Trends and outcomes in the use of surgery and radiation for the treatment of locally advanced esophageal cancer: a propensity score adjusted analysis of the surveillance, epidemiology, and end results registry from 1998 to 2008

We examined outcomes and trends in surgery and radiation use for patients with locally advanced esophageal cancer, for whom optimal treatment isn't clear. Trends in surgery and radiation for patients with T1-T3N1M0 squamous cell or adenocarcinoma of the mid or distal esophagus in the Surveillance, Epidemiology, and End Results database from 1998 to 2008 were analyzed using generalized linear models including year as predictor; Surveillance, Epidemiology, and End Results doesn't record chemotherapy data. Local treatment was unimodal if patients had only surgery or radiation and bimodal if they had both. Five-year cancer-specific survival (CSS) and overall survival (OS) were analyzed using propensity-score adjusted Cox proportional-hazard models. Overall 5-year survival for the 3295 patients identified (mean age 65.1 years, standard deviation 11.0) was 18.9% (95% confidence interval: 17.3-20.7). Local treatment was bimodal for 1274 (38.7%) and unimodal for 2021 (61.3%) patients; 1325 (40.2%) had radiation alone and 696 (21.1%) underwent only surgery. The use of bimodal therapy (32.8-42.5%, P = 0.01) and radiation alone (29.3-44.5%, P < 0.001) increased significantly from 1998 to 2008. Bimodal therapy predicted improved CSS (hazard ratios [HR]: 0.68, P < 0.001) and OS (HR: 0.58, P < 0.001) compared with unimodal therapy. For the first 7 months (before survival curve crossing), CSS after radiation therapy alone was similar to surgery alone (HR: 0.86, P = 0.12) while OS was worse for surgery only (HR: 0.70, P = 0.001). However, worse CSS (HR: 1.43, P < 0.001) and OS (HR: 1.46, P < 0.001) after that initial timeframe were found for radiation therapy only. The use of radiation to treat locally advanced mid and distal esophageal cancers increased from 1998 to 2008. Survival was best when both surgery and radiation were used.

Early Detection and Treatment of Psychosis: The Bern Child and Adolescent Psychiatric Perspective

Commonly conceptualized as neurodevelopmental disorders of yet poorly understood aetiology, schizophrenia and other nonorganic psychoses remain one of the most debilitating illnesses with often poor outcome despite all progress in treatment of the manifest disorder. Drawing on the frequent poor outcome of psychosis and its association with the frequently extended periods of untreated first-episode psychosis (FEP) including its prodrome, an early detection and treatment of both the FEP and the preceding at-risk mental state (ARMS) have been increasingly studied. Thereby both approaches are confronted with different problems, for example, treatment engagement in FEP and predictive accuracy in ARMS. They share, however, the problems related to the lack of understanding of developmental, that is, age-related, peculiarities and of the presentation and natural course of their cardinal symptoms in the community. Most research on early detection and intervention in FEP and ARMS is still related to clinical psychiatric samples, and little is known about symptom presentation and burden and help-seeking in the general population related to these experiences. Furthermore, in particular in the early detection of an ARMS, studies often address adolescents and young adults alike without consideration of developmental characteristics, thereby applying risk criteria that have been developed predominately in adults. Combining our earlier experiences described in this paper in child and adolescent, and general psychiatry as well as in both lines of research, that is, on early psychosis and its treatment and on the early detection of psychosis, in particular in its very early states by subjective disturbances in terms of basic symptoms, age-related developmental and epidemiological aspects have therefore been made the focus of our current studies in Bern, thus making our line of research unique

State of the art of integrated therapy approaches in the treatment of schizophrenia: empirical evidence and clinical relevance

Objective: Integrated behavior therapy approaches are defined by the combination of behavioral and or cognitive interventions targeting neurocognition combined with other goal-oriented treatment targets such as social cognition, social skills, or educational issues. The Integrated Psychological Therapy Program (IPT) represents one of the very first behavior therapy approaches combining interventions of neurocognition, social cognition, and social competence. This comprehensive group-based bottom-up and top-down approach consists of five subprograms, each with incremental steps. IPT has been successfully implemented in several countries in Europe, America, Australia and in Asia. IPT worked as a model for some other approaches designed in the USA. IPT was undergone two further developments: based on the social competence part of IPT, the three specific therapy programs focusing residential, occupational or recreational topics were developed. Recently, the cognitive part of INT was rigorously expanded into the Integrated Neurocognitive Therapy (INT) designed exclusively for outpatient treatment: INT includes interventions targeting all neurocognitive and social cognitive domains defined by the NIMH-MATRICS initiative. These group and partially PC-based exercises are structured into four therapy modules, each starting with exercises on neurocognitive domains followed by social cognitive targets. Efficacy: The evidence of integrated therapy approaches and its advantage compared to of one-track interventions was becoming a discussion tool in therapy research as well as in mental health systems. Results of meta-analyses support superiority of integrated approaches compared to one-track interventions in more distal outcome areas such as social functioning. These results are in line with the large body of 37 independent IPT studies in 12 countries. Moreover, IPT research indicates the maintenance of therapy effects after the end of therapy and some evidence generalization effects. Additionally, the international randomized multi-center study on INT with 169 outpatients strongly supports the successful therapy of integrated therapy in proximal and distal outcome such as significant effects in cognition, functioning and negative symptoms. Clinical implication: therapy research as well as expert’s clinical experience recommends integrated therapy approaches such as IPT to be successful agents within multimodal psychiatric treatment concepts. Finally, integrated group therapy based on cognitive remediation seems to motivate and stimulate schizophrenia inpatients and outpatients to more successful and independent life also demanded by the recovery movement.

Incidence and Imaging Outcomes of Acute Scaffold Disruption and Late Structural Discontinuity After Implantation of the Absorb Everolimus-Eluting Fully Bioresorbable Vascular Scaffold: Optical Coherence Tomography Assessment in the ABSORB Cohort B Trial (A Clinical Evaluation of the Bioabsorbable Everolimus Eluting Coronary Stent System in the Treatment of Patients With De Novo Native Coronary Artery Lesions).

OBJECTIVES This study sought to describe the frequency and clinical impact of acute scaffold disruption and late strut discontinuity of the second-generation Absorb bioresorbable polymeric vascular scaffolds (Absorb BVS, Abbott Vascular, Santa Clara, California) in the ABSORB (A Clinical Evaluation of the Bioabsorbable Everolimus Eluting Coronary Stent System in the Treatment of Patients With De Novo Native Coronary Artery Lesions) cohort B study by optical coherence tomography (OCT) post-procedure and at 6, 12, 24, and 36 months. BACKGROUND Fully bioresorbable scaffolds are a novel approach to treatment for coronary narrowing that provides transient vessel support with drug delivery capability without the long-term limitations of metallic drug-eluting stents. However, a potential drawback of the bioresorbable scaffold is the potential for disruption of the strut network when overexpanded. Conversely, the structural discontinuity of the polymeric struts at a late stage is a biologically programmed fate of the scaffold during the course of bioresorption. METHODS The ABSORB cohort B trial is a multicenter single-arm trial assessing the safety and performance of the Absorb BVS in the treatment of 101 patients with de novo native coronary artery lesions. The current analysis included 51 patients with 143 OCT pullbacks who underwent OCT at baseline and follow-up. The presence of acute disruption or late discontinuities was diagnosed by the presence on OCT of stacked, overhung struts or isolated intraluminal struts disconnected from the expected circularity of the device. RESULTS Of 51 patients with OCT imaging post-procedure, acute scaffold disruption was observed in 2 patients (3.9%), which could be related to overexpansion of the scaffold at the time of implantation. One patient had a target lesion revascularization that was presumably related to the disruption. Of 49 patients without acute disruption, late discontinuities were observed in 21 patients. There were no major adverse cardiac events associated with this finding except for 1 patient who had a non-ischemia-driven target lesion revascularization. CONCLUSIONS Acute scaffold disruption is a rare iatrogenic phenomenon that has been anecdotally associated with anginal symptoms, whereas late strut discontinuity is observed in approximately 40% of patients and could be viewed as a serendipitous OCT finding of a normal bioresorption process without clinical implications. (ABSORB Clinical Investigation, Cohort B [ABSORB B]; NCT00856856).

Dynamic intraligamentary stabilization and primary repair: A new concept for the treatment of knee dislocation.

BACKGROUND Traumatic knee dislocation represents a rare but devastating injury. Several controversies persist regarding type of treatment, surgical timing, graft selection, repair versus reconstruction of the medial and lateral structures, surgical techniques and postoperative rehabilitation. A new technique for primary ACL stabilization, dynamic intaligamentary stabilization (DIS) was developed at the authors' institution. The purpose of this study was to analyze the clinical and radiological outcomes of surgically treated traumatic knee dislocations by means of the DIS technique for the ACL, primary suturing for PCL, MCL and LCL. METHODS Between 2009 and 2012, 35 patients treated surgically for traumatic knee dislocation with primary anterior cruciate ligament (ACL) reconstruction with DIS, suturing of the posterior cruciate ligament (PCL) and primary complete repair of collaterals, were evaluated clinically (IKDC score, SF12 health survey, Lysholm score, Tegner score) and radiologically with a mean follow up of 2.2 years (range 1.00-3.50 years) years. Instrumented anterior-posterior translation was measured (KT-2000). RESULTS Anterior/posterior translation (KT-2000) for the healthy and injured limb was 4.8mm (range 3-8mm) and 7.3mm (range 5-10) (89N) respectively. Valgus and varus stress testing in 30° flexion was normal in 26 (75%) and 29 (83%) patients, respectively. The IKDC score was B in 29 (83%) and C in 6 (17%) patients, while the mean Tegner score was 6 (range 4-8). The mean Lysholm score was 90.83 (range 81-95) and mean SF-12 physical and mental scores were 54.1 (range 45-60) and 51.0 (range 39-62) respectively. In 2 patients, a secondary operation was performed. CONCLUSIONS Early, one stage reconstruction with DIS can achieve good functional results and patient satisfaction with overall restoration of sports and working capacity without graft requirements.

ERS task force statement: diagnosis and treatment of primary spontaneous pneumothorax.

Primary spontaneous pneumothorax (PSP) affects young healthy people with a significant recurrence rate. Recent advances in treatment have been variably implemented in clinical practice. This statement reviews the latest developments and concepts to improve clinical management and stimulate further research.The European Respiratory Society's Scientific Committee established a multidisciplinary team of pulmonologists and surgeons to produce a comprehensive review of available scientific evidence.Smoking remains the main risk factor of PSP. Routine smoking cessation is advised. More prospective data are required to better define the PSP population and incidence of recurrence. In first episodes of PSP, treatment approach is driven by symptoms rather than PSP size. The role of bullae rupture as the cause of air leakage remains unclear, implying that any treatment of PSP recurrence includes pleurodesis. Talc poudrage pleurodesis by thoracoscopy is safe, provided calibrated talc is available. Video-assisted thoracic surgery is preferred to thoracotomy as a surgical approach.In first episodes of PSP, aspiration is required only in symptomatic patients. After a persistent or recurrent PSP, definitive treatment including pleurodesis is undertaken. Future randomised controlled trials comparing different strategies are required.

Resolving diffusion in clay minerals at different time scales: Combination of experimental and modeling approaches

Since no single experimental or modeling technique provides data that allow a description of transport processes in clays and clay minerals at all relevant scales, several complementary approaches have to be combined to understand and explain the interplay between transport relevant phenomena. In this paper molecular dynamics simulations (MD) were used to investigate the mobility of water in the interlayer of montmorillonite (Mt), and to estimate the influence of mineral surfaces and interlayer ions on the water diffusion. Random Walk (RW) simulations based on a simplified representation of pore space in Mt were used to estimate and understand the effect of the arrangement of Mt particles on the meso- to macroscopic diffusivity of water. These theoretical calculations were complemented with quasielastic neutron scattering (QENS) measurements of aqueous diffusion in Mt with two pseudo-layers of water performed at four significantly different energy resolutions (i.e. observation times). The size of the interlayer and the size of Mt particles are two characteristic dimensions which determine the time dependent behavior of water diffusion in Mt. MD simulations show that at very short time scales water dynamics has the characteristic features of an oscillatory motion in the cage formed by neighbors in the first coordination shell. At longer time scales, the interaction of water with the surface determines the water dynamics, and the effect of confinement on the overall water mobility within the interlayer becomes evident. At time scales corresponding to an average water displacement equivalent to the average size of Mt particles, the effects of tortuosity are observed in the meso- to macroscopic pore scale simulations. Consistent with the picture obtained in the simulations, the QENS data can be described using a (local) 3D diffusion at short observation times, whereas at sufficiently long observation times a 2D diffusive motion is clearly observed. The effects of tortuosity measured in macroscopic tracer diffusion experiments are in qualitative agreement with RW simulations. By using experimental data to calibrate molecular and mesoscopic theoretical models, a consistent description of water mobility in clay minerals from the molecular to the macroscopic scale can be achieved. In turn, simulations help in choosing optimal conditions for the experimental measurements and the data interpretation. (C) 2014 Elsevier B.V. All rights reserved.

First generation versus second generation drug-eluting stents for the treatment of bifurcations: 5-year follow-up of the LEADERS all-comers randomized trial.

BACKGROUND Historically, percutaneous coronary intervention (PCI) of bifurcation lesions was associated with worse procedural and clinical outcomes when compared with PCI of non-bifurcation lesions. Newer generation drug-eluting stents (DES) might improve long-term clinical outcomes after bifurcation PCI. METHODS AND RESULTS The LEADERS trial was a 10-center, assessor-blind, non-inferiority, all-comers trial, randomizing 1,707 patients to treatment with a biolimus A9(TM) -eluting stent (BES) with an abluminal biodegradable polymer or a sirolimus-eluting stent (SES) with a durable polymer (ClinicalTrials.gov Identifier: NCT00389220). Five-year clinical outcomes were compared between patients with and without bifurcation lesions and between BES and SES in the bifurcation lesion subgroup. There were 497 (29%) patients with at least 1 bifurcation lesion (BES = 258; SES = 239). At 5-year follow-up, the composite endpoint of cardiac death, myocardial infarction (MI) and clinically-indicated (CI) target vessel revascularization (TVR) was observed more frequently in the bifurcation group (26.6% vs. 22.4%, P = 0.049). Within the bifurcation lesion subgroup, no differences were observed in (cardiac) death or MI rates between BES and SES. However, CI target lesion revascularization (TLR) (10.1% vs. 15.9%, P = 0.0495), and CI TVR (12.0% vs. 19.2%, P = 0.023) rates were significantly lower in the BES group. Definite/probable stent thrombosis (ST) rate was numerically lower in the BES group (3.1% vs. 5.9%, P = 0.15). Very late (>1 year) definite/probable ST rates trended to be lower with BES (0.4% vs. 3.1%, P = 0.057). CONCLUSIONS In the treatment of bifurcation lesions, use of BES led to superior long-term efficacy compared with SES. Safety outcomes were comparable between BES and SES, with an observed trend toward a lower rate of very late definite/probable ST between 1 and 5 years with the BES. © 2015 Wiley Periodicals, Inc.

Surgery for Stage IIIA Non-Small-cell Lung Cancer: Lack of Predictive and Prognostic Factors Identifying Any Subgroup of Patients Benefiting From It.

Although a trimodality regimen for patients with stage IIIA/pN2 non-small-cell lung cancer (NSCLC) has been variably used owing to limited evidence for its benefits, it remains unknown whether any patient subgroup actually receives benefit from such an approach. To explore this question, the published data were reviewed from 1990 to 2015 to identify the possible predictors and prognosticators in this setting. Overall survival was the endpoint of our study. Of 27 identified studies, none had studied the predictors of improved outcomes with trimodality treatment. Of the potential patient- and tumor-related prognosticators, age, gender, and histologic type were the most frequently formally explored. However, none of the 3 was found to influence overall survival. The most prominent finding of the present review was the substantial lack of data supporting a trimodality treatment approach in any patient subgroup. As demonstrated in completed prospective randomized studies, the use of surgery for stage IIIA NSCLC should be limited to well-defined clinical trials.

Description of the SAGhE Cohort: A Large European Study of Mortality and Cancer Incidence Risks after Childhood Treatment with Recombinant Growth Hormone.

BACKGROUND The long-term safety of growth hormone treatment is uncertain. Raised risks of death and certain cancers have been reported inconsistently, based on limited data or short-term follow-up by pharmaceutical companies. PATIENTS AND METHODS The SAGhE (Safety and Appropriateness of Growth Hormone Treatments in Europe) study assembled cohorts of patients treated in childhood with recombinant human growth hormone (r-hGH) in 8 European countries since the first use of this treatment in 1984 and followed them for cause-specific mortality and cancer incidence. Expected rates were obtained from national and local general population data. The cohort consisted of 24,232 patients, most commonly treated for isolated growth failure (53%), Turner syndrome (13%) and growth hormone deficiency linked to neoplasia (12%). This paper describes in detail the study design, methods and data collection and discusses the strengths, biases and weaknesses consequent on this. CONCLUSION The SAGhE cohort is the largest and longest follow-up cohort study of growth hormone-treated patients with follow-up and analysis independent of industry. It forms a major resource for investigating cancer and mortality risks in r-hGH patients. The interpretation of SAGhE results, however, will need to take account of the methods of cohort assembly and follow-up in each country.

Non-surgical treatment of pain associated with posterior tibial tendon dysfunction: study protocol for a randomised clinical trial

BACKGROUND Symptoms associated with pes planovalgus or flatfeet occur frequently, even though some people with a flatfoot deformity remain asymptomatic. Pes planovalgus is proposed to be associated with foot/ankle pain and poor function. Concurrently, the multifactorial weakness of the tibialis posterior muscle and its tendon can lead to a flattening of the longitudinal arch of the foot. Those affected can experience functional impairment and pain. Less severe cases at an early stage are eligible for non-surgical treatment and foot orthoses are considered to be the first line approach. Furthermore, strengthening of arch and ankle stabilising muscles are thought to contribute to active compensation of the deformity leading to stress relief of soft tissue structures. There is only limited evidence concerning the numerous therapy approaches, and so far, no data are available showing functional benefits that accompany these interventions. METHODS After clinical diagnosis and clarification of inclusion criteria (e.g., age 40-70, current complaint of foot and ankle pain more than three months, posterior tibial tendon dysfunction stage I & II, longitudinal arch flattening verified by radiography), sixty participants with posterior tibial tendon dysfunction associated complaints will be included in the study and will be randomly assigned to one of three different intervention groups: (i) foot orthoses only (FOO), (ii) foot orthoses and eccentric exercise (FOE), or (iii) sham foot orthoses only (FOS). Participants in the FOO and FOE groups will be allocated individualised foot orthoses, the latter combined with eccentric exercise for ankle stabilisation and strengthening of the tibialis posterior muscle. Participants in the FOS group will be allocated sham foot orthoses only. During the intervention period of 12 weeks, all participants will be encouraged to follow an educational program for dosed foot load management (e.g., to stop activity if they experience increasing pain). Functional impairment will be evaluated pre- and post-intervention by the Foot Function Index. Further outcome measures include the Pain Disability Index, Visual Analogue Scale for pain, SF-12, kinematic data from 3D-movement analysis and neuromuscular activity during level and downstairs walking. Measuring outcomes pre- and post-intervention will allow the calculation of intervention effects by 3×3 Analysis of Variance (ANOVA) with repeated measures. DISCUSSION The purpose of this randomised trial is to evaluate the therapeutic benefit of three different non-surgical treatment regimens in participants with posterior tibial tendon dysfunction and accompanying pes planovalgus. Furthermore, the analysis of changes in gait mechanics and neuromuscular control will contribute to an enhanced understanding of functional changes and eventually optimise conservative management strategies for these patients. TRIAL REGISTRATION ClinicalTrials.gov Protocol Registration System: ClinicalTrials.gov ID NCT01839669.

Retention in care during the first 3 years of antiretroviral therapy for women in Malawi's option B+ programme: an observational cohort study

Background Studies of Malawi's option B+ programme for HIV-positive pregnant and breastfeeding women have reported high loss to follow-up during pregnancy and at the start of antiretroviral therapy (ART), but few data exist about retention during breastfeeding and after weaning. We examined loss to follow-up and retention in care in patients in the option B+ programme during their first 3 years on ART. Methods We analysed two data sources: aggregated facility-level data about patients in option B+ who started ART between Oct 1, 2011, and June 30, 2012, at 546 health facilities; and patient-level data from 20 large facilities with electronic medical record system for HIV-positive women who started ART between Sept 1, 2011, and Dec 31, 2013, under option B+ or because they had WHO clinical stages 3 or 4 disease or had CD4 counts of less than 350 cells per μL. We used facility-level data to calculate representative estimates of retention and loss to follow-up. We used patient-level data to study temporal trends in retention, timing of loss to follow-up, and predictors of no follow-up and loss to follow-up. We defined patients who were more than 60 days late for their first follow-up visit as having no follow-up and patients who were more than 60 days late for a subsequent visit as being lost to follow-up. We calculated proportions and cumulative probabilities of patients who had died, stopped ART, had no follow-up, were lost to follow-up, or were retained alive on ART for 36 months. We calculated odds ratios and hazard ratios to examine predictors of no follow-up and loss to follow-up. Findings Analysis of facility-level data about patients in option B+ who had not transferred to a different facility showed retention in care to be 76·8% (20 475 of 26 658 patients) after 12 months, 70·8% (18 306 of 25 849 patients) after 24 months, and 69·7% (17 787 of 25 535 patients) after 36 months. Patient-level data included 29 145 patients. 14 630 (50·2%) began treatment under option B+. Patients in option B+ had a higher risk of having no follow-up and, for the first 2 years of ART, higher risk of loss to follow-up than did patients who started ART because they had CD4 counts less than 350 cells per μL or WHO clinical stage 3 or 4 disease. Risk of loss to follow-up during the third year was low and similar for patients retained for 2 years. Retention rates did not change as the option B+ programme matured. Interpretation Our data suggest that pregnant and breastfeeding women who start ART immediately after they are diagnosed with HIV can be retained on ART through the option B+ programme, even after many have stopped breastfeeding. Interventions might be needed to improve retention in the first year on ART in option B+. Funding Bill & Melinda Gates Foundation, Partnerships for Enhanced Engagement in Research Health, and National Institute of Allergy and Infectious Diseases.

Effectiveness of non-steroidal anti-inflammatory drugs for the treatment of pain in knee and hip osteoarthritis: a network meta-analysis.

BACKGROUND Non-steroidal anti-inflammatory drugs (NSAIDs) are the backbone of osteoarthritis pain management. We aimed to assess the effectiveness of different preparations and doses of NSAIDs on osteoarthritis pain in a network meta-analysis. METHODS For this network meta-analysis, we considered randomised trials comparing any of the following interventions: NSAIDs, paracetamol, or placebo, for the treatment of osteoarthritis pain. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) and the reference lists of relevant articles for trials published between Jan 1, 1980, and Feb 24, 2015, with at least 100 patients per group. The prespecified primary and secondary outcomes were pain and physical function, and were extracted in duplicate for up to seven timepoints after the start of treatment. We used an extension of multivariable Bayesian random effects models for mixed multiple treatment comparisons with a random effect at the level of trials. For the primary analysis, a random walk of first order was used to account for multiple follow-up outcome data within a trial. Preparations that used different total daily dose were considered separately in the analysis. To assess a potential dose-response relation, we used preparation-specific covariates assuming linearity on log relative dose. FINDINGS We identified 8973 manuscripts from our search, of which 74 randomised trials with a total of 58 556 patients were included in this analysis. 23 nodes concerning seven different NSAIDs or paracetamol with specific daily dose of administration or placebo were considered. All preparations, irrespective of dose, improved point estimates of pain symptoms when compared with placebo. For six interventions (diclofenac 150 mg/day, etoricoxib 30 mg/day, 60 mg/day, and 90 mg/day, and rofecoxib 25 mg/day and 50 mg/day), the probability that the difference to placebo is at or below a prespecified minimum clinically important effect for pain reduction (effect size [ES] -0·37) was at least 95%. Among maximally approved daily doses, diclofenac 150 mg/day (ES -0·57, 95% credibility interval [CrI] -0·69 to -0·46) and etoricoxib 60 mg/day (ES -0·58, -0·73 to -0·43) had the highest probability to be the best intervention, both with 100% probability to reach the minimum clinically important difference. Treatment effects increased as drug dose increased, but corresponding tests for a linear dose effect were significant only for celecoxib (p=0·030), diclofenac (p=0·031), and naproxen (p=0·026). We found no evidence that treatment effects varied over the duration of treatment. Model fit was good, and between-trial heterogeneity and inconsistency were low in all analyses. All trials were deemed to have a low risk of bias for blinding of patients. Effect estimates did not change in sensitivity analyses with two additional statistical models and accounting for methodological quality criteria in meta-regression analysis. INTERPRETATION On the basis of the available data, we see no role for single-agent paracetamol for the treatment of patients with osteoarthritis irrespective of dose. We provide sound evidence that diclofenac 150 mg/day is the most effective NSAID available at present, in terms of improving both pain and function. Nevertheless, in view of the safety profile of these drugs, physicians need to consider our results together with all known safety information when selecting the preparation and dose for individual patients. FUNDING Swiss National Science Foundation (grant number 405340-104762) and Arco Foundation, Switzerland.

Dynamic Intraligamentary Stabilization (DIS) for treatment of acute anterior cruciate ligament ruptures: case series experience of the first three years.

BACKGROUND In recent years, the scientific discussion has focused on new strategies to enable a torn anterior cruciate ligament (ACL) to heal into mechanically stable scar tissue. Dynamic intraligamentary stabilization (DIS) was first performed in a pilot study of 10 patients. The purpose of the current study was to evaluate whether DIS would lead to similarly sufficient stability and good clinical function in a larger case series. METHODS Acute ACL ruptures were treated by using an internal stabilizer, combined with anatomical repositioning of torn bundles and microfracturing to promote self-healing. Clinical assessment (Tegner, Lysholm, IKDC, and visual analogue scale [VAS] for patient satisfaction scores) and assessment of knee laxity was performed at 3, 6, 12, and 24 months. A one-sample design with a non-inferiority margin was chosen to compare the preoperative and postoperative IKDS and Lysholm scores. RESULTS 278 patients with a 6:4 male to female ratio were included. Average patient age was 31 years. Preoperative mean IKDC, Lysholm, and Tegner scores were 98.8, 99.3, and 5.1 points, respectively. The mean anteroposterior (AP) translation difference from the healthy contralateral knee was 4.7 mm preoperatively. After DIS treatment, the mean 12-month IKDC, Lysholm, and Tegner scores were 93.6, 96.2, and 4.9 points, respectively, and the mean AP translation difference was 2.3 mm. All these outcomes were significantly non-inferior to the preoperative or healthy contralateral values (p < 0.0001). Mean patient satisfaction was 8.8 (VAS 0-10). Eight ACL reruptures occurred and 3 patients reported insufficient subjective stability of the knee at the end of the study period. CONCLUSIONS Anatomical repositioning, along with DIS and microfracturing, leads to clinically stable healing of the torn ACL in the large majority of patients. Most patients exhibited almost normal knee function, reported excellent satisfaction, and were able to return to their previous levels of sporting activity. Moreover, this strategy resulted in stable healing of all sutured menisci, which could lower the rate of osteoarthritic changes in future. The present findings support the discussion of a new paradigm in ACL treatment based on preservation and self-healing of the torn ligament.

Survival of gastrointestinal and stromal tumor patients at UT M.D. Anderson Cancer Center

Objective. Gastrointestinal Stromal Tumors (GISTs) are rare mesenchymal tumors of the gastrointestinal (GI) tract with spindled cell, epithelioid, or occasionally pleomorphic morphology. The primary objective of this paper is to describe the demographic and clinical characteristics and survival among GIST patients registered at the University of Texas M.D. Anderson Cancer Center (MDACC). ^ Methods. This cohort study includes 783 consecutive patients diagnosed with GIST from 1995 to 2007. Demographic, clinical and survival information were obtained from the MDACC cancer registry. ^ Statistical Analysis. Kaplan-Meier survival curves, univariate and multivariate Cox proportional hazards analysis were conducted to estimate survival and identify prognostic clinical factors associated with survival. Results. The age at diagnosis of MDACC GIST cases ranged from 17 to 91 with a mean of 57 years and a male-to-female ratio of 1.3:1. The racial distribution was whites 77%, African-Americans 9.5%, Hispanics 9.3% and other races 4.2%. Fifty per cent of the GISTs arose from stomach, 35% small intestine, 7% retroperitoneal space, 6% colorectal and 2% were omentum and mesentery. About half of the tumors were less than 10 cm in size. Fifty eight per cent of the tumors were localized whereas 36% were metastatic. MDACC GIST patients were generally comparable to SEER patients, but, on the average, were 7 years younger than SEER patients and were predominantly whites. ^ Stratification of 783 GIST cases by year of diagnosis based on the introduction of imatinib treatment in 2000 revealed that 60% of the GIST cases were first diagnosed between 2000 and 2007 whereas, 40% were first diagnosed between 1995 and 1999. There was a significant difference between the two cohorts in the distribution of race, GIST symptom, tumor size, tumor site, and stage of the tumor at diagnosis. The 1- and 5-year survival was 93% and 59% in the 1995–2007 cohort. Multivariate Cox regression analysis identified age at diagnosis (p<0.001), female sex (p=0.047), tumor size (p=0.07), multiple cancers (p=0.002), and GIST diagnosed between 2000 and 2007 (p<0.001) were significantly associated with survival. Approximately, 58% of the cases were treated with imatinib whereas 42% did not receive imatinib in 2000–2005 cohort. There was a significant difference in survival between imatinib and non-imatinib groups and in the distribution of tumor size categories, stage of the tumor at diagnosis and cancers before the diagnosis of GIST. The 1- and 5-year survival for imatinib patients was 99% and 73% and was 91% and 63% for non-imatinib patients. Multivariate Cox regression analysis of the 2000–2007 cohort identified, age at diagnosis and tumor stage as possible prognostic factors associated with survival.^