International Society of Urological Pathology (ISUP) Consensus Conference on Handling and Staging of Radical Prostatectomy Specimens. Working group 5: surgical margins.

The 2009 International Society of Urological Pathology Consensus Conference in Boston, made recommendations regarding the standardization of pathology reporting of radical prostatectomy specimens. Issues relating to surgical margin assessment were coordinated by working group 5. Pathologists agreed that tumor extending close to the 'capsular' margin, yet not to it, should be reported as a negative margin, and that locations of positive margins should be indicated as either posterior, posterolateral, lateral, anterior at the prostatic apex, mid-prostate or base. Other items of consensus included specifying the extent of any positive margin as millimeters of involvement; tumor in skeletal muscle at the apical perpendicular margin section, in the absence of accompanying benign glands, to be considered organ confined; and that proximal and distal margins be uniformly referred to as bladder neck and prostatic apex, respectively. Grading of tumor at positive margins was to be left to the discretion of the reporting pathologists. There was no consensus as to how the surgical margin should be regarded when tumor is present at the inked edge of the tissue, in the absence of transected benign glands at the apical margin. Pathologists also did not achieve agreement on the reporting approach to benign prostatic glands at an inked surgical margin in which no carcinoma is present.

International Society of Urological Pathology (ISUP) Consensus Conference on Handling and Staging of Radical Prostatectomy Specimens. Working group 3: extraprostatic extension, lymphovascular invasion and locally advanced disease.

The International Society of Urological Pathology Consensus Conference on Handling and Staging of Radical Prostatectomy Specimens in Boston made recommendations regarding the standardization of pathology reporting of radical prostatectomy specimens. Issues relating to extraprostatic extension (pT3a disease), bladder neck invasion, lymphovascular invasion and the definition of pT4 were coordinated by working group 3. It was agreed that prostate cancer can be categorized as pT3a in the absence of adipose tissue involvement when cancer bulges beyond the contour of the gland or beyond the condensed smooth muscle of the prostate at posterior and posterolateral sites. Extraprostatic extension can also be identified anteriorly. It was agreed that the location of extraprostatic extension should be reported. Although there was consensus that the amount of extraprostatic extension should be quantitated, there was no agreement as to which method of quantitation should be employed. There was overwhelming consensus that microscopic urinary bladder neck invasion by carcinoma should be reported as stage pT3a and that lymphovascular invasion by carcinoma should be reported. It is recommended that these elements are considered in the development of practice guidelines and in the daily practice of urological surgical pathology.

Protein intake and exercise for optimal muscle function with aging: recommendations from the ESPEN Expert Group.

The aging process is associated with gradual and progressive loss of muscle mass along with lowered strength and physical endurance. This condition, sarcopenia, has been widely observed with aging in sedentary adults. Regular aerobic and resistance exercise programs have been shown to counteract most aspects of sarcopenia. In addition, good nutrition, especially adequate protein and energy intake, can help limit and treat age-related declines in muscle mass, strength, and functional abilities. Protein nutrition in combination with exercise is considered optimal for maintaining muscle function. With the goal of providing recommendations for health care professionals to help older adults sustain muscle strength and function into older age, the European Society for Clinical Nutrition and Metabolism (ESPEN) hosted a Workshop on Protein Requirements in the Elderly, held in Dubrovnik on November 24 and 25, 2013. Based on the evidence presented and discussed, the following recommendations are made (a) for healthy older people, the diet should provide at least 1.0-1.2 g protein/kg body weight/day, (b) for older people who are malnourished or at risk of malnutrition because they have acute or chronic illness, the diet should provide 1.2-1.5 g protein/kg body weight/day, with even higher intake for individuals with severe illness or injury, and (c) daily physical activity or exercise (resistance training, aerobic exercise) should be undertaken by all older people, for as long as possible.

Repeat Gamma Knife surgery for recurrent trigeminal neuralgia: long-term outcomes and systematic review.

Object The purpose of this study was to establish the safety and efficacy of repeat Gamma Knife surgery (GKS) for recurrent trigeminal neuralgia (TN). Methods Using the prospective database of TN patients treated with GKS in Timone University Hospital (Marseille, France), data were analyzed for 737 patients undergoing GKS for TN Type 1 from July 1992 to November 2010. Among the 497 patients with initial pain cessation, 34.4% (157/456 with ≥ 1-year follow-up) experienced at least 1 recurrence. Thirteen patients (1.8%) were considered for a second GKS, proposed only if the patients had good and prolonged initial pain cessation after the first GKS, with no other treatment alternative at the moment of recurrence. As for the first GKS, a single 4-mm isocenter was positioned in the cisternal portion of the trigeminal nerve at a median distance of 7.6 mm (range 4-14 mm) anterior to the emergence of the nerve (retrogasserian target). A median maximum dose of 90 Gy (range 70-90 Gy) was delivered. Data for 9 patients with at least 1-year followup were analyzed. A systematic review of literature was also performed, and results are compared with those of the Marseille study. Results The median time to retreatment in the Marseille study was 72 months (range 12-125 months) and in the literature it was 17 months (range 3-146 months). In the Marseille study, the median follow-up period was 33.9 months (range 12-96 months), and 8 of 9 patients (88.9%) had initial pain cessation with a median of 6.5 days (range 1-180 days). The actuarial rate for new hypesthesia was 33.3% at 6 months and 50% at 1 year, which remained stable for 7 years. The actuarial probabilities of maintaining pain relief without medication at 6 months and 1 year were 100% and 75%, respectively, and remained stable for 7 years. The systematic review analyzed 20 peer-reviewed studies reporting outcomes for repeat GKS for recurrent TN, with a total of 626 patients. Both the selection of the cases for retreatment and the way of reporting outcomes vary widely among studies, with a median rate for initial pain cessation of 88% (range 60%-100%) and for new hypesthesia of 33% (range 11%-80%). Conclusions Results from the Marseille study raise the question of surgical alternatives after failed GKS for TN. The rates of initial pain cessation and recurrence seem comparable to, or even better than, those of the first GKS, according to different studies, but toxicity is much higher, both in the Marseille study and in the published data. Neither the Marseille study data nor literature data answer the 3 cardinal questions regarding repeat radiosurgery in recurrent TN: which patients to retreat, which target is optimal, and which dose to use.

Posterior cortical atrophy: review of the recent literature.

Posterior cortical atrophy (PCA) is a group of neurodegenerative dementing disorders characterized by initial predominant visual complaints followed by progressive decline in cognitive functions. The visuospatial and visuoperceptual defects arise from the dysfunction of, respectively, the dorsal (occipito-parietal) and the ventral (occipito-temporal) streams. Clinical symptoms, results of neuropsychological examination, and findings of posterior cerebral atrophy and/or posterior hypoperfusion/hypometabolism contribute to the diagnosis. However, owing to the insidious onset of PCA and the non-specificity of initial symptoms, the diagnosis is often delayed. Specific etiologies include Alzheimer's disease, dementia with Lewy bodies, subcortical gliosis, corticobasal degeneration, and prion-associated diseases. Alzheimer's disease accounts for at least 80 % of PCA cases. Recent research has concentrated on better defining the clinical presentation of PCA, improving neuroimaging analysis, testing new neuroimaging techniques, and developing biological measurements. Selected recent papers on PCA are reviewed in this article.

Strategies to promote translational research within the European Organisation for Research and Treatment of Cancer (EORTC) Head and Neck Cancer Group: a report from the Translational Research Subcommittee.

Head and neck squamous cell cancer (HNSCC) is the sixth leading cause of cancer-related deaths worldwide. These tumors are commonly diagnosed at advanced stages and mortality rates remain high. Even cured patients suffer the consequences of aggressive treatment that includes surgery, chemotherapy, and radiotherapy. In the past, in clinical trials, HNSCC was considered as a single disease entity. Advances in molecular biology with the development of genomic and proteomic approaches have demonstrated distinct prognostic HNSCC patient subsets beyond those defined by traditional clinical-pathological factors such as tumor subsite and stage [Cho W (ed). An Omics Perspective on Cancer Research. New York/Berlin: Springer 2010]. Validation of these biomarkers in large prospective clinical trials is required before their clinical implementation. To promote this research, the European Organisation for Research and Treatment of Cancer (EORTC) Head and Neck Cancer Program will develop the following strategies-(i) biobanking: prospective tissue collection from uniformly treated patients in the setting of clinical trials; (ii) a group of physicians, physician-scientists, and EORTC Headquarters staff devoted to patient-oriented head and neck cancer research; (iii) a collaboration between the basic scientists of the Translational Research Division interested in head and neck cancer research and the physicians of the Head and Neck Cancer Group; and (iv) funding through the EORTC Grant Program and the Network Core Institutions Consortium. In the present report, we summarize our strategic plans to promote head and neck cancer research within the EORTC framework.

Reduction in the proportion of fevers associated with Plasmodium falciparum parasitaemia in Africa: a systematic review.

BACKGROUND: Malaria is almost invariably ranked as the leading cause of morbidity and mortality in Africa. There is growing evidence of a decline in malaria transmission, morbidity and mortality over the last decades, especially so in East Africa. However, there is still doubt whether this decline is reflected in a reduction of the proportion of malaria among fevers. The objective of this systematic review was to estimate the change in the Proportion of Fevers associated with Plasmodium falciparum parasitaemia (PFPf) over the past 20 years in sub-Saharan Africa. METHODS: Search strategy. In December 2009, publications from the National Library of Medicine database were searched using the combination of 16 MeSH terms.Selection criteria. Inclusion criteria: studies 1) conducted in sub-Saharan Africa, 2) patients presenting with a syndrome of 'presumptive malaria', 3) numerators (number of parasitologically confirmed cases) and denominators (total number of presumptive malaria cases) available, 4) good quality microscopy.Data collection and analysis. The following variables were extracted: parasite presence/absence, total number of patients, age group, year, season, country and setting, clinical inclusion criteria. To assess the dynamic of PFPf over time, the median PFPf was compared between studies published in the years ≤2000 and > 2000. RESULTS: 39 studies conducted between 1986 and 2007 in 16 different African countries were included in the final analysis. When comparing data up to year 2000 (24 studies) with those afterwards (15 studies), there was a clear reduction in the median PFPf from 44% (IQR 31-58%; range 7-81%) to 22% (IQR 13-33%; range 2-77%). This dramatic decline is likely to reflect a true change since stratified analyses including explanatory variables were performed and median PFPfs were always lower after 2000 compared to before. CONCLUSIONS: There was a considerable reduction of the proportion of malaria among fevers over time in Africa. This decline provides evidence for the policy change from presumptive anti-malarial treatment of all children with fever to laboratory diagnosis and treatment upon result. This should insure appropriate care of non-malaria fevers and rationale use of anti-malarials.

Autologous Stem Cell Transplantation (ASCT) for Enteropathy-Associated T-Cell Lymphoma (EATL): Final Analysis of a Retrospective Study On the Behalf of Lymphoma Working Party (LWP) of the European Group for Blood and Marrow Transplantation (EBMT).

Background: EATL is a rare subtype of peripheral T-cell lymphomas characterized by primarily intestinal localization and a frequent association with celiac disease. The prognosis is considered to be poor with conventional chemotherapy. Limited data is available on the efficacy of ASCT in this lymphoma subtype. Primary objective: was to study the outcome of ASCT as a consolidation or salvage strategy for EATL. The primary endpoint was overall survival (OS) and progression-free survival (PFS). Eligible patients were > 18 years who had received ASCT between 2000-2010 for EATL that was confirmed by review of written histopathology reports, and had sufficient information on disease history and follow-up available. The search strategy used the EBMT database to identify patients potentially fulfilling the eligibility criteria. An additional questionnaire was sent to individual transplant centres to confirm histological diagnosis (histopathology report or pathology review) as well as updated follow-up data. Patients and transplant characteristics were compared between groups using X2 test or Fisher's exact test for categorical variables and t-test or Mann-Whiney U-test for continuous variables. OS and PFS were estimated using the Kaplan-Meier product-limit estimate and compared by the log-rank test. Estimates for non-relapse mortality (NRM) and relapse or progression were calculated using cumulative incidence rates to accommodate competing risk and compared to Gray's test. Results: Altogether 138 patients were identified. Updated follow-up data was received from 74 patients (54 %) and histology report from 54 patients (39 %). In ten patients the diagnosis of EATL could not be adequately verified. Thus the final analysis included 44. There were 24 males and 20 females with a median age of 56 (35-72) years at the time of transplant. Twenty-five patients (57 %) had a history of celiac disease. Disease stage was I in nine patients (21 %), II in 14 patients (33 %) and IV in 19 patients (45 %). Twenty-four patients (55 %) were in the first CR or PR at the time of transplant. BEAM was used as a high-dose regimen in 36 patients (82 %) and all patients received peripheral blood grafts. The median follow-up for survivors was 46 (2-108) months from ASCT. Three patients died early from transplant-related reasons translating into a 2-year non-relapse mortality of 7 %. Relapse incidence at 4 years after ASCT was 39 %, with no events occurring beyond 2.5 years after ASCT. PFS and OS were 54 % and 59 % at four years, respectively. There was a trend for better OS in patients transplanted in the first CR or PR compared to more advanced disease status (70 % vs. 43 %, p=0.053). Of note, patients with a history of celiac disease had superior PFS (70 % vs. 35 %, p=0.02) and OS (70 % vs. 45 %, p=0.052) whilst age, gender, disease stage, B-symptoms at diagnosis or high-dose regimen were not associated with OS or PFS. Conclusions: This study shows for the first time in a larger patient sample that ASCT is feasible in selected patients with EATL and can yield durable disease control in a significant proportion of the patients. Patients transplanted in first CR or PR appear to do better than those transplanted later. ASCT should be considered in EATL patients responding to initial therapy.

Reduction of alcohol consumption by brief alcohol intervention in primary care: systematic review and meta-analysis.

BACKGROUND: Numerous trials of the efficacy of brief alcohol intervention have been conducted in various settings among individuals with a wide range of alcohol disorders. Nevertheless, the efficacy of the intervention is likely to be influenced by the context. We evaluated the evidence of efficacy of brief alcohol interventions aimed at reducing long-term alcohol use and related harm in individuals attending primary care facilities but not seeking help for alcohol-related problems. METHODS: We selected randomized trials reporting at least 1 outcome related to alcohol consumption conducted in outpatients who were actively attending primary care centers or seeing providers. Data sources were the Cochrane Central Register of Controlled Trials, MEDLINE, PsycINFO, ISI Web of Science, ETOH database, and bibliographies of retrieved references and previous reviews. Study selection and data abstraction were performed independently and in duplicate. We assessed the validity of the studies and performed a meta-analysis of studies reporting alcohol consumption at 6 or 12 months of follow-up. RESULTS: We examined 19 trials that included 5639 individuals. Seventeen trials reported a measure of alcohol consumption, of which 8 reported a significant effect of intervention. The adjusted intention-to-treat analysis showed a mean pooled difference of -38 g of ethanol (approximately 4 drinks) per week (95% confidence interval, -51 to -24 g/wk) in favor of the brief alcohol intervention group. Evidence of other outcome measures was inconclusive. CONCLUSION: Focusing on patients in primary care, our systematic review and meta-analysis indicated that brief alcohol intervention is effective in reducing alcohol consumption at 6 and 12 months.

Impact of standardised review of intravenous antibiotic therapy 72 hours after prescription in two internal medicine wards.

Post-prescription review of hospital antibiotic therapy may contribute to more appropriate use. We estimated the impact of a standardised review of intravenous antibiotic therapy three days after prescription in two internal medicine wards of a university hospital. In one ward, we assessed the charts of patients under intravenous antibiotic therapy using a standardised review process and provided feedback to the prescriber. There was no intervention in the other ward. After six months we crossed the allocation between the two wards. In all, 204 courses of antibiotic therapy were included in the intervention periods and 226 in the control periods. Post-prescription review led to proposals for modification in 46% of antibiotic courses. Time to treatment modification was 22% shorter in the intervention periods compared with the control periods (3.9+/-5.2 days vs 5.0+/-6.0 days, P=0.007). Patients included in the intervention group had lower antibiotic consumption than patients in the control group, but the intervention had no significant impact on the overall antibiotic consumption of the two wards.

Pragmatic approach for interpreting antiretroviral drug concentrations based on a systematic review of population pharmacokinetic studies

Objectives: The study objective was to derive reference pharmacokinetic curves of antiretroviral drugs (ART) based on available population pharmacokinetic (Pop-PK) studies that can be used to optimize therapeutic drug monitoring guided dosage adjustment.¦Methods: A systematic search of Pop-PK studies of 8 ART in adults was performed in PubMed. To simulate reference PK curves, a summary of the PK parameters was obtained for each drug based on meta-analysis approach. Most models used one-compartment model, thus chosen as reference model. Models using bi-exponential disposition were simplified to one-compartment, since the first distribution phase was rapid and not determinant for the description of the terminal elimination phase, mostly relevant for this project. Different absorption were standardized for first-order absorption processes.¦Apparent clearance (CL), apparent volume of distribution of the terminal phase (Vz) and absorption rate constant (ka) and inter-individual variability were pooled into summary mean value, weighted by number of plasma levels; intra-individual variability was weighted by number of individuals in each study.¦Simulations based on summary PK parameters served to construct concentration PK percentiles (NONMEM®).¦Concordance between individual and summary parameters was assessed graphically using Forest-plots. To test robustness, difference in simulated curves based on published and summary parameters was calculated using efavirenz as probe drug.¦Results: CL was readily accessible from all studies. For studies with one-compartment, Vz was central volume of distribution; for two-compartment, Vz was CL/λz. ka was directly used or derived based on the mean absorption time (MAT) for more complicated absorption models, assuming MAT=1/ka.¦The value of CL for each drug was in excellent agreement throughout all Pop-PK models, suggesting that minimal concentration derived from summary models was adequately characterized. The comparison of the concentration vs. time profile for efavirenz between published and summary PK parameters revealed not more than 20% difference. Although our approach appears adequate for estimation of elimination phase, the simplification of absorption phase might lead to small bias shortly after drug intake.¦Conclusions: Simulated reference percentile curves based on such an approach represent a useful tool for interpretating drug concentrations. This Pop-PK meta-analysis approach should be further validated and could be extended to elaborate more sophisticated computerized tool for the Bayesian TDM of ART.

Surgery for Hirschsprung's disease: comparison between the Duhamel method and the transanal endorectal pull-through based on 59 patients and a review of the literature

Background:¦Hirschsprung's disease (HSCR) is a congenital malformation of the enteric nervous system due to the¦arrest of migration of neural crest cells to form the myenteric and submucosal plexuses. It leads to an anganglionic intestinal segment, which is permanently contracted causing intestinal obstruction. Its incidence is approximately 1/5000 birth, and males are more frequently affected with a male/female ratio of 4/1. The diagnosis is in most cases made within the first year of life. The rectal biopsy of the mucosa and sub-mucosa is the diagnostic gold standard.¦Purpose:¦The aim of this study was to compare two surgical approaches for HSCR, the Duhamel technique and the transanal endorectal pull-through (TEPT) in term of indications, duration of surgery, duration of hospital stay, postoperative treatment, complications, frequency of enterocolitis and functional outcomes.¦Methods:¦Fifty-nine patients were treated for HSCR by one of the two methods in our department of pediatric¦surgery between 1994 and 2010. These patients were separated into two groups (I: Duhamel, II: TEPT), which were compared on the basis of medical records. Statistics were made to compare the two groups (ANOVA test). The first group includes 43 patients and the second 16 patients. It is noteworthy that twenty-four patients (about 41% of all¦patients) were referred from abroad (Western Africa). Continence was evaluated with the Krickenbeck's score.¦Results:¦Statistically, this study showed that operation duration, hospital stay, postoperative fasting and duration of postoperative antibiotics were significantly shorter (p value < 0.05) in group II (TEPT). But age at operation and length of aganglionic segment showed no significant difference between the two groups. The continence follow-up showed generally good results (Krickenbeck's scores 1; 2.1; 3.1) in both groups with a slight tendency to constipation in group I and soiling in group II.¦Conclusion:¦We found two indications for the Duhamel method that are being referred from a country without¦careful postoperative surveillance and/or having a previous colostomy. Even if the Duhamel technique tends to be replaced by the TEPT, it remains the best operative approach for some selected patients. TEPT has also proved some advantages but must be followed carefully because, among other points, of the postoperative dilatations. Our postoperative standards, like digital rectal examination and anal dilatations seem to reduce the occurrence of complications like rectal spur and anal/anastomosis stenosis, respectively in the Duhamel method and the TEPT technique.

Molecular and clinical characterization of 25 individuals with exonic deletions of NRXN1 and comprehensive review of the literature.

This study aimed to elucidate the observed variable phenotypic expressivity associated with NRXN1 (Neurexin 1) haploinsufficiency by analyses of the largest cohort of patients with NRXN1 exonic deletions described to date and by comprehensively reviewing all comparable copy number variants in all disease cohorts that have been published in the peer reviewed literature (30 separate papers in all). Assessment of the clinical details in 25 previously undescribed individuals with NRXN1 exonic deletions demonstrated recurrent phenotypic features consisting of moderate to severe intellectual disability (91%), severe language delay (81%), autism spectrum disorder (65%), seizures (43%), and hypotonia (38%). These showed considerable overlap with previously reported NRXN1-deletion associated phenotypes in terms of both spectrum and frequency. However, we did not find evidence for an association between deletions involving the β-isoform of neurexin-1 and increased head size, as was recently published in four cases with a deletion involving the C-terminus of NRXN1. We identified additional rare copy number variants in 20% of cases. This study supports a pathogenic role for heterozygous exonic deletions of NRXN1 in neurodevelopmental disorders. The additional rare copy number variants identified may act as possible phenotypic modifiers as suggested in a recent digenic model of neurodevelopmental disorders. © 2013 Wiley Periodicals, Inc.

Using the costs of drug therapy to screen patients for a community pharmacy-based medication review program

Objectives: To measure the positive predictive value (PPV) of the cost of drug therapy (threshold = 2000 Swiss francs [CHF], US$1440, <euro>1360) as a screening criterion for identifying patients who may benefit from medication review (MR). To describe identified drug-related problems (DRPs) and expense problems (EPs), and to estimate potential savings if all recommendations were accepted. Setting Five voluntary Swiss community pharmacies. Methods: Of 12,680 patients, 592 (4.7%) had drug therapy costs exceeding 2000 CHF over a six-month period from July 1 to December 31, 2002. This threshold limit was set to identify high-risk patients for DRPs and EPs. Three pharmacists consecutively conducted a medication review based on the pharmaceutical charts of 125 sampled patients who met the inclusion criterion. Main outcome measure: The PPV of a threshold of 2000 CHF for identifying patients who might benefit from a MR: true positives were patients with at least one DRP, while false positives were patients with no DRP. Results: The selection based on this criterion had a PPV of 86% for detecting patients with at least one DRP and 95% if EPs were also considered. There was a mean of 2.64 (SD = 2.20) DRPs per patient and a mean of 2.14 (SD = 1.39) EPs per patient. Of these patients, 90% were over 65 years old or were treated with at least five chronic medications, two common criteria for identifying patients at risk of DRPs. The main types of DRPs were drug-drug interactions, compliance problems and duplicate drugs. Mean daily drug cost per patient was CHF 14.87 (US$10.70, <euro>10.10). A potential savings of CHF 1.67 (US$1.20, <euro>1.14) per day (11%) was estimated if all recommendations to solve DRPs and EPs suggested herein were implemented. Conclusion: Further studies should investigate whether the potential benefit of medication reviews in preventing DRPs and containing costs in this patient group can be confirmed in a real practice environment. [Authors]

Effectiveness of interventions targeting frequent users of emergency departments: a systematic review.

STUDY OBJECTIVE: Frequent users of emergency departments (EDs) are a relatively small group of vulnerable patients accounting for a disproportionally high number of ED visits. Our objective is to perform a systematic review of the type and effectiveness of interventions to reduce the number of ED visits by frequent users. METHODS: We searched MEDLINE, EMBASE, CINAHL, PsychINFO, the Cochrane Library, and ISI Web of Science for randomized controlled trials, nonrandomized controlled trials, interrupted time series, and controlled and noncontrolled before-and-after studies describing interventions targeting adult frequent users of EDs. Primary outcome of interest was the reduction in ED use. We also explored costs analyses and various clinical (alcohol and drug use, psychiatric symptoms, mortality) and social (homelessness, insurance status, social security support) outcomes. RESULTS: We included 11 studies (3 randomized controlled trials, 2 controlled and 6 noncontrolled before-and-after studies). Heterogeneity in both study designs and definitions of frequent users precluded meta-analyses of the results. The most studied intervention was case management (n=7). Only 1 of 3 randomized controlled trials showed a significant reduction in ED use compared with usual care. Six of the 8 before-and-after studies reported a significant reduction in ED use, and 1 study showed a significant increase. ED cost reductions were demonstrated in 3 studies. Social outcomes such as reduction of homelessness were favorable in 3 of 3 studies, and clinical outcomes trended toward positive results in 2 of 3 studies. CONCLUSION: Interventions targeting frequent users may reduce ED use. Case management, the most frequently described intervention, reduced ED costs and seemed to improve social and clinical outcomes. It appears to be beneficial to patients and justifiable for hospitals to implement case management for frequent users in the framework of a clear and consensual definition of frequent users and standardized outcome measures.