Adjudication Panel Research Articles

Corrigendum: Clinical Features and HLA Association of 5-Aminosalicylate (5-ASA)-induced Nephrotoxicity in Inflammatory Bowel Disease.

Background and Aims: Nephrotoxicity is a rare idiosyncratic reaction to 5-aminosalicylate (5-ASA) therapies. The aims of this study were to describe the clinical features of this complication and identify clinically useful genetic markers so that these drugs can be avoided or so that monitoring can be intensified in high-risk patients. Methods: Inflammatory bowel disease patients were recruited from 89 sites around the world. Inclusion criteria included normal renal function prior to commencing 5-ASA, ≥50% rise in creatinine any time after starting 5-ASA, and physician opinion implicating 5-ASA strong enough to justify drug withdrawal. An adjudication panel identified definite and probable cases from structured case report forms. A genome-wide association study was then undertaken with these cases and 4109 disease controls. Results: After adjudication, 151 cases of 5-ASA-induced nephrotoxicity were identified. Sixty-eight percent of cases were males, with nephrotoxicity occurring at a median age of 39.4 years (range 6–79 years). The median time for development of renal injury after commencing 5-ASA was 3.0 years (95% confidence interval [CI] 2.3–3.7). Only 30% of cases recovered completely after drug withdrawal, with 15 patients requiring permanent renal replacement therapy. A genome-wide association study identified a suggestive association in the HLA region ( p = 1×10– 7 ) with 5-ASA-induced nephrotoxicity. A sub-group analysis of patients who had a renal biopsy demonstrating interstitial nephritis ( n = 55) significantly strengthened this association ( p = 4×10–9, odds ratio 3.1). Conclusions: This is the largest and most detailed study of 5-ASA-induced nephrotoxicity to date. It highlights the morbidity associated with this condition and identifies for the first time a significant genetic predisposition to drug-induced renal injury.

Disciplinary Sanctions for Misconduct in Tennis

The decision rendered by the Internal Adjudication Panel of the International Tennis Federation (ITF) in the matter of ITF v. I. Nǎstase discusses a number of breaches of the Welfare Policy of the ITF Fed Cup Regulations by the Captain of the Romanian Fed Cup Team. From the “total disrespect to officials, the “sexual innuendo” and the “racially insensitive” comments to the “harassment of a member of the media”, this note presents and comments on how cases of misconduct in tennis are dealt with by the internal adjudication panels of the ITF. It also discusses when aggravating and mitigating circumstances are taken into consideration for the calculation of the sanction.

Autologous stem-cell transplantation in treatment-refractory Crohn's disease: an analysis of pooled data from the ASTIC trial

The randomised controlled ASTIC trial showed no benefit of mobilisation and autologous haematopoietic stem-cell transplantation (HSCT) compared with mobilisation followed by conventional therapy using a stringent primary endpoint (steroid-free clinical remission for 3 months with no endoscopic or radiological evidence of intestinal inflammation) in patients with treatment-refractory Crohn's disease. We now assess HSCT in patients enrolled in the ASTIC trial using endpoints that are traditional for clinical trials in Crohn's disease, and identify factors that predict benefit or harm. Patients who underwent mobilisation and were randomly assigned to conventional therapy in the ASTIC trial were offered HSCT at 1 year and underwent complete assessment for a further year. We report analyses of the combined cohort of patients who underwent HSCT at any time during the ASTIC trial programme. The primary outcome for this analysis was 3-month steroid-free clinical remission at 1 year after HSCT (Crohn's Disease Activity Index [CDAI] <150). We also examined the degree of endoscopic healing at 1 year. Multivariate analysis was performed to identify factors associated with achieving the primary endpoint by using logistic regression, and factors associated with experiencing a serious adverse event using Poisson regression. Participants were not masked to treatment, but the adjudication panel that reviewed radiology and endoscopy was masked to allocation and visits. All patients who underwent HSCT and had data available at baseline and 1-year follow-up were included in the primary and safety analysis. This trial is registered with ClinicalTrials.gov, number NCT00297193. Between June 28, 2007, and Sept 1, 2011, 45 patients were enrolled in the ASTIC trial from 11 European transplant units. 23 patients were randomly assigned to immediate HSCT, and 22 patients were assigned to mobilisation followed by conventional care. After completion of the ASTIC trial, 17 patients from the conventional care group received HSCT. In the combined cohort, data were available for 40 patients at baseline and 38 patients at 1 year after HSCT (one patient died, one withdrew). At 1 year after HSCT, 3-month steroid-free clinical remission was seen in 13 (38%, 95% CI 22-55) of 34 patients with available data for the whole year. Complete endoscopic healting was noted in 19 (50%, 34-66) of 38 patients. On multivariate analyses, factors associated with the primary outcome were short disease duration (odds ratio [OR] 0·64, 95% CI 0·41-0·997 per year; p=0·048) and low baseline CDAI (0·82, 0·74-0·98 per 10 units; p=0·031). 76 serious adverse events occurred in 23 of 40 patients with available data. The most common serious adverse event was infection, most of which were treatment related. Smoking and perianal disease at baseline were independent factors associated with the number of serious adverse events (OR 3·07 [95% CI 1·75-5·38; p=0·0001] for smoking and 3·97 [2·17-7·25; p<0·0001] for perianal disease) on multivariate analysis. When assessed using endpoints traditional for clinical trials of conventional therapy in Crohn's disease, HSCT resulted in clinical and endoscopic benefit, although it was associated with a high burden of adverse events. The prognostic factors identified could allow the therapy to be targeted to patients most likely to benefit and not experience serious adverse events. Broad Medical Research Program, National Institute for Health Research Senior Investigator Award, The University of Nottingham Medical School Dean's Fund, and The Nottingham University Hospitals NHS Trust Research and Development Fund.

A classification algorithm for predicting progression from normal cognition to mild cognitive impairment across five cohorts: The preclinical AD consortium

IntroductionWe established a method for diagnostic harmonization across multiple studies of preclinical Alzheimer's disease and validated the method by examining its relationship with clinical status and cognition. MethodsCognitive and clinical data were used from five studies (N = 1746). Consensus diagnoses established in each study used criteria to identify progressors from normal cognition to mild cognitive impairment. Correspondence was evaluated between these consensus diagnoses and three algorithmic classifications based on (1) objective cognitive impairment in 2+ tests only; (2) a Clinical Dementia Rating (CDR) of ≥0.5 only; and (3) both. Associations between baseline cognitive performance and cognitive change were each tested in relation to progression to algorithm-based classifications. ResultsIn each study, an algorithmic classification based on both cognitive testing cutoff scores and a CDR ≥0.5 provided optimal balance of sensitivity and specificity (areas under the curve: 0.85–0.95). Over an average 6.6 years of follow-up (up to 28 years), N = 186 initially cognitively normal participants aged on average 64 years at baseline progressed (incidence rate: 15.3 people/1000 person-years). Baseline cognitive scores and cognitive change were associated with future diagnostic status using this algorithmic classification. DiscussionBoth cognitive tests and CDR ratings can be combined across multiple studies to obtain a reliable algorithmic classification with high specificity and sensitivity. This approach may be applicable to large cohort studies and to clinical trials focused on preclinical Alzheimer's disease because it provides an alternative to implementation of a time-consuming adjudication panel.

Symulacja całkowita zgody małżeńskiej (kan. 1101 § 2 KPK) w wyroku Roty Rzymskiej c. Erlebach z 22.10.2015 r.

The author presents and provides a comment on the final sentence handed down in the third instance (the Roman Rota) in a nullitatis matrimonii case, examined ob simulationem totalem at the complainant’s request (a negative and a positive sentences were handed down in the first and second instance respectively). The key issue in this case was determining whether in the examined case the complainant’s personal goals (fines operantis), namely the desire to improve the economic situation of her and her child, can be combined with the institutional goals of marriage (fines operis). By referring to judicature of the Roman Rota and thoroughly examining the case files, the adjudication panel c. Erlebach ruled that the complainant’s personal goals were consistent with the goals of the institution of marriage and that the woman has not ruled out ipsum matrimonium. Therefore, total simulation of marriage did not happen at the time the marriage was concluded.

Predictive value of cell-surface markers in infections in critically ill patients: protocol for an observational study (ImmuNe FailurE in Critical Therapy (INFECT) Study)

IntroductionCritically ill patients are at high risk of nosocomial infections, with between 20% and 40% of patients admitted to the intensive care unit (ICU) acquiring infections. These infections result in...

Influence of the sFlt-1/PlGF Ratio on Clinical Decision-Making in Women with Suspected Preeclampsia.

ObjectiveTo evaluate the influence of the soluble fms-like tyrosine kinase 1/placental growth factor ratio in physicians’ decision making in pregnant women with signs and symptoms of preeclampsia in routine clinical practice.MethodsA multicenter, prospective, open, non-interventional study enrolled pregnant women presenting with preeclampsia signs and symptoms in several European perinatal care centers. Before the soluble fms-like tyrosine kinase 1/placental growth factor ratio result was known, physicians documented intended clinical procedures using an iPad® application (data locked/time stamped). After the result was available, clinical decisions were confirmed or revised and documented. An independent adjudication committee evaluated the appropriateness of decisions based on maternal/fetal outcomes. Clinician decision making with regard to hospitalization was the primary outcome.ResultsIn 16.9% of mothers (20/118) the hospitalization decision was changed after knowledge of the ratio. In 13 women (11.0%), the initial decision to hospitalize was changed to no hospitalization. In seven women (5.9%) the revised decision was hospitalization. All revised decisions were considered appropriate by the panel of adjudicators (McNemar test; p < 0.0001).ConclusionsThe use of the soluble fms-like tyrosine kinase 1/placental growth factor test influenced clinical decision making towards appropriate hospitalization in a considerable proportion of women with suspected preeclampsia. This is the first study to demonstrate the impact of angiogenic biomarkers on decision making in a routine clinical practice.

991 Prediction of Clinical and Endoscopic Remission After Autologous Stem Cell Transplantation in Treatment Refractory Crohn's Disease: Pooled Results From the ASTIC Trial

Introduction The randomised controlled ASTIC trial compared autologous stem cell transplantation (HSCT) with conventional care in treatment refractory Crohn’s disease (CD). Although the trial failed its ambitious primary endpoint (clinical remission for >3 months off all CD medication with no ulceration on imaging / endoscopy at 1 year) significant benefit was seen in individual components. Patients randomised to conventional care subsequently underwent HSCT. We report outcome for all patients 1 year after HSCT and identify factors that predict remission. Methods Patients with active CD who were refrctory biologics underwent cyclophosphamide mobilisation and were randomised to immediate (4 weeks) or delayed (52 weeks) HSCT. Clinical (CDAI), endoscopic (SES-CD), and quality of life scores were compared immediately prior to (baseline) and one year after HSCT. An adjudication panel blinded to allocation and visit reviewed radiology and endoscopy. Results 45 patients with successful mobilisation were randomised to early (n = 23) or delayed (n = 22) HSCT. Data from baseline and 1 year after HSCT were available for 40 patients. Compared to baseline, there were significant improvements at 1 year for CDAI, PRO2, quality of life (IBDQ, and EQ5D) and SES CD (see Table). Complete endoscopic regression (SES-CD score of 0 in all segments examined) occurred in 26%, with complete ulcer healing in 50% and partial healing (ulcers ≤5 mm in no more than 2 segments) in 82%. Clinical remission (CDAI 3 months off steroids). On univariate analysis baseline factors associated with steroid free clinical remission at 1 year include colonic localization (p = 0.006), inflammatory phenotype (p = 0.009), high SES-CD (p = 0.005). Age, CRP and early vs delayed HSCT were not significant. On multivariate analysis high baseline SES CD was associated with steroid free remission at year 1 (OR 1.21 95%CI 1.03–1.41; p = 0.017). Conclusion One year outcome in the largest reported cohort of patients undergoing HSCT for refractory Crohn’s disease shows a significant reduction in both clinical and endoscopic disease activity with an improvement in quality of life. Endoscopic severity at baseline predict outcome. Disclosure of Interest None Declared

Piper Study Rationale and Design: Characterizing the Incidence of Acute Respiratory Distress Syndrome in Hematology-Oncology Patients Following the Transfusion of Conventional or Pathogen-Reduced Platelet Components

The INTERCEPT™ Blood System (amotosalen + UVA illumination) for platelets is FDA-approved in the USA for the ex vivo preparation of pathogen-reduced, apheresis platelet components (PCs) to reduce transfusion-transmitted infection, including sepsis, and to potentially reduce the risk of transfusion-associated graft vs. host disease. Platelet transfusion is a potential risk factor for acute respiratory distress syndrome (ARDS), but the incidence of ARDS following platelet transfusion is not well-defined. A phase 3 study (SPRINT) of patients treated with INTERCEPT PCs vs. conventional PCs reported a frequency of ARDS of 1.6% vs. 0%, respectively (Snyder et al., Transfusion 2005;45:1864-1875). This unexpectedly low incidence of ARDS, owing to the lack of precise definitions, prompted the conduct of a blinded reanalysis using the American European Consensus Criteria for ARDS. Reanalysis demonstrated a frequency of ARDS of 6.0% and 4.9% for recipients of pathogen-reduced PCs and conventional PCs, respectively, with no significant treatment difference between groups (Corash et al., Blood 2011;117:1014-1020). Large scale active hemovigilance programs in Europe conducted by regulatory authorities from 2009-2014 reported no differences in the incidence of ARDS following platelet transfusion (0.33 vs. 0.32 cases per 10,000 platelets transfused). To evaluate the incidence of severe pulmonary adverse events requiring assisted ventilation in hematology-oncology (heme/onc) patients following the transfusion of apheresis derived INTERCEPT PCs compared to transfusion of conventional apheresis PCs. A prospective, non-randomized sequential cohort, open label, multi-center, non-inferiority, phase 4 surveillance study following transfusion of INTERCEPT PCs will be conducted. The patient population will be heme/onc hematopoietic stem cell transplant (HSCT) patients expected to require >1 PC transfusions. The proportion of patients requiring treatment-emergent assisted mechanical ventilation (TEAMV) during the observation period as defined by intubation or tight-fitting mask. TEAMV provides an objective measure of severe, clinically significant pulmonary injury. Patients will be assessed for TEAMV within 7 days after each study PC transfusion. 3000 patients allow for >90% power (one-sided alpha 0.025) for a non-inferiority margin of 0.023, assuming an event rate of 3.7% for the Control group. Events will be adjudicated by a blinded Pulmonary Expert Adjudication Panel. The PIPER study will address a significant deficit in the understanding of serious pulmonary events in heme/onc HSCT patients who require platelet support. It will be the first large controlled trial designed and powered to detect serious pulmonary adverse events in this patient population.

Clinical Features and HLA Association of 5-Aminosalicylate (5-ASA)-induced Nephrotoxicity in Inflammatory Bowel Disease.

Nephrotoxicity is a rare idiosyncratic reaction to 5-aminosalicylate (5-ASA) therapies. The aims of this study were to describe the clinical features of this complication and identify clinically useful genetic markers so that these drugs can be avoided or so that monitoring can be intensified in high-risk patients. Inflammatory bowel disease patients were recruited from 89 sites around the world. Inclusion criteria included normal renal function prior to commencing 5-ASA, ≥50% rise in creatinine any time after starting 5-ASA, and physician opinion implicating 5-ASA strong enough to justify drug withdrawal. An adjudication panel identified definite and probable cases from structured case report forms. A genome-wide association study was then undertaken with these cases and 4109 disease controls. After adjudication, 151 cases of 5-ASA-induced nephrotoxicity were identified. Sixty-eight percent of cases were males, with nephrotoxicity occurring at a median age of 39.4 years (range 6-79 years). The median time for development of renal injury after commencing 5-ASA was 3.0 years (95% confidence interval [CI] 2.3-3.7). Only 30% of cases recovered completely after drug withdrawal, with 15 patients requiring permanent renal replacement therapy. A genome-wide association study identified a suggestive association in the HLA region (p = 1×10(-7)) with 5-ASA-induced nephrotoxicity. A sub-group analysis of patients who had a renal biopsy demonstrating interstitial nephritis (n = 55) significantly strengthened this association (p = 4×10(-9), odds ratio 3.1). This is the largest and most detailed study of 5-ASA-induced nephrotoxicity to date. It highlights the morbidity associated with this condition and identifies for the first time a significant genetic predisposition to drug-induced renal injury.

Efficacy of transfusion with granulocytes from G-CSF/dexamethasone–treated donors in neutropenic patients with infection

AbstractHigh-dose granulocyte transfusion therapy has been available for 20 years, yet its clinical efficacy has never been conclusively demonstrated. We report here the results of RING (Resolving Infection in Neutropenia with Granulocytes), a multicenter randomized controlled trial designed to address this question. Eligible subjects were those with neutropenia (absolute neutrophil count <500/μL) and proven/probable/presumed infection. Subjects were randomized to receive either (1) standard antimicrobial therapy or (2) standard antimicrobial therapy plus daily granulocyte transfusions from donors stimulated with granulocyte colony-stimulating factor (G-CSF) and dexamethasone. The primary end point was a composite of survival plus microbial response, at 42 days after randomization. Microbial response was determined by a blinded adjudication panel. Fifty-six subjects were randomized to the granulocyte arm and 58 to the control arm. Transfused subjects received a median of 5 transfusions. Mean transfusion dose was 54.9 × 109 granulocytes. Overall success rates were 42% and 43% for the granulocyte and control groups, respectively (P > .99), and 49% and 41%, respectively, for subjects who received their assigned treatments (P = .64). Success rates for granulocyte and control arms did not differ within any infection type. In a post hoc analysis, subjects who received an average dose per transfusion of ≥0.6 × 109 granulocytes per kilogram tended to have better outcomes than those receiving a lower dose. In conclusion, there was no overall effect of granulocyte transfusion on the primary outcome, but because enrollment was half that planned, power to detect a true beneficial effect was low. RING was registered at www.clinicaltrials.gov as #NCT00627393.

The RING study: A Randomized Controlled Trial of GCSF-stimulated Granulocytes in Granulocytopenic Patients

Bacterial and fungal infections continue to be a major clinical problem in patients with prolonged severe neutropenia due to hematopoietic stem cell transplantation or aggressive chemotherapy. Although early controlled trials suggested that granulocyte transfusions were modestly effective in this setting, the doses of granulocytes provided in these studies were considered to be inadequate. Renewed interest in this therapy came with the possibility of greatly increasing the dose transfused by administering granulocyte colony-stimulating factor (G-CSF) ± dexamethasone to normal granulocyte donors. Subsequent studies showed that three to four times as many granulocytes could be collected from such donors, that these cells circulated in neutropenic recipients, and that the cells appeared to function normally both in vitro and in vivo. The evidence for clinical efficacy of this high-dose therapy has been inconclusive. The RING study is a recently completed randomized controlled study examining the efficacy of high-dose granulocyte transfusion therapy, carried out as part of the NHLBI Transfusion Medicine/Hemostasis Clinical Trials Network. Fourteen clinical sites participated. Subjects eligible for the study were those with neutropenia (ANC&lt;500) and proven/probable/presumed bacterial or fungal infection. Subjects were randomized to receive either: 1) standard antimicrobial therapy; or 2) standard antimicrobial therapy plus daily granulocyte transfusions from normal donors stimulated with G-CSF (450µg) and dexamethasone (8mg). The primary endpoint was a composite one: survival plus a microbial response, both evaluated 42 days after randomization. Microbial response was determined by a blinded adjudication panel. Desired sample size was 236 subjects, designed to have 80% power to detect a 20% difference in success rates between the treatment and control groups. One hundred and fourteen subjects were enrolled. Subjects in both arms were well matched in terms of demographics, underlying disease, types and sites of infection, and severity of illness. Of the 56 subjects randomized to the granulocyte arm, 51 received at least one transfusion. Among these 51 subjects, the median number of transfusions was five (quartiles 3 and 9) given over a median of six days (quartiles 4 and 11). The median number of granulocytes administered per transfusion was 54.9x109 (quartiles 26.1x109, 72.5x109). Among subjects with sufficient data to determine the primary outcome, success rates were 42% (20/48) and 43% (21/49) for the granulocyte and control groups, respectively (p&gt; 0.99) on Intention to Treat analysis, and 49% (17/35) and 41% (16/39), respectively, for subjects who adhered to their assigned treatments (Per Protocol analysis; p=0.64). Overall, patient infections were 36% invasive fungal, 27% invasive bacterial, 11% fungemia, and 26% bacteremia. Differences in primary endpoint success rates for granulocyte and control arms were not statistically significantly different for any infection type whether analyzed by Intention to Treat or Per Protocol. Because of the low accrual, the power of this study to detect a 20% difference in the overall success rates was reduced to approximately 40%; it is thus possible that a true effect was missed, particularly if the effect is limited to certain subject subsets. Disclosures Off Label Use: In the study being discussed, G-CSF is administered to normal blood donors. This is an off-label use of G-CSF. .

Causality assessment: Which is best-expert opinion or RUCAM?

Causality assessment: Which is best-expert opinion or RUCAM?

Diagnosing Multiple Sclerosis: Analysis of the Output from an Adjudication Panel in the Setting of a MS Diagnostic Assay Clinical Trial (P3.184)

Diagnosing Multiple Sclerosis: Analysis of the Output from an Adjudication Panel in the Setting of a MS Diagnostic Assay Clinical Trial (P3.184)

Differences in interpretation of cranial computed tomography in ED traumatic brain injury patients by expert neuroradiologists

Cranial computed tomography (CT) is generally regarded as the standard for evaluation of structural brain injury in patients with traumatic brain injury (TBI) presenting to the emergency department (ED). However, the subjective nature of the visual interpretations of CT scans and the qualitative nature of reporting may lead to poor interrater reliability. This is significant because CT positive scans include a continuum of structural injury with differences in treatment. The purpose of the present study was to evaluate the consistency of readings of head CT scans obtained within 24 hours after mild TBI in the ED, as assessed by an independent adjudication panel of 3 experienced neuroradiologists. In 80.1% of the cases, all 3 adjudicators agreed with the determination of the presence of structural injury. However, when interrater agreement was assessed with respect to the specific classification of the injury, agreement was poor, with a κ of 0.3 (0.29-0.316; confidence interval [CI] 95%). When classification was collapsed, considering only the presence or absence of hematomas, agreement among all 3 adjudicators improved to 55%, but the κ of 0.355, (0.332-0.78; CI 95%) was still only fair. The data suggest the need for improved recognition and quantification of specific structural injuries in the TBI population for better identification of patients requiring clinical intervention.

A Large Case-Control Study Reveals a Positive Association Between Bisphosphonate Use and Delayed Dental Healing and Osteonecrosis of the Jaw

This study sought to investigate, using a case-control study design, the association between bisphosphonate therapy and delayed dental healing and osteonecrosis of the jaw. Identification of potential cases of delayed dental healing was by consecutive screening of Specialist Oral and Maxillofacial and Special Needs Dentist clinic records for patients aged older than 50 years, during a 6-month window, in Victoria, Australia. Cases were confirmed by a case adjudication panel blinded to bisphosphonate status. Cases associated with malignancy or local radiotherapy were excluded. Controls were matched for age, sex, and source of dental referral (1:4, n = 160 controls). Variables of interest were dental precipitants, dental clinic type, smoking history, and medical comorbidities. A total of 4212 of 22,358 patients met inclusion criteria, of which 69 were potential cases with 40 (0.95%) confirmed cases. The odds ratio (OR) for developing delayed dental healing when taking an oral bisphosphonate was 13.1 (95% confidence interval [CI] 4.4 to 39.3; p < 0.001). There were no cases associated with intravenous bisphosphonate use. There was some evidence of an interaction with age, sex, and clinic type. When adjusted for smoking, the estimated odds ratio was 11.6 (95% CI 1.9 to 69.4; p = 0.01). There was an association between having another illness and delayed dental healing (OR = 2.3; 95% CI 1.0 to 5.2). A dental precipitant was present in 39 of 40 (97.5%) delayed dental healing cases. An important association between bisphosphonate use and delayed dental healing in the setting of benign bone disease, predominately in individuals with a dental precipitant, has been demonstrated.

Awards galore … the results are in!

Welcome, dear readers, to the first issue of Volume 23 of Laser Therapy, and to the first issue of 2014, the Year of the Horse, which is now well and truly under way. “March,” they say, “comes in like a lion and goes out like a lamb.” There will be many people worldwide who have suffered from the intense weather phenomena, like raging Australian forest fires, the North American plunging temperatures and blizzards and the widespread hurricane-strength storms and flooding in the UK, who will be wishing that the “lamb” part of the saying should come true as quickly as possible. Our thoughts go out to all those who have suffered from calamitous weather-related events in these first months of 2014. As I write, Japan is unseasonably cold for March, with snow storms here and there. However, Nature presses on, and the cherry blossoms will very soon explode in Kyushu, to the south of Japan, so we can look forward to warmer and sunnier weather It is hard to believe that this is the 23rd year in which the journal has appeared, and it seems almost yesterday when we were discussing the possibility of publishing the journal with John Wiley and Sons of Chichester, UK: that process actually started in 1987, and we have come a long way since then. Now the journal has reached new peaks of excellence, and has garnered international recognition by the leading indexing services. None of this could have happened without papers to publish, and that is still the case, dear readers, so please, send in your papers! As you read this we are already one-quarter of the way through 2014, which means that you only have 9 months left to get your paper in to us, and qualify for entry to our two awards for selected papers: the Laser Therapy Best/Good Papers Award and the newly founded Ming-Chien Kao Award for Young Researchers. All you have to do is get you clinical or research findings down on paper, and send them in! The results of the adjudication panels for papers published in 2013 have been scored and totaled, so without further ado, here they are!

Public Reporting of Health Care–Associated Surveillance Data: Recommendations From the Healthcare Infection Control Practices Advisory Committee

Health care-associated infection (HAI) rates are used as measures of a health care facility's quality of patient care. Recently, these outcomes have been used to publicly rank quality efforts and determine facility reimbursement. The value of comparing HAI rates among health care facilities is limited by many factors inherent to HAI surveillance, and incentives that reward low HAI rates can lead to unintended consequences that can compromise medical care surveillance efforts, such as the use of clinical adjudication panels to veto events that meet HAI surveillance definitions.The Healthcare Infection Control Practices Advisory Committee, a federal advisory committee that provides advice and guidance to the Centers for Disease Control and Prevention (CDC) and the Secretary of the Department of Health and Human Services about strategies for surveillance, prevention, and control of HAIs, assessed the challenges associated with using HAI surveillance data for external quality reporting, including the unintended consequences of clinician veto and clinical adjudication panels. Discussions with stakeholder liaisons and committee members were then used to formulate recommended standards for the use of HAI surveillance data for external facility assessment to ensure valid comparisons and to provide as level a playing field as possible.The final recommendations advocate for consistent, objective, and independent application of CDC HAI definitions with concomitant validation of HAIs and surveillance processes. The use of clinician veto and adjudication is discouraged.

PEG-J Administration of Therapeutic Agents for Neurological Disorders: Levodopa-Carbidopa Intestinal Gel for Advanced Parkinsonʼs Disease

Purpose: To determine whether PEG-J administration of levodopa-carbidopa intestinal gel (LCIG) is an effective method for the treatment of advanced Parkinson's disease (PD). Methods: Levodopa is the most effective treatment for PD. With advanced disease, irregular gastric emptying impedes standard oral levodopa effectiveness leading to “On”/”Off” motor fluctuations and dyskinesias. Two phase 3 clinical studies enrolled advanced PD patients with persistent motor fluctuations despite optimized oral therapy. For this novel treatment, involving the collaboration of neurologists and gastroenterologists, all patients underwent a PEG-J procedure for infusion of LCIG (or placebo gel) directly to the proximal jejunum. A 12-week, randomized, double-blind, double-dummy trial compared the effectiveness of LCIG with standard oral levodopa (LC-oral) at reducing motor fluctuations and improving quality of life. A 54-week open-label international trial examined the long-term safety and efficacy of LCIG. “Off” time (when medication is no longer effective and motor symptoms return), the Unified Parkinson's Disease Rating Scale (UPDRS) and the 39-item Parkinson's Disease Questionnaire (PDQ-39) were examined. Adverse events (AEs) were recorded. Results: 71 patients were enrolled in the double-blind, double-dummy trial (n=37 LCIG, 34 LC-Oral), with a mean PD duration of 10.9 years. The reduction in “off” time (P<0.01), improvement in UPDRS Part II (activities of daily living) score (P<0.01) and improvement in PDQ-39 Summary Index (P<0.05) was greater in the LCIG group than in the LC-oral group. Three hundred fifty four patients were enrolled in the long-term, open-label study. As with the double-blind trial, “off” time, UPDRS Part II score and PDQ-39 Summary Index versus baseline were improved at all visits (through Week 54; P<0.01). Most patients (97% in double-blind, 91% in open-label) experienced at least 1 AE; serious AEs occurred in 17% (double-blind) and 31% (open-label). AEs led to discontinuation in 4.2% (double-blind) and 7.6% (open-label). Most AEs were known AEs associated with either levodopa, underlying PD or the procedure and the device. Conclusion: Intrajejunal infusion of LCIG via PEG-J is a novel approach for the long-term delivery of medication in gel form, which improved motor fluctuations and the quality of life in advanced PD patients with limited treatment options. The range of PEG-J complications was within standard ranges reported in the literature and was not increased in this ambulatory patient cohort. Disclosure - Michael Epstein: Dr. Epstein served on the data adjudication panel for this study and has received compensation from AbbVie for serving as a consultant. Dr. Epstein also serves as a lecturer for AbbVie. David Johnson: Dr. Johnson served on the data adjudication panel for this study and has received compensation from AbbVie for serving as a consultant. Robert Hawes: Dr. Hawes served on the data adjudication panel for this study and has received compensation from AbbVie for serving as a consultant. Nathan Schmulewitz: Dr. Schmulewitz serves as a medical advisor and speaker for AbbVie. Arvydas Vanagunas: Dr. Vanagunas has received compensation from AbbVie and CVS Caremark's Pharmacy & Therapeutics Committee for serving as a consultant and has been a scientific advisory board member for AbbVie. Cindy Zadikoff: CZ was a study investigator and has received compensation from AbbVie for serving as a consultant and participating in scientific advisory boards. Rod Gossen: served as executive secretary for this study and is employed by a consulting agency under contract with AbbVie. Susan Eaton, Krai Chatamra, Weining Robieson, Jordan Dubow and Janet Benesh are employees of AbbVie and hold AbbVie stock and/or stock options. AbbVie participated in the study design, research, data collection, analysis and interpretation of data, writing, reviewing, and approving the publication. Michelle M. Koutsantonis, of AbbVie, provided medical writing assistance in the development of this publication. This research was supported by an industry grant from AbbVie.

638 5-Aminosalicylate (5-ASA) Induced Nephrotoxicity in Inflammatory Bowel Disease

Introduction Nephrotoxicity is a rare idiosyncratic reaction to 5-ASA therapy. The precise pathogenic mechanisms are unknown. This study aims to a) describe the clinical features of this rare complication b) explore underlying mechanisms and c) identify clinically useful predictive genetic markers so these drugs can be avoided, or monitoring intensified, in high-risk patients. Here we report the clinical features. Methods Patients were identified and recruited from 185 sites (130 UK). Inclusion criteria included normal renal function prior to commencing 5-ASA, ≥50% rise in creatinine after starting 5-ASA and medical opinion implicating 5-ASA justified drug withdrawal. An adjudication panel assessed causality from case report forms using the validated Liverpool Adverse Drug Reaction Causality Assessment Tool. Results 154 patients were recruited. 19 patients were excluded following adjudication. The cohort included patients with Crohn’s disease, ulcerative colitis and indeterminate colitis (42%, 55%, 4% respectively). 74% of cases were male. Nephrotoxicity was seen with all aminosalicylates including 1 patient treated with topical therapy only. Nephrotoxicity occurred at a median age of 36.5 yrs (range 15.4–88.4 yrs). Two patients had a confirmed family history of 5-ASA-induced nephrotoxicity. 78% were detected by routine blood monitoring. Only 45% of cases recovered completely after drug withdrawal, with 18 requiring renal replacement therapy (14 transplantation). The median time for peak creatinine after commencing 5-ASA was 3.5 yrs (range 0.16–43.4 yrs). There was no evidence that time on 5-ASA treatment was associated with a higher peak creatinine or the likelihood of full recovery (p = 0.87). Women were more likely to reach full recovery than men (p = 0.00148; OR 8.26; CI 2.46–34.94). There was no evidence that early withdrawal of 5-ASA led to a higher likelihood of complete recovery. There was no difference in recovery between the three disease groups on logistic regression analysis. Conclusion This is the largest and most detailed study of 5-ASA induced nephrotoxicity to date. Whilst the incidence is low, the morbidity is high with 13% of patients requiring renal replacement therapy and 55% of patients failing to return to a normal creatinine after 5-ASA withdrawal. The next step is to carry forward these patients to a genome-wide association analysis, to be performed in February 2013. Disclosure of Interest None Declared