Neonatal Ultrasound Results Following Very Preterm Birth Predict Adolescent Behavioral and Cognitive Outcome

This study investigated the association between different neonatal ultrasonographic classifications and adolescent cognitive, educational, and behavioral outcomes following very preterm birth. Participants included a group of 120 adolescents who were born very preterm (33 weeks of gestation), subdivided into three groups according to their neonatal cerebral ultrasound (US) classifications: (a) normal (N = 69), (b) periventricular hemorrhage (PVH, N = 37), and (c) PVH with ventricular dilatation (PVH + DIL, N = 14), and 50 controls. The cognitive functions assessed were full-scale IQ, phonological and semantic verbal fluency, and visual-motor integration. Educational outcomes included reading and spelling; behavioral outcomes were assessed with the Rutter Parents' Scale and the Premorbid Adjustment Scale (PAS). Adolescent outcome scores were compared among the four groups. A main effect for group was observed for full-scale IQ, Rutter Parents' Scale total scores, and PAS total scores, after controlling for gestational age, socioeconomic status and gender, with the PVH + DIL group showing the most impaired scores compared to the other groups. The current results demonstrate that routine neonatal ultrasound classifications are associated with later cognitive and behavioral outcome. Neonatal ultrasounds could aid in the identification of subgroups of children who are at increased risk of neurodevelopmental problems. These at risk subgroups could then be referred to appropriate early intervention services.

Consensus on Outcome Measures for Glaucoma Effectiveness Trials: Results From a Delphi and Nominal Group Technique Approaches

PURPOSE: Comparing the relative effectiveness of interventions across glaucoma trials can be problematic due to differences in definitions of outcomes. We sought to identify a key set of clinical outcomes and reach consensus on how best to measure them from the perspective of glaucoma experts.

METHODS: A 2-round electronic Delphi survey was conducted. Round 1 involved 25 items identified from a systematic review. Round 2 was developed based on information gathered in round 1. A 10-point Likert scale was used to quantify importance and consensus of outcomes (7 outcomes) and ways of measuring them (44 measures). Experts were identified through 2 glaucoma societies membership-the UK and Eire Glaucoma Society and the European Glaucoma Society. A Nominal Group Technique (NGT) followed the Delphi process. Results were analyzed using descriptive statistics.

RESULTS: A total of 65 participants completed round 1 out of 320; of whom 56 completed round 2 (86%). Agreement on the importance of outcomes was reached on 48/51 items (94%). Intraocular pressure (IOP), visual field (VF), safety, and anatomic outcomes were classified as highly important. Regarding methods of measurement of IOP, "mean follow-up IOP" using Goldmann applanation tonometry achieved the highest importance, whereas for evaluating VFs "global index mean deviation/defect (MD)" and "rate of VF progression" were the most important. Retinal nerve fiber layer (RNFL) thickness measured by optical coherence tomography (OCT) was identified as highly important. The NGT results reached consensus on "change of IOP (mean of 3 consecutive measurements taken at fixed time of day) from baseline," change of VF-MD values (3 reliable VFs at baseline and follow-up visit) from baseline, and change of RNFL thickness (2 good quality OCT images) from baseline.

CONCLUSIONS: Consensus was reached among glaucoma experts on how best to measure IOP, VF, and anatomic outcomes in glaucoma randomized controlled trials.

Towards global consensus on outcome measures for atopic eczema research: results of the HOME II meeting

The use of nonstandardized and inadequately validated outcome measures in atopic eczema trials is a major obstacle to practising evidence-based dermatology. The Harmonising Outcome Measures for Eczema (HOME) initiative is an international multiprofessional group dedicated to atopic eczema outcomes research. In June 2011, the HOME initiative conducted a consensus study involving 43 individuals from 10 countries, representing different stakeholders (patients, clinicians, methodologists, pharmaceutical industry) to determine core outcome domains for atopic eczema trials, to define quality criteria for atopic eczema outcome measures and to prioritize topics for atopic eczema outcomes research. Delegates were given evidence-based information, followed by structured group discussion and anonymous consensus voting. Consensus was achieved to include clinical signs, symptoms, long-term control of flares and quality of life into the core set of outcome domains for atopic eczema trials. The HOME initiative strongly recommends including and reporting these core outcome domains as primary or secondary endpoints in all future atopic eczema trials. Measures of these core outcome domains need to be valid, sensitive to change and feasible. Prioritized topics of the HOME initiative are the identification/development of the most appropriate instruments for the four core outcome domains. HOME is open to anyone with an interest in atopic eczema outcomes research.

Treatment of knee articular cartilage defects: surgical strategies, results and analysis of factors determining the clinical outcome

Articular cartilage lesions, with their inherent limited healing potential, are hard to treat and remain a challenging problem for orthopedic surgeons. Despite the development of several treatment strategies, the real potential of each procedure in terms of clinical benefit and effects on the joint degeneration processes is not clear. Aim of this PhD project was to evaluate the results, both in terms of clinical and imaging improvement, of new promising procedures developed to address the challenging cartilage pathology. Several studies have been followed in parallel and completed over the 3-year PhD, and are reported in detail in the following pages. In particular, the studies have been focused on the evaluation of the treatment indications of a scaffold based autologous chondrocyte implantation procedure, documenting its results for the classic indication of focal traumatic lesions, as well as its use for the treatment of more challenging patients, older, with degenerative lesions, or even as salvage procedure for more advanced stages of articular degeneration. The second field of study involved the analysis of the results obtained treating lesions of the articular surface with a new biomimetic osteochondral scaffold, which showed promise for the treatment of defects where the entire osteochondral unit is involved. Finally, a new minimally invasive procedure based on the use of growth factors derived from autologous platelets has been explored, showing results and underlining indicatios for the treatment of cartilage lesions and different stages of joint degeneration. These studies shed some light on the potential of the evaluated procedures, underlining good results as well as limits, they give some indications on the most appropriate candidates for their application, and document the current knowledge on cartilage treatment procedures suggesting the limitations that need to be addressed by future studies to improve the management of cartilage lesions.

Prosthetic rehabilitation and treatment outcome of partially edentulous patients with severe tooth wear: 3-years results

The purpose of this study was to report on the management and treatment outcomes of partially edentulous elderly patients with severe tooth wear.

Three-year results of visual outcome with disease activity-guided ranibizumab algorithm for the treatment of exudative age-related macular degeneration

PURPOSE To evaluate 3-year follow-up treatment outcomes with ranibizumab (Lucentis(®)) 0.5 mg administered either monthly or quarterly on a pro re nata (PRN) basis according to a disease activity-guided monitoring and treatment algorithm. METHODS A total of 316 treatment-naive eyes of 316 patients with exudative age-related macular degeneration met the criteria for inclusion in this retrospective, interventional case series. Patients were treated with ranibizumab 0.5 mg according to a disease activity-guided algorithm with monthly monitoring. Optical coherence tomography and fluorescein angiography were routinely used to assess disease activity: active lesions were treated with a series of three monthly injections, whereas inactive lesions were treated with quarterly injections. RESULTS Mean Early Treatment Diabetic Retinopathy Study best-corrected visual acuity improved from 52 letters at baseline to 59 letters at 12 months, achieved with a mean of 7.1 injections, 61 letters at 24 months with a mean of 5.0 injections administered in the second year and 60 letters at 36 months with a mean number of 5.2 injections. CONCLUSIONS Monthly visits and a morphology-driven PRN regimen with 3 injections in case of recurrence plus quarterly injections in case of inactive CNV resulted in an average VA gain of 7-9 letters that could be maintained over 3 years.

Social cognition as a mediator variable between neurocognition and functional outcome in schizophrenia: empirical review and new results by structural equation modeling

Cognitive impairments are currently regarded as important determinants of functional domains and are promising treatment goals in schizophrenia. Nevertheless, the exact nature of the interdependent relationship between neurocognition and social cognition as well as the relative contribution of each of these factors to adequate functioning remains unclear. The purpose of this article is to systematically review the findings and methodology of studies that have investigated social cognition as a mediator variable between neurocognitive performance and functional outcome in schizophrenia. Moreover, we carried out a study to evaluate this mediation hypothesis by the means of structural equation modeling in a large sample of 148 schizophrenia patients. The review comprised 15 studies. All but one study provided evidence for the mediating role of social cognition both in cross-sectional and in longitudinal designs. Other variables like motivation and social competence additionally mediated the relationship between social cognition and functional outcome. The mean effect size of the indirect effect was 0.20. However, social cognitive domains were differentially effective mediators. On average, 25% of the variance in functional outcome could be explained in the mediation model. The results of our own statistical analysis are in line with these conclusions: Social cognition mediated a significant indirect relationship between neurocognition and functional outcome. These results suggest that research should focus on differential mediation pathways. Future studies should also consider the interaction with other prognostic factors, additional mediators, and moderators in order to increase the predictive power and to target those factors relevant for optimizing therapy effects.

Modelling the results of health promotion activities in Switzerland: development of the Swiss Model for Outcome Classification in Health Promotion and Prevention

This paper describes the Model for Outcome Classification in Health Promotion and Prevention adopted by Health Promotion Switzerland (SMOC, Swiss Model for Outcome Classification) and the process of its development. The context and method of model development, and the aim and objectives of the model are outlined. Preliminary experience with application of the model in evaluation planning and situation analysis is reported. On the basis of an extensive literature search, the model is situated within the wider international context of similar efforts to meet the challenge of developing tools to assess systematically the activities of health promotion and prevention.

Prognostic value of the modified American College of Cardiology/American Heart Association lesion morphology classification for clinical outcome after sirolimus-eluting stent placement (results of the prospective multicenter German Cypher Registry)

The modified American College of Cardiology/American Heart Association (ACC/AHA) lesion morphology classification scheme has prognostic impact for early and late outcomes when bare-metal stents are used. Its value after drug-eluting stent placement is unknown. The predictive value of this lesion morphology classification system in patients treated using sirolimus-eluting stents included in the German Cypher Registry was prospectively examined. The study population included 6,755 patients treated for 7,960 lesions using sirolimus-eluting stents. Lesions were classified as type A, B1, B2, or C. Lesion type A or B1 was considered simple (35.1%), and type B2 or C, complex (64.9%). The combined end point of all deaths, myocardial infarction, or target vessel revascularization was seen in 2.6% versus 2.4% in the complex and simple groups, respectively (p = 0.62) at initial hospital discharge, with a trend for higher rates of myocardial infarction in the complex group. At the 6-month clinical follow-up and after adjusting for other independent factors, the composite of cumulative death, myocardial infarction, and target vessel revascularization was nonsignificantly different between groups (11.4% vs 11.2% in the complex and simple groups, respectively; odds ratio 1.08, 95% confidence interval 0.8 to 1.46). This was also true for target vessel revascularization alone (8.3% of the complex group, 9.0% of the simple group; odds ratio 0.87, 95% confidence interval 0.72 to 1.05). In conclusion, the modified ACC/AHA lesion morphology classification system has some value in determining early complications after sirolimus-eluting stent implantation. Clinical follow-up results at 6 months were generally favorable and cannot be adequately differentiated on the basis of this lesion morphology classification scheme.

T2 mapping in the knee after microfracture at 3.0 T: correlation of global T2 values and clinical outcome - preliminary results

OBJECTIVE: The aim of our study was to correlate global T2 values of microfracture repair tissue (RT) with clinical outcome in the knee joint. METHODS: We assessed 24 patients treated with microfracture in the knee joint. Magnetic resonance (MR) examinations were performed on a 3T MR unit, T2 relaxation times were obtained with a multi-echo spin-echo technique. T2 maps were obtained using a pixel wise, mono-exponential non-negative least squares fit analysis. Slices covering the cartilage RT were selected and region of interest analysis was done. An individual T2 index was calculated with global mean T2 of the RT and global mean T2 of normal, hyaline cartilage. The Lysholm score and the International Knee Documentation Committee (IKDC) knee evaluation forms were used for the assessment of clinical outcome. Bivariate correlation analysis and a paired, two tailed t test were used for statistics. RESULTS: Global T2 values of the RT [mean 49.8ms, standards deviation (SD) 7.5] differed significantly (P<0.001) from global T2 values of normal, hyaline cartilage (mean 58.5ms, SD 7.0). The T2 index ranged from 61.3 to 101.5. We found the T2 index to correlate with outcome of the Lysholm score (r(s)=0.641, P<0.001) and the IKDC subjective knee evaluation form (r(s)=0.549, P=0.005), whereas there was no correlation with the IKDC knee form (r(s)=-0.284, P=0.179). CONCLUSION: These findings indicate that T2 mapping is sensitive to assess RT function and provides additional information to morphologic MRI in the monitoring of microfracture.

Physical examination during chemoradiation predicts outcome of locally advanced head and neck cancer. Secondary results of a randomized phase III trial (SAKK 10/94)

OBJECTIVES To analyze the prognostic value of clinical tumor response during chemoradiation for locally advanced head and neck cancer. PATIENTS AND METHODS The locoregional response at 50.4Gy was assessed by physical examination (PE) in patients treated within the randomized trial SAKK 10/94 using hyperfractionated radiotherapy (RT), median total dose 74.4Gy with or without cisplatin 20mg/m(2) chemotherapy on 5 consecutive days during weeks 1 and 5 or 6 of RT. Response was classified as a complete response (CR), complete response with uncertainty (Cru), partial response (PR), stable disease (SD), or progressive disease (PD). The primary endpoint was time to treatment failure (TTF) due to any cause. Secondary endpoints included locoregional-recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS) and overall survival (OS). Univariate and multivariate Cox proportional hazards (PH) models were applied to analyze the associations between survival endpoints and clinical tumor response. RESULTS A total of 136, 131 and 97 patients were evaluable for response at the primary tumor, lymph nodes and both sites combined, respectively. At 50.4Gy 57/136 (42%), 46/131 (35%) and 21/97 (22%) patients had a good response (CR/Cru vs. PR/SD) at the primary tumor, the lymph nodes, and both sites combined, respectively. The median follow-up times were 11.4, 9.6 and 11.4years for the three groups. Good responses were all significantly associated with improved TTF, LRRFS, DMFS and OS in univariate analysis whereas good response at the primary tumor and lymph nodes remained significantly associated with TTF and OS after multivariate Cox PH models. CONCLUSIONS Locoregional response at 50.4Gy was identified as predictor of oncologic outcome. PE during treatment should not be underestimated in clinical practice.

Clinical outcome of patients with and without diabetes mellitus after percutaneous coronary intervention with the resolute zotarolimus-eluting stent: 2-year results from the prospectively pooled analysis of the international global RESOLUTE program

OBJECTIVES The aim of this study was to describe the process to obtain Food and Drug Administration (FDA) approval for the expanded indication for treatment with the Resolute zotarolimus-eluting stent (R-ZES) (Medtronic, Inc., Santa Rosa, California) in patients with coronary artery disease and diabetes. BACKGROUND The R-ZES is the first drug-eluting stent specifically indicated in the United States for percutaneous coronary intervention in patients with diabetes. METHODS We pooled patient-level data for 5,130 patients from the RESOLUTE Global Clinical Program. A performance goal prospectively determined in conjunction with the FDA was established as a rate of target vessel failure at 12 months of 14.5%. In addition to the FDA pre-specified cohort of less complex patients with diabetes (n = 878), we evaluated outcomes of the R-ZES in all 1,535 patients with diabetes compared with all 3,595 patients without diabetes at 2 years. RESULTS The 12-month rate of target vessel failure in the pre-specified diabetic cohort was 7.8% (upper 95% confidence interval: 9.51%), significantly lower than the performance goal of 14.5% (p < 0.001). After 2 years, the cumulative incidence of target lesion failure in patients with noninsulin-treated diabetes was comparable to that of patients without diabetes (8.0% vs. 7.1%). The higher risk insulin-treated population demonstrated a significantly higher target lesion failure rate (13.7%). In the whole population, including complex patients, rates of stent thrombosis were not significantly different between patients with and without diabetes (1.2% vs. 0.8%). CONCLUSIONS The R-ZES is safe and effective in patients with diabetes. Long-term clinical data of patients with noninsulin-treated diabetes are equivalent to patients without diabetes. Patients with insulin-treated diabetes remain a higher risk subset. (The Medtronic RESOLUTE Clinical Trial; NCT00248079; Randomized, Two-arm, Non-inferiority Study Comparing Endeavor-Resolute Stent With Abbot Xience-V Stent [RESOLUTE-AC]; NCT00617084; The Medtronic RESOLUTE US Clinical Trial (R-US); NCT00726453; RESOLUTE International Registry: Evaluation of the Resolute Zotarolimus-Eluting Stent System in a 'Real-World' Patient Population [R-Int]; NCT00752128; RESOLUTE Japan-The Clinical Evaluation of the MDT-4107 Drug-Eluting Coronary Stent [RJ]; NCT00927940).

Short-term functional outcome and premorbid adjustment in clinical high-risk patients. Results of the EPOS project

PURPOSE In patients with schizophrenia, premorbid psychosocial adjustment is an important predictor of functional outcome. We studied functional outcome in young clinical high-risk (CHR) patients and how this was predicted by their childhood to adolescence premorbid adjustment. METHODS In all, 245 young help-seeking CHR patients were assessed with the Premorbid Adjustment Scale, the Structured Interview for Prodromal Syndromes (SIPS) and the Schizophrenia Proneness Instrument (SPI-A). The SIPS assesses positive, negative, disorganised, general symptoms, and the Global Assessment of Functioning (GAF), the SPI-A self-experienced basic symptoms; they were carried out at baseline, at 9-month and 18-month follow-up. Transitions to psychosis were identified. In the hierarchical linear model, associations between premorbid adjustment, background data, symptoms, transitions to psychosis and GAF scores were analysed. RESULTS During the 18-month follow-up, GAF scores improved significantly, and the proportion of patients with poor functioning decreased from 74% to 37%. Poor premorbid adjustment, single marital status, poor work status, and symptoms were associated with low baseline GAF scores. Low GAF scores were predicted by poor premorbid adjustment, negative, positive and basic symptoms, and poor baseline work status. The association between premorbid adjustment and follow-up GAF scores remained significant, even when baseline GAF and transition to psychosis were included in the model. CONCLUSION A great majority of help-seeking CHR patients suffer from deficits in their functioning. In CHR patients, premorbid psychosocial adjustment, baseline positive, negative, basic symptoms and poor working/schooling situation predict poor short-term functional outcome. These aspects should be taken into account when acute intervention and long-term rehabilitation for improving outcome in CHR patients are carried out.