Temperamental Dimension and Anxiety Problems in a Clinical Sample of Three- to Six-year old Children: A Study of Variables

In the last few years, many researchers have studied the presence of common dimensions of temperament in subjects with symptoms of anxiety. The aim of this study is to examine the association between temperamental dimensions (high negative affect and activity level) and anxiety problems in clinicalpreschool children. A total of 38 children, ages 3 to 6 years, from the Infant and Adolescent Mental Health Center of Girona and the Center of Diagnosis and Early Attention of Sabadell and Olot were evaluated by parents and psychologists. Their parents completed several screening scales and, subsequently, clinical child psychopathology professionals carried out diagnostic interviews with children from the sample who presented signs of anxiety. Findings showed that children with high levels of negative affect and low activity level have pronounced symptoms of anxiety. However, children with anxiety disorders do not present different temperament styles from their peers without these pathologies

ACTG-HIV symptoms changes in patients switched to RPV/FTC/TDF due to previous intolerance to CART. Interim analysis of the PRO-STR study.

INTRODUCTION Tolerability and convenience are crucial aspects for the long-term success of combined antiretroviral therapy (cART). The aim of this study was to investigate the impact in routine clinical practice of switching to the single tablet regimen (STR) RPV/FTC/TDF in patients with intolerance to previous cART, in terms of patients' well-being, assessed by several validated measures. METHODS Prospective, multicenter study. Adult HIV-infected patients with viral load under 1.000 copies/mL while receiving a stable ART for at least the last three months and switched to RPV/FTC/TDF due to intolerance of previous regimen, were included. Analyses were performed by ITT. Presence/magnitude of symptoms (ACTG-HIV Symptom Index), quality of life (EQ-5D, EUROQoL & MOS-HIV), adherence (SMAQ), preference of treatment and perceived ease of medication (ESTAR) through 48 weeks were performed. RESULTS Interim analysis of 125 patients with 16 weeks of follow up was performed. 100 (80%) were male, mean age 46 years. Mean CD4 at baseline was 629.5±307.29 and 123 (98.4%) had viral load <50 copies/mL; 15% were HCV co-infected. Ninety two (73.6%) patients switched from a NNRTI (84.8% from EFV/FTC/TDF) and 33 (26.4%) from a PI/r. The most frequent reasons for switching were psychiatric disorders (51.2%), CNS adverse events (40.8%), gastrointestinal (19.2%) and metabolic disorders (19.2%). At the time of this analysis (week 16), four patients (3.2%) discontinued treatment: one due to adverse events, two virologic failures and one with no data. A total of 104 patients (83.2%) were virologically suppressed (<50 copies/mL). The average degree of discomfort in the ACTG-HIV Symptom Index significantly decreased from baseline (21±15.55) to week 4 (10.89±12.36) & week 16 (10.81±12.62), p<0.001. In all the patients, quality of life tools showed a significant benefit in well-being of the patients (Table 1). Adherence to therapy significantly and progressively increased (SMAQ) from baseline (54.4%) to week 4 (68%), p<0.001 and to week 16 (72.0%), p<0.001. CONCLUSIONS Switching to RPV/FTC/TDF from another ARV regimen due to toxicity, significantly improved the quality of life of HIV-infected patients, both in mental and physical components, and improved adherence to therapy while maintaining a good immune and virological response.

Unanswered clinical questions in the management of cardiometabolic risk in the elderly: a statement of the Spanish society of internal medicine.

BACKGROUND Despite the progressive increase in life expectancy and the relationship between aging with multi-morbidities and the increased use of healthcare resources, current clinical practice guidelines (CPG) on cardiometabolic risk cannot be adequately applied to elderly subjects with multiple chronic conditions. Its management frequently becomes complicated by both, an excessive use of medications that may lead to overtreatment, drug interactions and increased toxicity, and errors in dosage and non-compliance. Concerned by this gap, the Spanish Society of Internal Medicine created a group of independent experts on cardiometabolic risk who discussed what they considered to be unanswered questions in the management of elderly patients. DISCUSSION Current guidelines do not specifically address the problem of elderly with multiple chronic conditions. For this reason, the combined use of the limited available evidence, clinical experience and common sense, could all help us to address this unmet need. In very old people, life expectancy and functionality are the most important factors for guiding potential treatments. Their higher propensity to develop serious adverse events and their shorter lifespan could prevent them from obtaining the potential benefits of the interventions administered. SUMMARY In this document, experts on cardiometabolic risk factors have established a number of consensual recommendations that have taken into account international guidelines and clinical experience, and have also considered the more effective use of healthcare resources. This document is intended to provide general recommendations for clinicians and to promote the effective use of procedures and medications.

EFNS guidelines on the clinical management of amyotrophic lateral sclerosis (MALS)--revised report of an EFNS task force.

BACKGROUND: The evidence base for the diagnosis and management of amyotrophic lateral sclerosis (ALS) is weak. OBJECTIVES: To provide evidence-based or expert recommendations for the diagnosis and management of ALS based on a literature search and the consensus of an expert panel. METHODS: All available medical reference systems were searched, and original papers, meta-analyses, review papers, book chapters and guidelines recommendations were reviewed. The final literature search was performed in February 2011. Recommendations were reached by consensus. RECOMMENDATIONS: Patients with symptoms suggestive of ALS should be assessed as soon as possible by an experienced neurologist. Early diagnosis should be pursued, and investigations, including neurophysiology, performed with a high priority. The patient should be informed of the diagnosis by a consultant with a good knowledge of the patient and the disease. Following diagnosis, the patient and relatives/carers should receive regular support from a multidisciplinary care team. Medication with riluzole should be initiated as early as possible. Control of symptoms such as sialorrhoea, thick mucus, emotional lability, cramps, spasticity and pain should be attempted. Percutaneous endoscopic gastrostomy feeding improves nutrition and quality of life, and gastrostomy tubes should be placed before respiratory insufficiency develops. Non-invasive positive-pressure ventilation also improves survival and quality of life. Maintaining the patient's ability to communicate is essential. During the entire course of the disease, every effort should be made to maintain patient autonomy. Advance directives for palliative end-of-life care should be discussed early with the patient and carers, respecting the patient's social and cultural background.

Acupuncture and rehabilitation of the painful shoulder: study protocol of an ongoing multicentre randomised controlled clinical trial [ISRCTN28687220]

BACKGROUND Although the painful shoulder is one of the most common dysfunctions of the locomotor apparatus, and is frequently treated both at primary healthcare centres and by specialists, little evidence has been reported to support or refute the effectiveness of the treatments most commonly applied. According to the bibliography reviewed, physiotherapy, which is the most common action taken to alleviate this problem, has not yet been proven to be effective, because of the small size of sample groups and the lack of methodological rigor in the papers published on the subject. No reviews have been made to assess the effectiveness of acupuncture in treating this complaint, but in recent years controlled randomised studies have been made and these demonstrate an increasing use of acupuncture to treat pathologies of the soft tissues of the shoulder. In this study, we seek to evaluate the effectiveness of physiotherapy applied jointly with acupuncture, compared with physiotherapy applied with a TENS-placebo, in the treatment of painful shoulder caused by subacromial syndrome (rotator cuff tendinitis and subacromial bursitis). METHODS/DESIGN Randomised controlled multicentre study with blind evaluation by an independent observer and blind, independent analysis. A study will be made of 465 patients referred to the rehabilitation services at participating healthcare centres, belonging to the regional public health systems of Andalusia and Murcia, these patients presenting symptoms of painful shoulder and a diagnosis of subacromial syndrome (rotator cuff tendinitis and subacromial bursitis). The patients will be randomised into two groups: 1) experimental (acupuncture + physiotherapy); 2) control (TENS-placebo + physiotherapy); the administration of rescue medication will also be allowed. The treatment period will have a duration of three weeks. The main result variable will be the change produced on Constant's Shoulder Function Assessment (SFA) Scale; as secondary variables, we will record the changes in diurnal pain intensity on a visual analogue scale (VAS), nocturnal pain intensity on the VAS, doses of non-steroid anti-inflammatory drugs (NSAIDs) taken during the study period, credibility scale for the treatment, degree of improvement perceived by the patient and degree of improvement perceived by the evaluator. A follow up examination will be made at 3, 6 and 12 months after the study period has ended. Two types of population will be considered for analysis: per protocol and per intention to treat. DISCUSSION The discussion will take into account the limitations of the study, together with considerations such as the choice of a simple, safe method to treat this shoulder complaint, the choice of the control group, and the blinding of the patients, evaluators and those responsible for carrying out the final analysis.

Clinical intervals and diagnostic characteristics in a cohort of prostate cancer patients in Spain: a multicentre observational study.

BACKGROUND Little is known about the healthcare process for patients with prostate cancer, mainly because hospital-based data are not routinely published. The main objective of this study was to determine the clinical characteristics of prostate cancer patients, the, diagnostic process and the factors that might influence intervals from consultation to diagnosis and from diagnosis to treatment. METHODS We conducted a multicentre, cohort study in seven hospitals in Spain. Patients' characteristics and diagnostic and therapeutic variables were obtained from hospital records and patients' structured interviews from October 2010 to September 2011. We used a multilevel logistic regression model to examine the association between patient care intervals and various variables influencing these intervals (age, BMI, educational level, ECOG, first specialist consultation, tumour stage, PSA, Gleason score, and presence of symptoms) and calculated the odds ratio (OR) and the interquartile range (IQR). To estimate the random inter-hospital variability, we used the median odds ratio (MOR). RESULTS 470 patients with prostate cancer were included. Mean age was 67.8 (SD: 7.6) years and 75.4 % were physically active. Tumour size was classified as T1 in 41.0 % and as T2 in 40 % of patients, their median Gleason score was 6.0 (IQR:1.0), and 36.1 % had low risk cancer according to the D'Amico classification. The median interval between first consultation and diagnosis was 89 days (IQR:123.5) with no statistically significant variability between centres. Presence of symptoms was associated with a significantly longer interval between first consultation and diagnosis than no symptoms (OR:1.93, 95%CI 1.29-2.89). The median time between diagnosis and first treatment (therapeutic interval) was 75.0 days (IQR:78.0) and significant variability between centres was found (MOR:2.16, 95%CI 1.45-4.87). This interval was shorter in patients with a high PSA value (p = 0.012) and a high Gleason score (p = 0.026). CONCLUSIONS Most incident prostate cancer patients in Spain are diagnosed at an early stage of an adenocarcinoma. The period to complete the diagnostic process is approximately three months whereas the therapeutic intervals vary among centres and are shorter for patients with a worse prognosis. The presence of prostatic symptoms, PSA level, and Gleason score influence all the clinical intervals differently.

Clinical and epidemiological features and prognosis of complicated pyelonephritis: a prospective observational single hospital-based study.

BACKGROUND Complicated pyelonephritis (cPN), a common cause of hospital admission, is still a poorly-understood entity given the difficulty involved in its correct definition. The aim of this study was to analyze the main epidemiological, clinical, and microbiological characteristics of cPN and its prognosis in a large cohort of patients with cPN. METHODS We conducted a prospective, observational study including 1325 consecutive patients older than 14 years diagnosed with cPN and admitted to a tertiary university hospital between 1997-2013. After analyzing the main demographic, clinical and microbiological data, covariates found to be associated with attributable mortality in univariate analysis were included in a multivariate logistic regression model. RESULTS Of the 1325 patients, 689 (52%) were men and 636 (48%) women; median age 63 years, interquartile range [IQR] (46.5-73). Nine hundred and forty patients (70.9%) had functional or structural abnormalities in the urinary tract, 215 (16.2%) were immunocompromised, 152 (11.5%) had undergone a previous urinary tract instrumentation, and 196 (14.8%) had a long-term bladder catheter, nephrostomy tube or ureteral catheter. Urine culture was positive in 813 (67.7%) of the 1251 patients in whom it was done, and in the 1032 patients who had a blood culture, 366 (34%) had bacteraemia. Escherichia coli was the causative agent in 615 episodes (67%), Klebsiella spp in 73 (7.9%) and Proteus ssp in 61 (6.6%). Fourteen point one percent of GNB isolates were ESBL producers. In total, 343 patients (25.9%) developed severe sepsis and 165 (12.5%) septic shock. Crude mortality was 6.5% and attributable mortality was 4.1%. Multivariate analysis showed that an age >75 years (OR 2.77; 95% CI, 1.35-5.68), immunosuppression (OR 3.14; 95% CI, 1.47-6.70), and septic shock (OR 58.49; 95% CI, 26.6-128.5) were independently associated with attributable mortality. CONCLUSIONS cPN generates a high morbidity and mortality and likely a great consumption of healthcare resources. This study highlights the factors directly associated with mortality, though further studies are needed in the near future aimed at identifying subgroups of low-risk patients susceptible to outpatient management.

Canakinumab relieves symptoms of acute flares and improves health-related quality of life in patients with difficult-to-treat Gouty Arthritis by suppressing inflammation: results of a randomized, dose-ranging study.

INTRODUCTION: We report the impact of canakinumab, a fully human anti-interleukin-1β monoclonal antibody, on inflammation and health-related quality of life (HRQoL) in patients with difficult-to-treat Gouty Arthritis. METHODS: In this eight-week, single-blind, double-dummy, dose-ranging study, patients with acute Gouty Arthritis flares who were unresponsive or intolerant to--or had contraindications for--non-steroidal anti-inflammatory drugs and/or colchicine were randomized to receive a single subcutaneous dose of canakinumab (10, 25, 50, 90, or 150 mg) (N = 143) or an intramuscular dose of triamcinolone acetonide 40 mg (N = 57). Patients assessed pain using a Likert scale, physicians assessed clinical signs of joint inflammation, and HRQoL was measured using the 36-item Short-Form Health Survey (SF-36) (acute version). RESULTS: At baseline, 98% of patients were suffering from moderate-to-extreme pain. The percentage of patients with no or mild pain was numerically greater in most canakinumab groups compared with triamcinolone acetonide from 24 to 72 hours post-dose; the difference was statistically significant for canakinumab 150 mg at these time points (P < 0.05). Treatment with canakinumab 150 mg was associated with statistically significant lower Likert scores for tenderness (odds ratio (OR), 3.2; 95% confidence interval (CI), 1.27 to 7.89; P = 0.014) and swelling (OR, 2.7; 95% CI, 1.09 to 6.50, P = 0.032) at 72 hours compared with triamcinolone acetonide. Median C-reactive protein and serum amyloid A levels were normalized by seven days post-dose in most canakinumab groups, but remained elevated in the triamcinolone acetonide group. Improvements in physical health were observed at seven days post-dose in all treatment groups; increases in scores were highest for canakinumab 150 mg. In this group, the mean SF-36 physical component summary score increased by 12.0 points from baseline to 48.3 at seven days post-dose. SF-36 scores for physical functioning and bodily pain for the canakinumab 150 mg group approached those for the US general population by seven days post-dose and reached norm values by eight weeks post-dose. CONCLUSIONS: Canakinumab 150 mg provided significantly greater and more rapid reduction in pain and signs and symptoms of inflammation compared with triamcinolone acetonide 40 mg. Improvements in HRQoL were seen in both treatment groups with a faster onset with canakinumab 150 mg compared with triamcinolone acetonide 40 mg. TRIAL REGISTRATION: clinicaltrials.gov: NCT00798369.

Interindividual variability of the clinical pharmacokinetics of methadone: implications for the treatment of opioid dependence

Methadone is widely used for the treatment of opioid dependence. Although in most countries the drug is administered as a racemic mixture of (R)- and (S)- methadone, (R)-methadone accounts for most, if not all, of the opioid effects. Methadone can be detected in the blood 15-45 minutes after oral administration, with peak plasma concentration at 2.5-4 hours. Methadone has a mean bioavailability of around 75% (range 36-100%). Methadone is highly bound to plasma proteins, in particular to alpha(1)-acid glycoprotein. Its mean free fraction is around 13%, with a 4-fold interindividual variation. Its volume of distribution is about 4 L/kg (range 2-13 L/kg). The elimination of methadone is mediated by biotransformation, followed by renal and faecal excretion. Total body clearance is about 0.095 L/min, with wide interindividual variation (range 0.02-2 L/min). Plasma concentrations of methadone decrease in a biexponential manner, with a mean value of around 22 hours (range 5-130 hours) for elimination half-life. For the active (R)-enantiomer, mean values of around 40 hours have been determined. Cytochrome P450 (CYP) 3A4 and to a lesser extent 2D6 are probably the main isoforms involved in methadone metabolism. Rifampicin (rifampin), phenobarbital, phenytoin, carbamazepine, nevirapine, and efavirenz decrease methadone blood concentrations, probably by induction of CYP3A4 activity, which can result in severe withdrawal symptoms. Inhibitors of CYP3A4, such as fluconazole, and of CYP2D6, such as paroxetine, increase methadone blood concentrations. There is an up to 17-fold interindividual variation of methadone blood concentration for a given dosage, and interindividual variability of CYP enzymes accounts for a large part of this variation. Since methadone probably also displays large interindividual variability in its pharmacodynamics, methadone treatment must be individually adapted to each patient. Because of the high morbidity and mortality associated with opioid dependence, it is of major importance that methadone is used at an effective dosage in maintenance treatment: at least 60 mg/day, but typically 80-100 mg/day. Recent studies also show that a subset of patients might benefit from methadone dosages larger than 100 mg/day, many of them because of high clearance. In clinical management, medical evaluation of objective signs and subjective symptoms is sufficient for dosage titration in most patients. However, therapeutic drug monitoring can be useful in particular situations. In the case of non-response trough plasma concentrations of 400 microg/L for (R,S)-methadone or 250 microg/L for (R)-methadone might be used as target values.

Small bowel bacterial overgrowth is found in 71% of IBS patients and associated symptoms respond well to Rifaximin in a phase IV trial

Background a nd A ims: The prevalence of small intestinal bowel bacterial o vergrowth (SIBO) i n patients w ith irritable bowel syndrome (IBS) ranges from 43% to 78% as determined by t he lactulose hydrogen breath (LHBT) t est. Although rifaximine, a non-absorbable antibiotic, h as b een able to decrease I BS s ymptoms i n placebo-controlled r andomized trials, these results were not repeated in phase IV studies. We aimed to assess the prevalence of SIBO in an IBS cohort and to evaluate the response to rifaximin. Methods: I BS p atients f ulfilled Rome III criteria, had an absence of alarm symptoms, n ormal f ecal c alproectin, and normal e ndoscopic workup. They underwent lactulose hydrogen breath t esting (LHBT) for SIBO diagnosis. P atients with SIBO were t reated w ith rifaximine tablets f or 14 d ays. Symptoms were a ssessed by q uestionnaires before rifaximin treatment and at week 6. Results: Hundred-fifty IBS patients were enrolled (76% female, mean age 44 ± 16 years), of whom 106 (71%) were diagnosed with SIBO and consequently treated with rifaximine. Rifaximine treatment s ignificantly reduced the following symptoms as assessed by t he s ymptom q uestionnaire: bloating (5.5 ± 2.6 before vs. 3 .6 ± 2.7 after treatment, p <0.001), flatulence (5 ± 2.7 vs. 4 ± 2.7, p = 0.015), diarrhea (2.9 ± 2.4 vs. 2 ± 2.4, p = 0.005), abdominal pain (4.8 ± 2.7 vs. 3.3 ± 2.5, p <0.001) and resulted in improved overall well-being (3.9 ± 2.4 vs. 2.7 ± 2.3, p <0.001). The LHBT was repeated 2-4 weeks after rifaximine treatment in 6 5/93 (70%) patients. Eradication of SIBO was documented in 85% of all patients (55/65). Conclusions: The results o f our phase IV trial i ndicate that a high proportion of IBS p atients t ested positive f or SIBO. I BS symptoms w ere significantly diminished following a 2-week treatment with rifaximine.

Validation study of the French version of the observer-rater scales measuring coping and cognitive errors (CE-CAP) on a non-clinical population

This study examined the validity and reliability of the French version of two observer-rated measures developed to assess cognitive errors (cognitive errors rating system [CERS]) [6] and coping action patterns (coping action patterns rating system [CAPRS]) [22,24]. The CE measures 14 cognitive errors, broken down according to their valence positive or negative (see the definitions by A.T. Beck), and the CAP measures 12 coping categories, based on an comprehensive review literature, each broken down into three levels of action (affective, behavioural, cognitive). Thirty (N = 30) subjects recruited in a community sample participated in the study. They were interviewed according to a standardized clinical protocol: these interviews were transcribed and analysed with both observer-rated systems. Results showed that the inter-rater reliability of the two measures is good and that their internal validity is satisfactory, due to a non-significant canonical correlation between CAP and CE. With regard to discriminant validity, we found a non-significant canonical correlation between CAPRS and CISS, one of most widely used self-report questionnaire measuring coping. The same can be said for the correlation with a self-report questionnaire measuring symptoms (SCL-90-R). These results confirm the absence of confounds in the assessment of cognitive errors and of coping as assessed by these observer-rated scales and add an argument in favour of the French validation of the CE-CAP rating scales. (C) 2010 Elsevier Masson SAS. All rights reserved.

Feasibility and clinical outcomes when using practice guidelines for evaluation of fever in returning travelers and migrants : a validation study.

BACKGROUND: Practice guidelines for examining febrile patients presenting upon returning from the tropics were developed to assist primary care physicians in decision making. Because of the low level of evidence available in this field, there was a need to validate them and assess their feasibility in the context they have been designed for. OBJECTIVES: The objectives of the study were to (1) evaluate physicians' adherence to recommendations; (2) investigate reasons for non-adherence; and (3) ensure good clinical outcome of patients, the ultimate goal being to improve the quality of the guidelines, in particular to tailor them for the needs of the target audience and population. METHODS: Physicians consulting the guidelines on the Internet (www.fevertravel.ch) were invited to participate in the study. Navigation through the decision chart was automatically recorded, including diagnostic tests performed, initial and final diagnoses, and clinical outcomes. The reasons for non-adherence were investigated and qualitative feedback was collected. RESULTS: A total of 539 physician/patient pairs were included in this study. Full adherence to guidelines was observed in 29% of the cases. Figure-specific adherence rate was 54.8%. The main reasons for non-adherence were as follows: no repetition of malaria tests (111/352) and no presumptive antibiotic treatment for febrile diarrhea (64/153) or abdominal pain without leukocytosis (46/101). Overall, 20% of diversions from guidelines were considered reasonable because there was an alternative presumptive diagnosis or the symptoms were mild, which means that the corrected adherence rate per case was 40.6% and corrected adherence per figure was 61.7%. No death was recorded and all complications could be attributed to the underlying illness rather than to adherence to guidelines. CONCLUSIONS: These guidelines proved to be feasible, useful, and leading to good clinical outcomes. Almost one third of physicians strictly adhered to the guidelines. Other physicians used the guidelines not to forget specific diagnoses but finally diverged from the proposed attitudes. These diversions should be scrutinized for further refinement of the guidelines to better fit to physician and patient needs.

Double-bundle transtibial posterior cruciate ligament reconstruction with a tendon-patellar bone-semitendinosus tendon autograft: clinical results with a minimum of 2 years' follow-up.

PURPOSE: The purpose of this study was to evaluate the clinical and subjective outcomes after arthroscopic-assisted double-bundle posterior cruciate ligament (PCL) reconstruction. METHODS: A series of 15 patients with grade III isolated chronic PCL tears underwent double-bundle PCL reconstruction. Of these patients, 8 (53%) had simultaneous fractures. The mean time from accident to surgery was 10.8 months (range, 8 to 15 months). The mean age at the time of surgery was 28.2 years (range, 17 to 43 years). All of the patients reported knee insecurity during activities of daily living or light sporting activities, with associated anterior knee pain in 5 patients. Preoperatively, posterolateral or posteromedial corner injuries were ruled out through accurate clinical examination. The knees were assessed before surgery and at a mean follow-up of 3.2 years (range, 2 to 5 years) with a physical examination, 4 different rating scales, and stress radiographs obtained with a Telos device (Telos, Marburg, Germany). RESULTS: Postoperative physical examination revealed a reduction of the posterior drawer and tibial step-off in all cases, although the posterior laxity was not completely normalized. Nevertheless, the patients were subjectively better after surgery. The subjective International Knee Documentation Committee score was significantly ameliorated. With regard to the objective International Knee Documentation Committee score, 6 knees (40%) were graded as abnormal because of posterior displacement of 6 mm or greater on follow-up stress radiographs with the Telos device. On the Lysholm knee scoring scale, the score was excellent in 13% of patients and good in 87%. The mean score on the Hospital for Special Surgery knee ligament rating scale was 85.8. The Tegner activity score showed an amelioration after surgery, but no patient resumed his or her preinjury level of activities. The postoperative stress radiographs revealed an improvement in posterior instability of 50% or more in all but 3 knees (20%). CONCLUSIONS: Our technique of double-bundle PCL reconstruction produced a significant reduction in knee symptoms and allowed the patients to return to moderate or strenuous activity, although the posterior tibial translation was not completely normalized and our results appear to be no better than the results of single-bundle PCL reconstruction. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

New validated prognostic models and prognostic calculators in patients with low-grade gliomas diagnosed by central pathology review: a pooled analysis of EORTC/RTOG/NCCTG phase III clinical trials.

Background In a previous study, the European Organisation for Research and Treatment of Cancer (EORTC) reported a scoring system to predict survival of patients with low-grade gliomas (LGGs). A major issue in the diagnosis of brain tumors is the lack of agreement among pathologists. New models in patients with LGGs diagnosed by central pathology review are needed. Methods Data from 339 EORTC patients with LGGs diagnosed by central pathology review were used to develop new prognostic models for progression-free survival (PFS) and overall survival (OS). Data from 450 patients with centrally diagnosed LGGs recruited into 2 large studies conducted by North American cooperative groups were used to validate the models. Results Both PFS and OS were negatively influenced by the presence of baseline neurological deficits, a shorter time since first symptoms (<30 wk), an astrocytic tumor type, and tumors larger than 5 cm in diameter. Early irradiation improved PFS but not OS. Three risk groups have been identified (low, intermediate, and high) and validated. Conclusions We have developed new prognostic models in a more homogeneous LGG population diagnosed by central pathology review. This population better fits with modern practice, where patients are enrolled in clinical trials based on central or panel pathology review. We could validate the models in a large, external, and independent dataset. The models can divide LGG patients into 3 risk groups and provide reliable individual survival predictions. Inclusion of other clinical and molecular factors might still improve models' predictions.