Prognostic factors and risk groups in T1G3 non-muscle-invasive bladder cancer patients initially treated with Bacillus Calmette-Guérin: results of a retrospective multicenter study of 2451 patients

BACKGROUND The impact of prognostic factors in T1G3 non-muscle-invasive bladder cancer (BCa) patients is critical for proper treatment decision making. OBJECTIVE To assess prognostic factors in patients who received bacillus Calmette-Guérin (BCG) as initial intravesical treatment of T1G3 tumors and to identify a subgroup of high-risk patients who should be considered for more aggressive treatment. DESIGN, SETTING, AND PARTICIPANTS Individual patient data were collected for 2451 T1G3 patients from 23 centers who received BCG between 1990 and 2011. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Using Cox multivariable regression, the prognostic importance of several clinical variables was assessed for time to recurrence, progression, BCa-specific survival, and overall survival (OS). RESULTS AND LIMITATIONS With a median follow-up of 5.2 yr, 465 patients (19%) progressed, 509 (21%) underwent cystectomy, and 221 (9%) died because of BCa. In multivariable analyses, the most important prognostic factors for progression were age, tumor size, and concomitant carcinoma in situ (CIS); the most important prognostic factors for BCa-specific survival and OS were age and tumor size. Patients were divided into four risk groups for progression according to the number of adverse factors among age ≥ 70 yr, size ≥ 3 cm, and presence of CIS. Progression rates at 10 yr ranged from 17% to 52%. BCa-specific death rates at 10 yr were 32% in patients ≥ 70 yr with tumor size ≥ 3 cm and 13% otherwise. CONCLUSIONS T1G3 patients ≥ 70 yr with tumors ≥ 3 cm and concomitant CIS should be treated more aggressively because of the high risk of progression. PATIENT SUMMARY Although the majority of T1G3 patients can be safely treated with intravesical bacillus Calmette-Guérin, there is a subgroup of T1G3 patients with age ≥ 70 yr, tumor size ≥ 3 cm, and concomitant CIS who have a high risk of progression and thus require aggressive treatment.

Usefulness of electrocardiographic parameters for risk prediction in arrhythmogenic right ventricular dysplasia

The value of electrocardiographic findings predicting adverse outcome in patients with arrhythmogenic right ventricular dysplasia (ARVD) is not well known. We hypothesized that ventricular depolarization and repolarization abnormalities on the 12-lead surface electrocardiogram (ECG) predict adverse outcome in patients with ARVD. ECGs of 111 patients screened for the 2010 ARVD Task Force Criteria from 3 Swiss tertiary care centers were digitized and analyzed with a digital caliper by 2 independent observers blinded to the outcome. ECGs were compared in 2 patient groups: (1) patients with major adverse cardiovascular events (MACE: a composite of cardiac death, heart transplantation, survived sudden cardiac death, ventricular fibrillation, sustained ventricular tachycardia, or arrhythmic syncope) and (2) all remaining patients. A total of 51 patients (46%) experienced MACE during a follow-up period with median of 4.6 years (interquartile range 1.8 to 10.0). Kaplan-Meier analysis revealed reduced times to MACE for patients with repolarization abnormalities according to Task Force Criteria (p = 0.009), a precordial QRS amplitude ratio (∑QRS mV V1 to V3/∑QRS mV V1 to V6) of ≤ 0.48 (p = 0.019), and QRS fragmentation (p = 0.045). In multivariable Cox regression, a precordial QRS amplitude ratio of ≤ 0.48 (hazard ratio [HR] 2.92, 95% confidence interval [CI] 1.39 to 6.15, p = 0.005), inferior leads T-wave inversions (HR 2.44, 95% CI 1.15 to 5.18, p = 0.020), and QRS fragmentation (HR 2.65, 95% CI 1.1 to 6.34, p = 0.029) remained as independent predictors of MACE. In conclusion, in this multicenter, observational, long-term study, electrocardiographic findings were useful for risk stratification in patients with ARVD, with repolarization criteria, inferior leads TWI, a precordial QRS amplitude ratio of ≤ 0.48, and QRS fragmentation constituting valuable variables to predict adverse outcome.

Low back pain risk factors associated with persistence, recurrence and delayed presentation

BACKGROUND: There is little knowledge in the literature on the role of time-related variables for the prognosis of acute and subacute low back pain (LBP). OBJECTIVE: The aim of this study was to estimate the relationship between time-related LBP characteristics and prognostic factors for acute/subacute LBP. METHODS: We performed a prospective inception cohort study of 315 patients attending a health practitioner for acute/subacute LBP or recurrent LBP. One-tailed correlations were conducted between patient characteristics and time-related variables. RESULTS: The pattern of correlation between risk factors for and resources against persistent LBP differed between three time-related variables. 'Subacute LBP' and 'delayed presentation' were positively associated with psychological factors. Both indicators were negatively correlated with resources against development of persistent LBP. Moreover, 'delayed presentation' was related positively with occupational stressors. In contrast, 'recurrent LBP' was only related to more impaired health-related factors. CONCLUSIONS: Patients with current LBP waiting longer until seeking help in primary care have a more disadvantageous profile of occupational and psychological risk factors and lower resource levels. A similar but less pronounced pattern occurred in those with subacute LBP compared to those with acute LBP. Consideration of time characteristics of LBP may help to better understand LBP.

Association between trends in clinical variables and outcome in intensive care patients with faecal peritonitis: analysis of the GenOSept cohort.

INTRODUCTION Patients admitted to intensive care following surgery for faecal peritonitis present particular challenges in terms of clinical management and risk assessment. Collaborating surgical and intensive care teams need shared perspectives on prognosis. We aimed to determine the relationship between dynamic assessment of trends in selected variables and outcomes. METHODS We analysed trends in physiological and laboratory variables during the first week of intensive care unit (ICU) stay in 977 patients at 102 centres across 16 European countries. The primary outcome was 6-month mortality. Secondary endpoints were ICU, hospital and 28-day mortality. For each trend, Cox proportional hazards (PH) regression analyses, adjusted for age and sex, were performed for each endpoint. RESULTS Trends over the first 7 days of the ICU stay independently associated with 6-month mortality were worsening thrombocytopaenia (mortality: hazard ratio (HR) = 1.02; 95% confidence interval (CI), 1.01 to 1.03; P <0.001) and renal function (total daily urine output: HR =1.02; 95% CI, 1.01 to 1.03; P <0.001; Sequential Organ Failure Assessment (SOFA) renal subscore: HR = 0.87; 95% CI, 0.75 to 0.99; P = 0.047), maximum bilirubin level (HR = 0.99; 95% CI, 0.99 to 0.99; P = 0.02) and Glasgow Coma Scale (GCS) SOFA subscore (HR = 0.81; 95% CI, 0.68 to 0.98; P = 0.028). Changes in renal function (total daily urine output and renal component of the SOFA score), GCS component of the SOFA score, total SOFA score and worsening thrombocytopaenia were also independently associated with secondary outcomes (ICU, hospital and 28-day mortality). We detected the same pattern when we analysed trends on days 2, 3 and 5. Dynamic trends in all other measured laboratory and physiological variables, and in radiological findings, changes inrespiratory support, renal replacement therapy and inotrope and/or vasopressor requirements failed to be retained as independently associated with outcome in multivariate analysis. CONCLUSIONS Only deterioration in renal function, thrombocytopaenia and SOFA score over the first 2, 3, 5 and 7 days of the ICU stay were consistently associated with mortality at all endpoints. These findings may help to inform clinical decision making in patients with this common cause of critical illness.

Modelling the system behaviour of wet snow avalanches using an expert system approach for risk management on high alpine traffic roads

The presented approach describes a model for a rule-based expert system calculating the temporal variability of the release of wet snow avalanches, using the assumption of avalanche triggering without the loading of new snow. The knowledge base of the model is created by using investigations on the system behaviour of wet snow avalanches in the Italian Ortles Alps, and is represented by a fuzzy logic rule-base. Input parameters of the expert system are numerical and linguistic variables, measurable meteorological and topographical factors and observable characteristics of the snow cover. Output of the inference method is the quantified release disposition for wet snow avalanches. Combining topographical parameters and the spatial interpolation of the calculated release disposition a hazard index map is dynamically generated. Furthermore, the spatial and temporal variability of damage potential on roads exposed to wet snow avalanches can be quantified, expressed by the number of persons at risk. The application of the rule base to the available data in the study area generated plausible results. The study demonstrates the potential for the application of expert systems and fuzzy logic in the field of natural hazard monitoring and risk management.

Validity of SYNTAX score II for risk stratification of percutaneous coronary interventions: A patient-level pooled analysis of 5,433 patients enrolled in contemporary coronary stent trials.

OBJECTIVES To assess the clinical profile and long-term mortality in SYNTAX score II based strata of patients who received percutaneous coronary interventions (PCI) in contemporary randomized trials. BACKGROUND The SYNTAX score II was developed in the randomized, all-comers' SYNTAX trial population and is composed by 2 anatomical and 6 clinical variables. The interaction of these variables with the treatment provides individual long-term mortality predictions if a patient undergoes coronary artery bypass grafting (CABG) or PCI. METHODS Patient-level (n=5433) data from 7 contemporary coronary drug-eluting stent (DES) trials were pooled. The mortality for CABG or PCI was estimated for every patient. The difference in mortality estimates for these two revascularization strategies was used to divide the patients into three groups of theoretical treatment recommendations: PCI, CABG or PCI/CABG (the latter means equipoise between CABG and PCI for long term mortality). RESULTS The three groups had marked differences in their baseline characteristics. According to the predicted risk differences, 5115 patients could be treated either by PCI or CABG, 271 should be treated only by PCI and, rarely, CABG (n=47) was recommended. At 3-year follow-up, according to the SYNTAX score II recommendations, patients recommended for CABG had higher mortality compared to the PCI and PCI/CABG groups (17.4%; 6.1% and 5.3%, respectively; P<0.01). CONCLUSIONS The SYNTAX score II demonstrated capability to help in stratifying PCI procedures.

Low serum testosterone and increased diastolic ocular perfusion pressure: a risk for retinal microvasculature

BACKGROUND Low levels of testosterone in men and changes in retinal microvascular calibre are both associated with hypertension and cardiovascular disease risk. Sex hormones are also associated with blood flow in microvascular beds which might be a key intermediate mechanism in the development of hypertension. Whether a direct association between endogenous testosterone and retinal microvascular calibre exists is currently unknown. We aimed to determine whether testosterone is independently associated with ocular perfusion via a possible association with retinal vascular calibre or whether it plays only a secondary role via its effect on blood pressure in a bi-ethnic male cohort. PROBANDS AND METHODS A total of 72 black and 81 white men (28-68 years of age) from the follow-up phase of the Sympathetic activity and Ambulatory Blood Pressure in Africans (SABPA) study were included in this sub-study. Ambulatory pulse pressure and intraocular perfusion pressures were obtained, while metabolic variables and testosterone were measured from fasting venous blood samples. Retinal vascular calibre was quantified from digital photographs using standardised protocols. RESULTS The black men revealed a poorer cardiometabolic profile and higher pulsatile pressure (>50 mm Hg), intraocular pressure and diastolic ocular perfusion pressure than the white men (p≤0.05). Only in the white men was free testosterone positively associated with retinal calibre, i.e. arterio-venular ratio and central retinal arterial calibre and inversely with central retinal venular calibre. These associations were not found in the black men, independent of whether pulse pressure and ocular perfusion pressure were part of the model. CONCLUSIONS These results suggest an independent, protective effect of testosterone on the retinal vasculature where an apparent vasodilatory response in the retinal resistance microvessels was observed in white men.

Associations Between Cardiovascular Risk Factors, Inflammation, and Progression of Carotid Atherosclerosis Among Smokers

INTRODUCTION The high risk of cardiovascular events in smokers requires adequate control of other cardiovascular risk factors (CVRFs) to curtail atherosclerosis progression. However, it is unclear which CVRFs have the most influence on atherosclerosis progression in smokers. METHODS In 260 smokers aged 40-70 included in a smoking cessation trial, we analyzed the association between traditional CVRFs, high-sensitivity C-reactive protein (hs-CRP), smoking cessation and 3-year progression of carotid intima-media thickness (CIMT, assessed by repeated ultrasound measurements) in a longitudinal multivariate model. RESULTS Participants (mean age 52 years, 47% women) had a mean smoking duration of 32 years with a median daily consumption of 20 cigarettes. Baseline CIMT was 1185 μm (95% confidence interval [CI]: 1082-1287) and increased by 93 μm (95% CI: 25-161) and 108 μm (95% CI: 33-183) after 1 and 3 years, respectively. Age, male sex, daily cigarette consumption, systolic blood pressure (SBP), but neither low-density lipoprotein cholesterol nor hs-CRP, were independently associated with baseline CIMT (all P ≤ .05). Baseline SBP, but neither low-density lipoprotein cholesterol nor hs-CRP, was associated with 3-year atherosclerosis progression (P = .01 at 3 years). The higher the SBP at baseline, the steeper was the CIMT increase over 3-year follow-up. We found an increase of 26 μm per each 10-mmHg raise in SBP at 1 year and an increase of 39 μm per each 10 mmHg raise in SBP at 3 years. Due to insufficient statistical power, we could not exclude an effect of smoking abstinence on CIMT progression. CONCLUSION Control of blood pressure may be an important factor to limit atherosclerosis progression in smokers, besides support for smoking cessation. IMPLICATIONS Among 260 smokers aged 40-70 years with a mean smoking duration of 32 years, baseline SBP was associated with atherosclerosis progression over 3 years, as measured by CIMT (P = .01 at 3 years), independently of smoking variables and other CVRFs. The higher the SBP at baseline, the steeper was the CIMT increase over 3-year follow-up. Our findings emphasize the importance of focusing not only on smoking cessation among smokers, but to simultaneously control other CVRFs, particularly blood pressure, in order to prevent future cardiovascular disease.

Risk Factors for Intracranial Haemorrhage in Accidents Associated with the Shower or Bathtub

BACKGROUND There has been little research on bathroom accidents. It is unknown whether the shower or bathtub are connected with special dangers in different age groups or whether there are specific risk factors for adverse outcomes. METHODS This cross-sectional analysis included all direct admissions to the Emergency Department at the Inselspital Bern, Switzerland from 1 January 2000 to 28 February 2014 after accidents associated with the bathtub or shower. Time, age, location, mechanism and diagnosis were assessed and special risk factors were examined. Patient groups with and without intracranial bleeding were compared with the Mann-Whitney U test.The association of risk factors with intracranial bleeding was investigated using univariate analysis with Fisher's exact test or logistic regression. The effects of different variables on cerebral bleeding were analysed by multivariate logistic regression. RESULTS Two hundred and eighty (280) patients with accidents associated with the bathtub or shower were included in our study. Two hundred and thirty-five (235) patients suffered direct trauma by hitting an object (83.9%) and traumatic brain injury (TBI) was detected in 28 patients (10%). Eight (8) of the 27 patients with mild traumatic brain injuries (GCS 13-15), (29.6%) exhibited intracranial haemorrhage. All patients with intracranial haemorrhage were older than 48 years and needed in-hospital treatment. Patients with intracranial haemorrhage were significantly older and had higher haemoglobin levels than the control group with TBI but without intracranial bleeding (p<0.05 for both).In univariate analysis, we found that intracranial haemorrhage in patients with TBI was associated with direct trauma in general and with age (both p<0.05), but not with the mechanism of the fall, its location (shower or bathtub) or the gender of the patient. Multivariate logistic regression analysis identified only age as a risk factor for cerebral bleeding (p<0.05; OR 1.09 (CI 1.01;1.171)). CONCLUSION In patients with ED admissions associated with the bathtub or shower direct trauma and age are risk factors for intracranial haemorrhage. Additional effort in prevention should be considered, especially in the elderly.