872 resultados para Patient based-outcomes


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BACKGROUND Patients with prior coronary artery bypass graft surgery (CABG) who present with an acute coronary syndrome have a high risk for recurrent events. Whether intensive antiplatelet therapy with ticagrelor might be beneficial compared with clopidogrel is unknown. In this substudy of the PLATO trial, we studied the effects of randomized treatment dependent on history of CABG. METHODS Patients participating in PLATO were classified according to whether they had undergone prior CABG. The trial's primary and secondary end points were compared using Cox proportional hazards regression. RESULTS Of the 18,613 study patients, 1,133 (6.1%) had prior CABG. Prior-CABG patients had more high-risk characteristics at study entry and a 2-fold increase in clinical events during follow-up, but less major bleeding. The primary end point (composite of cardiovascular death, myocardial infarction, and stroke) was reduced to a similar extent by ticagrelor among patients with (19.6% vs 21.4%; adjusted hazard ratio [HR], 0.91 [0.67, 1.24]) and without (9.2% vs 11.0%; adjusted HR, 0.86 [0.77, 0.96]; P(interaction) = .73) prior CABG. Major bleeding was similar with ticagrelor versus clopidogrel among patients with (8.1% vs 8.7%; adjusted HR, 0.89 [0.55, 1.47]) and without (11.8% vs 11.4%; HR, 1.08 [0.98, 1.20]; P(interaction) = .46) prior CABG. CONCLUSIONS Prior-CABG patients presenting with acute coronary syndrome are a high-risk cohort for death and recurrent cardiovascular events but have a lower risk for major bleeding. Similar to the results in no-prior-CABG patients, ticagrelor was associated with a reduction in ischemic events without an increase in major bleeding.

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BACKGROUND: Patients undergoing laparoscopic Roux-en-Y gastric bypass (LRYGB) often have substantial comorbidities, which must be taken into account to appropriately assess expected postoperative outcomes. The Charlson/Deyo and Elixhauser indices are widely used comorbidity measures, both of which also have revised algorithms based on enhanced ICD-9-CM coding. It is currently unclear which of the existing comorbidity measures best predicts early postoperative outcomes following LRYGB. METHODS: Using the Nationwide Inpatient Sample, patients 18 years or older undergoing LRYGB for obesity between 2001 and 2008 were identified. Comorbidities were assessed according to the original and enhanced Charlson/Deyo and Elixhauser indices. Using multivariate logistic regression, the following early postoperative outcomes were assessed: overall postoperative complications, length of hospital stay, and conversion to open surgery. Model performance for the four comorbidity indices was assessed and compared using C-statistics and the Akaike's information criterion (AIC). RESULTS: A total of 70,287 patients were included. Mean age was 43.1 years (SD, 10.8), 81.6 % were female and 60.3 % were White. Both the original and enhanced Elixhauser indices modestly outperformed the Charlson/Deyo in predicting the surgical outcomes. All four models had similar C-statistics, but the original Elixhauser index was associated with the smallest AIC for all of the surgical outcomes. CONCLUSIONS: The original Elixhauser index is the best predictor of early postoperative outcomes in our cohort of patients undergoing LRYGB. However, differences between the Charlson/Deyo and Elixhauser indices are modest, and each of these indices provides clinically relevant insight for predicting early postoperative outcomes in this high-risk patient population.

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OBJECTIVE To assess the efficacy and safety of tocilizumab (TCZ) plus methotrexate/placebo (MTX/PBO) over 2 years and the course of disease activity in patients who discontinued TCZ due to sustained remission. METHODS ACT-RAY was a double-blind 3-year trial. Patients with active rheumatoid arthritis despite MTX were randomised to add TCZ to ongoing MTX (add-on strategy) or switch to TCZ plus PBO (switch strategy). Using a treat-to-target approach, open-label conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), other than MTX, were added from week 24 if Disease Activity Score in 28 joints based on erythrocyte sedimentation rate (DAS28-ESR) >3.2. Between weeks 52 and 104, patients in sustained clinical remission (DAS28-ESR <2.6 at two consecutive visits 12 weeks apart) discontinued TCZ and were assessed every 4 weeks for 1 year. If sustained remission was maintained, added csDMARDs, then MTX/PBO, were discontinued. RESULTS Of the 556 randomised patients, 76% completed year 2. Of patients entering year 2, 50.4% discontinued TCZ after achieving sustained remission and 5.9% achieved drug-free remission. Most patients who discontinued TCZ (84.0%) had a subsequent flare, but responded well to TCZ reintroduction. Despite many patients temporarily stopping TCZ, radiographic progression was minimal, with differences favouring add-on treatment. Rates of serious adverse events and serious infections per 100 patient-years were 12.2 and 4.4 in add-on and 15.0 and 3.7 in switch patients. In patients with normal baseline values, alanine aminotransferase elevations >3×upper limit of normal were more frequent in add-on (14.3%) versus switch patients (5.4%). CONCLUSIONS Treat-to-target strategies could be successfully implemented with TCZ to achieve sustained remission, after which TCZ was stopped. Biologic-free remission was maintained for about 3 months, but most patients eventually flared. TCZ restart led to rapid improvement. TRIAL REGISTRATION NUMBER NCT00810199.

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Introduction: Mindfulness based cognitive therapy for depression (MBCT) has shown to be effective for the reduction of depressive relapse. However, additional information regarding baseline patient characteristics and process features related to positive response could be helpful both for the provision of MBCT in clinical practice, as well as for its further development. Method: Baseline characteristics, process data, and immediate outcome (symptom change, change in attitudes and trait mindfulness) of 108 patients receiving MBCT in routine care were recorded. A newly developed self-report measure (Daily Mindfulness Scale, DMS) was applied daily during the MBCT program. Additionally, patients filed daily reports on their mindfulness practice. There was no control group available. Results: Patients with more severe initial symptoms indicated greater amounts of symptom improvement, but did not show great rates of dropout from the MBCT intervention. Younger age was related to higher rates of dropout. Contradictory to some previous data, patients with lower levels of initial trait mindfulness showed greater improvement in symptoms, even after controlling for initial levels of symptoms. Adherence to daily mindfulness practice was high. Consistent with this result, the duration of daily mindfulness practice was not related to immediate outcome. Process studies using multivariate time series analysis revealed a specific role of daily mindfulness in reducing subsequent negative mood. Conclusions: Within the range of patient present in this study and the given study design, results support the use of MBCT in more heterogeneous groups. This demanding intervention was well tolerated by patients with higher levels of symptoms, and resulted in significant improvements regarding residual symptoms. Process-outcome analyses of initial trait mindfulness and daily mindfulness both support the crucial role of changes in mindfulness for the effects of MBCT.

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Background: There is limited evidence about the impact of treatment for subclinical hypothyroidism, especially among older people. Aim: To investigate the variation in GP treatment strategies for older patients with subclinical hypothyroidism depending on country and patient characteristics. Design and setting: Case-based survey of GPs in the Netherlands, Germany, England, Ireland, Switzerland, and New Zealand. Method: The treatment strategy of GPs (treatment yes/no, starting-dose thyroxine) was assessed for eight cases presenting a woman with subclinical hypothyroidism. The cases differed in the patient characteristics of age (70 versus 85 years), vitality status (vital versus vulnerable), and thyroid-stimulating hormone (TSH) concentration (6 versus 15 mU/L). Results: A total of 526 GPs participated (the Netherlands n = 129, Germany n = 61, England n = 22, Ireland n = 21, Switzerland n = 262, New Zealand n = 31; overall response 19%). Across countries, differences in treatment strategy were observed. GPs from the Netherlands (mean treatment percentage 34%), England (40%), and New Zealand (39%) were less inclined to start treatment than GPs in Germany (73%), Ireland (62%), and Switzerland (52%) (P = 0.05). Overall, GPs were less inclined to start treatment in 85-year-old than in 70-year-old females (pooled odds ratio [OR] 0.74 [95% confidence interval [CI] = 0.63 to 0.87]). Females with a TSH of 15 mU/L were more likely to get treated than those with a TSH of 6 mU/L (pooled OR 9.49 [95% CI = 5.81 to 15.5]). Conclusion: GP treatment strategies of older people with subclinical hypothyroidism vary largely by country and patient characteristics. This variation underlines the need for a new generation of international guidelines based on the outcomes of randomised clinical trials set within primary care

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BACKGROUND Extensive coronary artery disease (CAD) is associated with higher risk. In this substudy of the PLATO trial, we examined the effects of randomized treatment on outcome events and safety in relation to the extent of CAD. METHODS Patients were classified according to presence of extensive CAD (defined as 3-vessel disease, left main disease, or prior coronary artery bypass graft surgery). The trial's primary and secondary end points were compared using Cox proportional hazards regression. RESULTS Among 15,388 study patients for whom the extent of CAD was known, 4,646 (30%) had extensive CAD. Patients with extensive CAD had more high-risk characteristics and experienced more clinical events during follow-up. They were less likely to undergo percutaneous coronary intervention (58% vs 79%, P < .001) but more likely to undergo coronary artery bypass graft surgery (16% vs 2%, P < .001). Ticagrelor, compared with clopidogrel, reduced the composite of cardiovascular death, myocardial infarction, and stroke in patients with extensive CAD (14.9% vs 17.6%, hazard ratio [HR] 0.85 [0.73-0.98]) similar to its reduction in those without extensive CAD (6.8% vs 8.0%, HR 0.85 [0.74-0.98], Pinteraction = .99). Major bleeding was similar with ticagrelor vs clopidogrel among patients with (25.7% vs 25.5%, HR 1.02 [0.90-1.15]) and without (7.3% vs 6.4%, HR 1.14 [0.98-1.33], Pinteraction = .24) extensive CAD. CONCLUSIONS Patients with extensive CAD have higher rates of recurrent cardiovascular events and bleeding. Ticagrelor reduced ischemic events to a similar extent both in patients with and without extensive CAD, with bleeding rates similar to clopidogrel.

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BACKGROUND The population-based effectiveness of thoracic endovascular aortic repair (TEVAR) versus open surgery for descending thoracic aortic aneurysm remains in doubt. METHODS Patients aged over 50 years, without a history of aortic dissection, undergoing repair of a thoracic aortic aneurysm between 2006 and 2011 were assessed using mortality-linked individual patient data from Hospital Episode Statistics (England). The principal outcomes were 30-day operative mortality, long-term survival (5 years) and aortic-related reinterventions. TEVAR and open repair were compared using crude and multivariable models that adjusted for age and sex. RESULTS Overall, 759 patients underwent thoracic aortic aneurysm repair, mainly for intact aneurysms (618, 81·4 per cent). Median ages of TEVAR and open cohorts were 73 and 71 years respectively (P < 0·001), with more men undergoing TEVAR (P = 0·004). For intact aneurysms, the operative mortality rate was similar for TEVAR and open repair (6·5 versus 7·6 per cent; odds ratio 0·79, 95 per cent confidence interval (c.i.) 0·41 to 1·49), but the 5-year survival rate was significantly worse after TEVAR (54·2 versus 65·6 per cent; adjusted hazard ratio 1·45, 95 per cent c.i. 1·08 to 1·94). After 5 years, aortic-related mortality was similar in the two groups, but cardiopulmonary mortality was higher after TEVAR. TEVAR was associated with more aortic-related reinterventions (23·1 versus 14·3 per cent; adjusted HR 1·70, 95 per cent c.i. 1·11 to 2·60). There were 141 procedures for ruptured thoracic aneurysm (97 TEVAR, 44 open), with TEVAR showing no significant advantage in terms of operative mortality. CONCLUSION In England, operative mortality for degenerative descending thoracic aneurysm was similar after either TEVAR or open repair. Patients who had TEVAR appeared to have a higher reintervention rate and worse long-term survival, possibly owing to cardiopulmonary morbidity and other selection bias.

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BACKGROUND The optimal crystalloid solution to use perioperatively in patients undergoing open radical cystectomy remains unclear. Many of the fluids used for intravenous hydration contain supraphysiologic concentrations of chloride, which can induce hyperchloremia and metabolic acidosis, resulting in renal vasoconstriction and decreased renal function. In addition, patients receiving less fluid and less sodium show faster recovery of gastrointestinal (GI) function after colonic surgery. METHODS AND DESIGN This is an investigator-initiated, single-center, randomized, controlled, parallel group trial with assessor-blinded outcome assessment, in the Department of Urology, University Hospital Bern, Switzerland. The study will involve 44 patients with bladder cancer scheduled for radical cystectomy and urinary diversion. The primary outcome is the duration between the end of surgery and the return of the GI function (first defecation). Secondary outcomes are fluid balance (body weight difference postoperatively versus preoperatively) and the incidence of kidney function disorders according to the Risk-Injury-Failure-Loss-End Stage Renal Disease (RIFLE classification). An equal number of patients are allocated to receive Ringerfundin® solution or a glucose/potassium-based balanced crystalloid solution as baseline infusion during the entire time that intravenous administration of fluid is necessary during the perioperative period. The randomized crystalloid solution is infused at a rate of 1 ml/kg/h until the bladder has been removed, followed by 3 ml/kg/h until the end of surgery. Postoperative hydration is identical in both groups and consists of 1,500 ml of the randomized crystalloid solution per 24 hours. Postoperative patient care is identical in both groups; patients are allowed to drink clear fluids immediately after surgery, and liquid diet is started on postoperative day 1, as well as active mobilization and the use of chewing gum. Body weight is measured daily in the morning. Time of first flatus and first defecation are recorded. DISCUSSION This trial assesses the benefits and harms of two different balanced crystalloid solutions for perioperative fluid management in patients undergoing open radical cystectomy with urinary diversion, with regard to return of GI function and effects on postoperative renal function. TRIAL REGISTRATION Current Controlled Trials ISRCTN32976792 (registered on November 21 2013).

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INTRODUCTION Optimal identification of subtle cognitive impairment in the primary care setting requires a very brief tool combining (a) patients' subjective impairments, (b) cognitive testing, and (c) information from informants. The present study developed a new, very quick and easily administered case-finding tool combining these assessments ('BrainCheck') and tested the feasibility and validity of this instrument in two independent studies. METHODS We developed a case-finding tool comprised of patient-directed (a) questions about memory and depression and (b) clock drawing, and (c) the informant-directed 7-item version of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Feasibility study: 52 general practitioners rated the feasibility and acceptance of the patient-directed tool. Validation study: An independent group of 288 Memory Clinic patients (mean ± SD age = 76.6 ± 7.9, education = 12.0 ± 2.6; 53.8% female) with diagnoses of mild cognitive impairment (n = 80), probable Alzheimer's disease (n = 185), or major depression (n = 23) and 126 demographically matched, cognitively healthy volunteer participants (age = 75.2 ± 8.8, education = 12.5 ± 2.7; 40% female) partook. All patient and healthy control participants were administered the patient-directed tool, and informants of 113 patient and 70 healthy control participants completed the very short IQCODE. RESULTS Feasibility study: General practitioners rated the patient-directed tool as highly feasible and acceptable. Validation study: A Classification and Regression Tree analysis generated an algorithm to categorize patient-directed data which resulted in a correct classification rate (CCR) of 81.2% (sensitivity = 83.0%, specificity = 79.4%). Critically, the CCR of the combined patient- and informant-directed instruments (BrainCheck) reached nearly 90% (that is 89.4%; sensitivity = 97.4%, specificity = 81.6%). CONCLUSION A new and very brief instrument for general practitioners, 'BrainCheck', combined three sources of information deemed critical for effective case-finding (that is, patients' subject impairments, cognitive testing, informant information) and resulted in a nearly 90% CCR. Thus, it provides a very efficient and valid tool to aid general practitioners in deciding whether patients with suspected cognitive impairments should be further evaluated or not ('watchful waiting').

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OBJECTIVE: To develop a behavioural observation method to simultaneously assess distractors and communication/teamwork during surgical procedures through direct, on-site observations; to establish the reliability of the method for long (>3 h) procedures. METHODS: Observational categories for an event-based coding system were developed based on expert interviews, observations and a literature review. Using Cohen's κ and the intraclass correlation coefficient, interobserver agreement was assessed for 29 procedures. Agreement was calculated for the entire surgery, and for the 1st hour. In addition, interobserver agreement was assessed between two tired observers and between a tired and a non-tired observer after 3 h of surgery. RESULTS: The observational system has five codes for distractors (door openings, noise distractors, technical distractors, side conversations and interruptions), eight codes for communication/teamwork (case-relevant communication, teaching, leadership, problem solving, case-irrelevant communication, laughter, tension and communication with external visitors) and five contextual codes (incision, last stitch, personnel changes in the sterile team, location changes around the table and incidents). Based on 5-min intervals, Cohen's κ was good to excellent for distractors (0.74-0.98) and for communication/teamwork (0.70-1). Based on frequency counts, intraclass correlation coefficient was excellent for distractors (0.86-0.99) and good to excellent for communication/teamwork (0.45-0.99). After 3 h of surgery, Cohen's κ was 0.78-0.93 for distractors, and 0.79-1 for communication/teamwork. DISCUSSION: The observational method developed allows a single observer to simultaneously assess distractors and communication/teamwork. Even for long procedures, high interobserver agreement can be achieved. Data collected with this method allow for investigating separate or combined effects of distractions and communication/teamwork on surgical performance and patient outcomes.

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OBJECTIVES Many paediatric antiretroviral therapy (ART) programmes in Southern Africa rely on CD4⁺ to monitor ART. We assessed the benefit of replacing CD4⁺ by viral load monitoring. DESIGN A mathematical modelling study. METHODS A simulation model of HIV progression over 5 years in children on ART, parameterized by data from seven South African cohorts. We simulated treatment programmes with 6-monthly CD4⁺ or 6- or 12-monthly viral load monitoring. We compared mortality, second-line ART use, immunological failure and time spent on failing ART. In further analyses, we varied the rate of virological failure, and assumed that the rate is higher with CD4⁺ than with viral load monitoring. RESULTS About 7% of children were predicted to die within 5 years, independent of the monitoring strategy. Compared with CD4⁺ monitoring, 12-monthly viral load monitoring reduced the 5-year risk of immunological failure from 1.6 to 1.0% and the mean time spent on failing ART from 6.6 to 3.6 months; 1% of children with CD4⁺ compared with 12% with viral load monitoring switched to second-line ART. Differences became larger when assuming higher rates of virological failure. When assuming higher virological failure rates with CD4⁺ than with viral load monitoring, up to 4.2% of children with CD4⁺ compared with 1.5% with viral load monitoring experienced immunological failure; the mean time spent on failing ART was 27.3 months with CD4⁺ monitoring and 6.0 months with viral load monitoring. Conclusion: Viral load monitoring did not affect 5-year mortality, but reduced time on failing ART, improved immunological response and increased switching to second-line ART.

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Carotid atherosclerotic disease is highly related to cerebrovascular events. Carotid endarterectomy is the common operation method to treat this disease. In this study, hemodynamics analyses are performed on the carotid arteries in three patients, whose right carotid artery had been treated by carotid endarterectomy and the left carotid artery remained untreated. Flow and loading conditions are compared between these treated and untreated carotid arteries and evaluation of the operative results is discussed. Patient-specific models are reconstructed from MDCT data. Intraoperative ultrasound flow measurements are performed on the treated carotid arteries and the obtained data are used as the boundary conditions of the models and the validations of the computational results. Finite volume method is employed to solve the transport equations and the flow and loading conditions of the models are reported. The results indicate that: (i) in two of the three patients, the internal-to-external flow rate ratio in the untreated carotid artery is larger than that in the treated one, and the average overall flow split ratio by summing up the data of both the left and right carotid arteries is about 2.15; (ii) in the carotid bulb, high wall shear stress occurs at the bifurcation near the external carotid artery in all of the cases without hard plaques; (iii) the operated arteries present low time-averaged wall shear stress at the carotid bulb, especially for the treated arteries with patch technique, indicating the possibility of the recurrence of stenosis; (iv) high temporal gradient of wall shear stress (>35 Pa/s) is shown in the narrowing regions along the vessels; and (v) in the carotid arteries without serious stenosis, the maximum velocity magnitude during mid-diastole is 32~37% of that at systolic peak, however, in the carotid artery with 50% stenosis by hard plaques, this value is nearly doubled (64%). The computational work quantifies flow and loading distributions in the treated and untreated carotid arteries of the same patient, contributing to evaluation of the operative results and indicating the recurrent sites of potential atheromatous plaques.

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BACKGROUND Diabetes mellitus and angiographic coronary artery disease complexity are intertwined and unfavorably affect prognosis after percutaneous coronary interventions, but their relative impact on long-term outcomes after percutaneous coronary intervention with drug-eluting stents remains controversial. This study determined drug-eluting stents outcomes in relation to diabetic status and coronary artery disease complexity as assessed by the Synergy Between PCI With Taxus and Cardiac Surgery (SYNTAX) score. METHODS AND RESULTS In a patient-level pooled analysis from 4 all-comers trials, 6081 patients were stratified according to diabetic status and according to the median SYNTAX score ≤11 or >11. The primary end point was major adverse cardiac events, a composite of cardiac death, myocardial infarction, and clinically indicated target lesion revascularization within 2 years. Diabetes mellitus was present in 1310 patients (22%), and new-generation drug-eluting stents were used in 4554 patients (75%). Major adverse cardiac events occurred in 173 diabetics (14.5%) and 436 nondiabetic patients (9.9%; P<0.001). In adjusted Cox regression analyses, SYNTAX score and diabetes mellitus were both associated with the primary end point (P<0.001 and P=0.028, respectively; P for interaction, 0.07). In multivariable analyses, diabetic versus nondiabetic patients had higher risks of major adverse cardiac events (hazard ratio, 1.25; 95% confidence interval, 1.03-1.53; P=0.026) and target lesion revascularization (hazard ratio, 1.54; 95% confidence interval, 1.18-2.01; P=0.002) but similar risks of cardiac death (hazard ratio, 1.41; 95% confidence interval, 0.96-2.07; P=0.08) and myocardial infarction (hazard ratio, 0.89; 95% confidence interval, 0.64-1.22; P=0.45), without significant interaction with SYNTAX score ≤11 or >11 for any of the end points. CONCLUSIONS In this population treated with predominantly new-generation drug-eluting stents, diabetic patients were at increased risk for repeat target-lesion revascularization consistently across the spectrum of disease complexity. The SYNTAX score was an independent predictor of 2-year outcomes but did not modify the respective effect of diabetes mellitus. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00297661, NCT00389220, NCT00617084, and NCT01443104.

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Objective: In the past decade, variation in outcomes between therapists (i.e., therapist effects) have become increasingly recognized as an important factor in psychotherapy. Less is known, however, about what accounts for differences between therapists. The present study investigates the possibility that therapists' basic therapy-related interpersonal skills may impact outcomes. Method: To examine this, psychotherapy postgraduate trainees completed both an observer- and an expert-rated behavioral assessment: the Therapy-Related Interpersonal Behaviors (TRIB). TRIB scores were used to predict trainees' outcomes over the course of the subsequent five years. Results: Results indicate that trainees' with more positively rated interpersonal behaviors assessed in the observer-rated group format but not in a single expert-rated format showed superior outcomes over the five-year period. This effect remained controlling for therapist characteristics (therapist gender, theoretical orientation [cognitive behavioral or psychodynamic], amount of supervision, patient's order within therapist's caseload), and patient characteristics (patient age, gender, number of comorbid diagnoses, global severity, and personality disorder diagnosis). Conclusions: These findings underscore the importance of therapists' interpersonal skills as a predictor of outcome and source of therapist effects. The potential utility of assessing therapists' and therapists-in-training interpersonal skills are discussed.

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Localized prostate cancer (PCa) is a clinically heterogeneous disease, which presents with variability in patient outcomes within the same risk stratification (low, intermediate or high) and even within the same Gleason scores. Genomic tools have been developed with the purpose of stratifying patients affected by this disease to help physicians personalize therapies and follow-up schemes. This review focuses on these tissue-based tools. At present, four genomic tools are commercially available: Decipher™, Oncotype DX®, Prolaris® and ProMark®. Decipher™ is a tool based on 22 genes and evaluates the risk of adverse outcomes (metastasis) after radical prostatectomy (RP). Oncotype DX® is based on 17 genes and focuses on the ability to predict outcomes (adverse pathology) in very low-low and low-intermediate PCa patients, while Prolaris® is built on a panel of 46 genes and is validated to evaluate outcomes for patients at low risk as well as patients who are affected by high risk PCa and post-RP. Finally, ProMark® is based on a multiplexed proteomics assay and predicts PCa aggressiveness in patients found with similar features to Oncotype DX®. These biomarkers can be helpful for post-biopsy decision-making in low risk patients and post-radical prostatectomy in selected risk groups. Further studies are needed to investigate the clinical benefit of these new technologies, the financial ramifications and how they should be utilized in clinics.