielding maximum HRs for total and cardiovascular death of 3.1 (P = 0.03) and 6.4 (P = 0.002), respectively. During postexercise, TWA ,60 ,V indicated risk for total and cardiovascular mortality, with maximum HR of 3.4 at 70 ,V (P = 0.01) for cardiovascular mortality. SCD was strongly predicted by TWA levels ,60 ,V during exercise, with maximum HR of 4.6 at 60 ,V (P = 0.002), but was not predicted during pre- or postexercise. Conclusion: Quantification of TWA enhances its capacity for determination of the risk for total and cardiovascular mortality and SCD in low-risk populations. Its prognostic power is superior during exercise compared to preexercise or postexercise. [source] The Paradox of Obesity in Patients with Heart FailureJOURNAL OF THE AMERICAN ACADEMY OF NURSE PRACTITIONERS, Issue 12 2005Jill A. Hall MS Purpose Heart failure (HF) patients often have comorbid conditions that confound management and adversely affect prognosis. The purpose of this study was to determine whether the obesity paradox is also present in hospitalized HF patients in an integrated healthcare system. Data sources A cohort of 2707 patients with a primary diagnosis of HF was identified within an integrated, 20-hospital healthcare system. Patients were identified by ICD-9 codes or a left ventricular ejection fraction ,40% dating back to 1995. Body mass index (BMI) was calculated using the first measured height and weight when hospitalized with HF. Survival rates were calculated using Kaplan Meier estimation. Hazard ratios for 3-year mortality with 95% confidence intervals were assessed using Cox regression, controlling for age, gender, and severity of illness at time of diagnosis. Conclusions Three-year survival rates paradoxically improved for patients with increasing BMI. Survival rates for the larger three BMI quartiles were significantly better than for the lowest quartile after adjusting for severity of illness, age, and gender. Implications for practice While obesity increases the risk of developing HF approximately twofold, reports involving stable outpatients suggest that obesity is associated with improved survival after the development of HF. This finding is paradoxical because obesity increases the risk and worsens the prognosis of other cardiovascular diseases. [source] Evaluation of the prognostic value of the risk, injury, failure, loss and end-stage renal failure (RIFLE) criteria for acute kidney injuryNEPHROLOGY, Issue 5 2008JOSE R PEREZ VALDIVIESO SUMMARY: Aim: The experts have argued about the use of the risk, injury, failure, loss and end-stage renal failure (RIFLE) criteria as a prognosis scoring system. We examined the association between in-hospital mortality and the RIFLE criteria, and discussed its accuracy as a prognosis factor. Methods: In this prospective study, we analysed the data gathered from a cohort of 956 patients admitted in a Spanish tertiary hospital between January 1998 and April 2006. Hazard ratios for mortality, and survival curves within 60 days were calculated. Discrimination and calibration of the model were also assessed. Results: Excluding 53 patients, 903 patients were finally analysed. We classified them into groups according to the maximum RIFLE class reached during their admission. The RIFLE class was assessed by the glomerular filtration rate criterion. We found an increase in the in-hospital mortality risk. Cox proportional hazard models showed that RIFLE classes risk, injury, and failure were significant predictive factors (hazard ratios were 2.77, 3.23 and 3.52, respectively; P for trend was 0.005). The multivariate analyses from the cross-classification of the participants according to Liano score values (severity of illness) and RIFLE classes showed additive effects of the exposures on in-hospital mortality. Conclusion: In this population, the risk of in-hospital mortality during the acute kidney injury (AKI) episode was positively associated with RIFLE classes. We showed that the RIFLE classification system had discriminative power in predicting hospital mortality within 60 days in AKI patients, but not better than a specific AKI predictive model. However, a combined use of both may give a more robust prognosis system. [source] A possible link between the pubertal growth of girls and breast cancer in their daughtersAMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 2 2008David J.P. Barker One hypothesis for the origins of breast cancer is that it is initiated by exposure of developing breast tissue in utero to maternal sex hormones. The sex hormone profile is established at puberty, when it regulates growth of the pelvic bones. The pubertal growth of girls is characterized by broadening and rounding of the pelvis. The maximal width between their iliac crests, the intercristal width, increases more rapidly than in boys. We hypothesized that higher sex hormone concentrations at puberty produce larger intercristal widths, and these are markers of increased breast cancer risk in the next generation. We followed up 6,370 women who were born in Helsinki during 1934,1944, and whose mothers' pelvic bones were measured during routine antenatal care. Women whose mothers had large intercristal widths had higher rates of breast cancer. In those born at or after 40 weeks gestation, the hazard ratio for breast cancer was 3.7 (95% CI: 2.1,6.6) if their mother's intercristal width was greater than 30 cm. Among women born to multiparous mothers this hazard ratio rose to 7.2 (3.4,15.4). Hazard ratios for breast cancer were also higher in the daughters of mothers with round iliac crests. Pelvic bone measurements which increase similarly in girls and boys at puberty did not predict breast cancer. We conclude that the intercristal width, and the roundness of the iliac crests, are markers of mothers' sex hormones, and postulate that high concentrations cause genetic instability in differentiating breast cells in their daughters in utero. Am. J. Hum. Biol., 2008. © 2007 Wiley-Liss, Inc. [source] Psychosocial factors and shoulder symptom development among workersAMERICAN JOURNAL OF INDUSTRIAL MEDICINE, Issue 1 2009Caroline K. Smith MPH Abstract Background Shoulder injuries are a common cause of pain and discomfort. Many work-related factors have been associated with the onset of shoulder symptoms. The psychosocial concepts in the demand,control model have been studied in association with musculoskeletal symptoms but with heterogeneous findings. The purpose of this study was to assess the relationship between the psychosocial concepts of the demand,control model and the incidence of shoulder symptoms in a working population. Methods After following 424 subjects for approximately 1 year, 85 incident cases were identified from self-reported data. Cox proportional hazards modeling was used to assess the associations between shoulder symptoms and demand,control model quadrants. Results Cases were more likely to be female and report other upper extremity symptoms at baseline (P,<,0.05). From the hazard models, being in either a passive or high strain job quadrant was associated with the incidence of shoulder symptoms. Hazard ratios were 2.17, 95% CI 1.02,4.66 and 2.19, 95% CI 1.08,4.42, respectively. Conclusions Using self-reporting to determine demand,control quadrants was successful in identifying subjects at risk of developing work-related shoulder symptoms. Research is needed to determine if this relationship holds with clinically diagnosed shoulder and other upper extremity musculoskeletal disorders. This may be part of a simple tool for assessing risk of developing these UEMSDs. Am. J. Ind. Med. 52:57,68, 2009. © 2008 Wiley-Liss, Inc. [source] T1N0 Triple Negative Breast Cancer: Risk of Recurrence and Adjuvant ChemotherapyTHE BREAST JOURNAL, Issue 5 2009Henry G. Kaplan MD Abstract:, Adjuvant treatment of T1N0 breast cancer (BC) has evolved in recent years with chemotherapy options dependent on tumor size and cellular characteristics. Our goal is to describe the difference in outcome between T1N0 triple negative (TriNeg) and estrogen/progesterone receptor positive/her2/neu-negative BC. From our institute's registry, we identified primary BC patients diagnosed from 1998 to 2005, estrogen/progesterone receptor negative (ER,/PR,)/her-2/neu negative (her2,) (TriNeg = 110) and ER+/PR+/her2, (HR+/her2, = 919). Clinical diagnosis and treatment variables were chart abstracted. Vital and disease status were updated annually. Pearson chi-squared tests were used for bivariate analysis. Hazard ratios were calculated using the Cox proportional hazards model. Average patient age was 59 years, range 23,93 years and average length of follow-up was 4.22 years. T-stage distribution for HR+/her2, patients was 9% T1a (>0.1, ,0.5 cm), 34% T1b (>0.5 cm, ,1 cm), 57% T1c (>1 cm, ,2 cm) and for TriNeg, 6% T1a, 21% T1b, and 73% T1c. Sixty-five per cent of T1b and 73% T1c TriNeg patients received chemotherapy versus 7% of T1b and 32% of T1c HR+/her2, patients with TriNeg patients more likely to receive doxorubicin/cyclophosphamide/paclitaxel combined therapy. Recurrence rates were the following, T1b: 8.7%, TriNeg (2/23) versus 0%, HR+/her2, (0/315) and T1c: 8.8%, TriNeg (7/80) versus 2.1%, HR+/her2, (11/523). Five year relapse-free survival was 98% in the HR+/her2, group and 89% in the TriNeg group (log rank test = 27.77, p < 0.001). The hazard ratio for recurrence in the TriNeg group was 6.57 (95% CI = 2.34, 18.49) adjusted for age, tumor size, and adjuvant chemotherapy. Triple negative T1N0 patients have greater recurrence risk in spite of more aggressive therapy by both number treated and adjuvant chemotherapy type even in a low-risk category. New treatment modalities specific for triple negative disease are urgently needed. [source] Use of Illicit Drugs and Erectile Dysfunction Medications and Subsequent HIV Infection among Gay Men in Sydney, AustraliaTHE JOURNAL OF SEXUAL MEDICINE, Issue 8 2009Garrett Prestage PhD ABSTRACT Introduction., Use of illicit drugs and oral erectile dysfunction medications (OEM) have been associated with risk behavior among gay men. Aim., To determine the effects of illicit drugs and OEM as risk factors for HIV seroconversion in a community-based cohort of HIV-negative homosexually active men in Sydney, Australia. Main Outcome Measures., Drug use in the previous 6 months and at the most recent sexual encounter; Most recent occasions of unprotected and protected anal intercourse; HIV-positive diagnosis. Methods., From June 2001 to June 2007, participants were followed up with 6-monthly detailed behavioral interviews and annual testing for HIV. Detailed information about sexual, drug-using and other behavior was collected. Results., Among 1,427 participants enrolled, 53 HIV seroconverters were identified by June 2007. At baseline, 62.7% reported using illicit drugs in the previous 6 months, including 10.7% who reported at least weekly use. Illicit drug use was associated with unprotected anal intercourse with casual partners (P < 0.001). Use of illicit drugs was associated with increased risk of HIV infection at a univariate level, and this risk increased with greater frequency of use. This was also true of the use of OEM. Use of each type of illicit drug was included in multivariate analysis, and after controlling for sexual risk behaviors, only use of OEM remained significantly predictive of HIV infection (Hazard ratios [HR] = 1.75, CI = 1.31,2.33, P < 0.001), although amyl nitrite was of borderline significance (HR = 1.26, CI = 0.98,1.62, P = 0.074). Conclusion., The association between drug use and increased risk of HIV infection was strongest for drugs used specifically to enhance sexual pleasure, particularly OEM. The risk of infection was substantially increased when both OEM and methamphetamine were used. Within more "adventurous" gay community subcultures, the interconnectedness of sexual behavior and drug use may be key to understanding HIV risk and is an appropriate priority in HIV-prevention efforts in this population. Prestage G, Jin F, Kippax S, Zablotska I, Imrie J, and Grulich A. Use of illicit drugs and erectile dysfunction medications and subsequent HIV infection among gay men in Sydney, Australia. J Sex Med 2009;6:2311,2320. [source] Telomere length predicts poststroke mortality, dementia, and cognitive declineANNALS OF NEUROLOGY, Issue 2 2006Carmen Martin-Ruiz PhD Objective Long-term cognitive development is variable among stroke survivors, with a high proportion developing dementia. Early identification of those at risk is highly desirable to target interventions for secondary prevention. Telomere length in peripheral blood mononuclear cells was tested as prognostic risk marker. Methods A cohort of 195 nondemented stroke survivors was followed prospectively from 3 months after stroke for 2 years for cognitive assessment and diagnosis of dementia and for 5 years for survival. Telomere lengths in peripheral blood mononuclear cells were measured at 3 months after stroke by in-gel hybridization. Hazard ratios for survival in relation to telomere length and odds ratios for dementia were estimated using multivariate techniques, and changes in Mini-Mental State Examination scores between baseline and 2 years were related to telomere length using multivariate linear regression. Results Longer telomeres at baseline were associated with reduced risk for death (hazard ratio for linear trend per 1,000bp = 0.52; 95% confidence interval, 0.28,0.98; p = 0.04, adjusted for age) and dementia (odds ratio for linear trend per 1,000bp = 0.19; 95% confidence interval, 0.07,0.54; p = 0.002) and less reduction in Mini-Mental State Examination score (p = 0.04, adjusted for baseline score). Interpretation Telomere length is a prognostic marker for poststroke cognitive decline, dementia, and death. Ann Neurol 2006 [source] Socio-economic status and survival from breast cancer for young, Australian, urban womenAUSTRALIAN AND NEW ZEALAND JOURNAL OF PUBLIC HEALTH, Issue 2 2010Katherine I. Morley Abstract Objective: To estimate the association between measures of socio-economic status (SES) and breast cancer (BC) survival for young, urban Australian women. Methods: We used a population-based sample of 1,029 women followed prospectively for a median of 7.9 years. SES was defined by education and area of residence. Hazard ratios (HRs) associated with SES measures were estimated for (i) distant recurrence (DR) and (ii) all-cause mortality as end-points. Results: HRs for area of residence were not significantly different from unity, with or without adjustment for age at diagnosis and education level. The univariable HR estimate of DR for women with university education compared with women with incomplete high school education was 1.51 (95% CI = 1.08 , 2.13, p = 0.02), which reduced to 1.20 (95% CI = 0.85 , 1.72, p = 0.3) after adjusting for age at diagnosis and area of residence. Adjusting for prognostic factors differentially distributed across SES groups did not substantially alter the association between survival and SES. Conclusions: Among young, urban Australian women there is no association between SES and BC survival. Implications: This lack of estimates of association may be partly attributed to universal access to adequate breast cancer care in urban areas. [source] |