Recently we developed and validated generic quality indicators that define ‘appropriate antibiotic use’ in hospitalized adults treated for a (suspected) bacterial infection. Previous studies have shown that with appropriate antibiotic use a reduction of 13% of length of hospital stay can be achieved. Our main objective in this project is to provide hospitals with an antibiotic checklist based on these quality indicators, and to evaluate the introduction of this checklist in terms of (cost-) effectiveness.The checklist applies to hospitalized adults with a suspected bacterial infection for whom antibiotic therapy is initiated, at first via the intravenous route. A stepped wedge study design will be used, comparing outcomes before and after introduction of the checklist in nine hospitals in the Netherlands. At least 810 patients will be included in both the control and the intervention group. The primary endpoint is length of hospital stay. Secondary endpoints are appropriate antibiotic use measured by the quality indicators, admission to and duration of intensive care unit stay, readmission within 30 days, mortality, total antibiotic use, and costs associated with implementation and hospital stay. Differences in numerical endpoints between the two periods will be evaluated with mixed linear models; for dichotomous outcomes generalized estimating equation models will be used. A process evaluation will be performed to evaluate the professionals’ compliance with use of the checklist. The key question for the economic evaluation is whether the benefits of the checklist, which include reduced antibiotic use, reduced length of stay and associated costs, justify the costs associated with implementation activities as well as daily use of the checklist.If (cost-) effective, the AB-checklist will provide physicians with a tool to support appropriate antibiotic use in adult hospitalized patients who start with intravenous antibiotics.NTR4872Dutch trial registry:  The increasing antimicrobial resistance rate is one of the most important health care problems at this moment. The total consumption of antibiotics is the main driving force ,2. The WAbstract poster: Quality Indicators for Monitoring Appropriate Antibiotic Use in Hospitals: an Important Tool for Antibiotic Stewardship. K-325. 54th Interscience Conference on Antimicrobial Agents and Chemotherapy, September 5 -9, 2014, Washington DC].Previous studies have shown that appropriate antibiotic use is not only of great importance to curb antimicrobial resistance, but also has a short-term consequence. The evaluation of antibiotic treatment for urinary tract infections in hospitals showed an inverse relationship between the proportion of appropriate antibiotic use in a patient and length of stay (LOS). Prescribing therapy in accordance with local hospital guidelines was associated with a shorter LOS  . RecentlGuidelines defining appropriate antimicrobial treatment are available. To measure whether guideline recommendations are implemented in daily practice, an instrument is needed that validly measures the quality of antibiotic use in daily clinical practice. Guideline-based quality indicators (QIs) are such tools. Recently, generic QIs for the antimicrobial treatment of bacterial infections in hospitals have been developed and validated . The chaA checklist can be a tool for implementation; since it has been shown in other high-risk disciplines that adherence to checklists increases safety . This alWe hypothesize that an antibiotic checklist, to be used at the start of antibiotic treatment and after 48-72 hours of treatment, will improve clinical patient care, reduce costs and will ultimately contribute to the containment of antimicrobial resistance.This study is set to implement an antibiotic checklist based on the validated generic quality indicators measuring the appropriateness of intravenously initiated antibiotic use in hospitalized adults treated for a suspected bacterial infection, and to analyse the effect of the introduction of the checklist on patient care in terms of shorter duration of intensive care unit (ICU)- and hospital stay, adequate treatment, decreased mortality rates, decreased total antibiotic use and lower costs.The ‘Development of reliable generic quality indicators for the optimization of antibiotic use in the hospital’ (RIANT)-study used a RAND modified Delphi method to develop a set of generic QIs for appropriate antibiotic use in the treatment of all bacterial infections in hospitalized adult patients . The cliThe antibiotic checklist is intended as a reminding tool for the physician who starts intravenous (IV) antibiotic treatment. It is actually divided into two bundles Figure . The firAs a preparation, we identified barriers of implementing this checklist, using a questionnaire based on an instrument of the Netherlands Organization for Applied Scientific Research (TNO), which is designed to survey determinants that influence the uptake of an innovation in health care organizations ,13. The The (cost-) effectiveness of introducing the antibiotic checklist will be studied in a controlled, multicentre, prospective study using a stepped wedge design, comparing outcomes before and after implementation of the checklist while accounting for potential confounders .The checklist will be introduced in nine hospitals over four time periods, during a total study period of eleven months Figure . The aimTo promote selection of a patient population representative for every day clinical practice in the Netherlands, two university hospitals and seven teaching hospitals will participate, and in each hospital at least one surgical and one non-surgical ward will be included. The ICU and the paediatric ward will be excluded, as the quality indicators do not apply to these populations. Patients with a suspected bacterial infection presenting on the emergency department (ED) will be included if they are going to be hospitalized on one of the participating wards.The study coordinator will design a project plan together with the local project leader. This plan will focus on physicians, nurses and medical students who are involved in patient care. The plan will include standard items , or adults at the ED who will be admitted at a participating ward, with a suspected community-acquired and/or hospital-acquired bacterial infection, and will be treated with intravenous antibiotics. The treating physician identifies these patients upon prescription of antibiotic therapy. The patients included in the study are all patients that meet the above mentioned inclusion criteria, whether they have a completed checklist or not  , admissiFor patient outcome we will collect data concerning the LOS, admission to and duration of ICU stay, readmission within 30 days and mortality in hospital or within 30 days after discharge for the baseline group and the intervention group. Furthermore we will collect data for possible confounders of patient’s outcome, namely age, sex, community-or hospital acquired infection, Charlson comorbidity index ,16, use Antibiotics included in the study belong to group J01  of the Anatomic Therapeutic Chemical (ATC) classification system. When multiple antibiotics are prescribed to one patient, all antibiotics will be registered. Antiviral therapy, medication for tuberculosis, antibiotics used for non-systemic selective intestinal decontamination and antibiotics used as pro-kinetics will be excluded.The power analysis is based on previous results of appropriate antibiotic use on length of stay as described at ‘background’ ,7. In a We will use mixed linear models to analyse the overall effect of the introduction of the checklist on length of stay. Therefore we will evaluate differences between baseline (before introduction of the checklist) and intervention plus spill over (after introduction of the checklist) . We will also determine the theoretical effect of the checklist on LOS by evaluating differences between baseline and intervention data without the spill over data . Differences between the baseline data and the intervention data for secondary outcomes will also be evaluated with mixed linear models. For dichotomous outcomes , the comparison will be evaluated with a similar approach, using generalized estimating equation models. These mixed models account for within-cluster dependencies, and allow adjustment for possible confounders. To assess whether differences between these groups may be explained by confounding patient characteristics, we will first test with multivariate multilevel (linear mixed) analyses if these variables have a significant effect (p < 0.05) on the outcomes. Hereafter, we will compute the estimate of the total causal effect of checklist implementation on the outcomes before and after adjusting for a significant variable. If the estimate varies 10% or more, possible confounding is present and in that case we will adjust for this variable.We will evaluate the physicians’ compliance with the checklist. Firstly we will check whether the ticks in the completed checklists are in accordance with the performance in clinical practice. Secondly we will determine the percentage of eligible patients for whom the checklist has been used after checklist introduction. The number of patients in whom the checklist was actually used (the intervention group) will be divided by the number of patients in whom it should have been used (the intervention plus the spill over group).The key question for the economic evaluation is whether the benefits of using the checklist, which will likely include reduced antibiotic use, reduced length of stay and associated costs, justify the costs associated with implementation activities as well as daily use of the checklist. For reasons of feasibility, the cost analysis will only include a few main cost drivers of health care utilization, namely LOS on a general or ICU ward and antibiotic use. Unit costs for health care utilization will be estimated according to the Dutch guideline on (unit) costing in health care . LOS andThe project proposal was discussed with the Medical Ethics Research Committee of the Academic Medical Centre. They confirmed that the Medical Research Involving Human Subjects Acts does not apply to this study and that an official approval by the committee was not required, because patients will receive treatment according to standard care, and will have no burden of checklist use.http://apps.who.int/trialsearch/) investigate the implementation of a generic antibiotic checklist to be used for suspected bacterial infections in the hospital. If (cost) effective, the AB-checklist will provide physicians with a tool to support appropriate antibiotic use in adult hospitalized patients who start intravenous antimicrobials.This study protocol describes the design, implementation and evaluation of the AB-checklist study. To our knowledge, no other published studies or ongoing trials (


Many studies about serum IgG4 for the diagnosis of IgG4-related disease (IgG4-RD) have been reported. However, these studies had relatively small sample sizes and the diagnostic accuracy values varied much between them.The aim of this study was to perform a meta-analysis to evaluate the diagnostic value of serum IgG4 for IgG4-RD.We conducted a search of relevant articles using MEDLINE, EMBASE, Web of Science, SCOPUS, and Cochrane Library databases published before December 2015.Studies those assessed the diagnostic accuracy of serum IgG4 for IgG4-RD and those provided the cut-off value for serum IgG4 were included.Data were synthesized using the random-effect model. Statistical analysis was performed using STATA with the MIDAS module and Meta-DiSc 1.4 software.A total of 9 case-control studies were analyzed, which included 1235 patients with IgG4-RD and 5696 overall controls. The pooled estimate, for a cut-off value ranged from 135 to 144 mg/dL, produced a sensitivity of 87.2%  and a specificity of 82.6% . The positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were 6.48 , 0.14 , and 45.15 , respectively. The area under the curve (AUC) of the summary receiver operating characteristic curve (SROC) was 0.94 (0.92–0.96). When a cut-off value of 2-fold the upper limit of normal was used (ranged from 270 to 280 mg/dL), the pooled sensitivity was 63% , and the specificity was 94.8% . The PLR, NLR, and DOR were 13.3 , 0.41  and 33.42 , respectively. The AUC of the SROC was 0.92 (0.90–0.94).Only a relatively small number of studies were included, and significant heterogeneity was observed in this meta-analysis.Serum IgG4 is a modestly effective marker to diagnose IgG4-RD. Doubling the cut-off value for IgG4 could not improve the overall test characteristics. A high specificity inevitably accompanies with a significant sacrifice in sensitivity. The comprehensive diagnostic criteria for IgG4-RD contained 3 major criteria: (1) clinical characteristics of diffuse/localized swelling or masses in single or multiple organs; (2) serum IgG4 concentrations ≥135 mg/dL; (3) histopathologic characteristics of marked lymphocyte and plasmacyte infiltration and fibrosis, infiltration of IgG4-positive plasma cells: >40% of IgG4/IgG positive plasma cells and >10 IgG4 positive cells/high powered field of biopsy sample.15 Some previous meta-analysis studies focused on autoimmune pancreatitis (AIP)-the typical IgG4-RD.17 But these AIP patients were not clearly described to be with type-1 or type-2 AIP. In order to better know the diagnosis accuracy associated with serum IgG4 concentration for the diagnosis of IgG4-RD, we reviewed the current evidence to perform this meta-analysis and systematic review.So far, a wide range of diagnostic accuracy values of serum IgG4 for the diagnosis of IgG4-RD have been reported, and these studies have had relatively small sample sizes.We searched MEDLINE, EMBASE, Web of Science, SCOPUS, and Cochrane Library from inception to December 2015. We used the terms “IgG4-related disease” OR “IgG4-related diseases” as text words combined with “serum IgG4” OR “serum immunoglobulin g4.” We also contacted the corresponding authors by e-mail for those unpublished data of some literatures. Studies were excluded if no response was received. All analyses of this systemic review were based on previous published studies, so no ethical approval and patient consent are required.Studies meeting the following criteria were eligible for inclusion: those that assessed the diagnostic accuracy of serum IgG4 for IgG4-RD; those providing detailed diagnostic criteria of IgG4-RD; sufficient data reported to construct a two-by-two table; studies providing the cut-off value for serum IgG4; no language restrictions. The exclusion criteria were: animals, cell cultures, reviews or case reports; duplicate articles; not original articles; <10 IgG4-RD patients or disease controls; insufficient data to construct a two-by-two table; studies focused on AIP which were not clearly described to be type-1 or type-2 were also excluded.18 Summary of QUADAS-2 plot was generated by the Review Manager Software .The following data were extracted from the included studies: first author; published year; geographical region; disease names and main control diseases; detection method; cut-off value; diagnostic criteria of IgG4-RD; sample size; true positive (TP); false positive (FP); false negative (FN); and true negative (TN). According to the media of sample size, eligible studies were classified as large (≥ median sample size) or small (< median sample size). The accuracy of the data was verified by a second investigator (Liu). Discrepancies between 2 reviewers were resolved by consensus after discussion. The quality of each study was assessed according to the QUADAS-2  by 2 investigators.The pooled sensitivity, specificity, PLR, NLR, DOR, and their confidence intervals (95% CIs) were calculated by the accuracy data  extracted from each eligible study. The SROC was generated, and the AUC was calculated to represent the overall performance of the detection method.P value < 0.05 indicated a significant threshold effect. The heterogeneity across included studies caused by the nonthreshold effect was examined by Cochrane Q-statistic and I2 tests. The I2 test was used to estimate the extent of heterogeneity. A I2 value >30% would indicate moderate heterogeneity and a value >50% would represent substantial heterogeneity.19 Possible sources of heterogeneity and their effects on the results were explored by subgroup analyses and sensitivity analyses. Prespecified subgroup analyses stratified by sample size, regions, diseases were performed to assess the influence of the above parameters. Deeks’ funnel plot was performed to detect the publication bias. A P value <0.10 indicated significant publication bias.Spearman rank correlation was used to test for threshold effects, and a P values were 2 sided and P<0.05 was considered to be statistically significant.Statistical analysis was performed using the STATA software  with the MIDAS module and Meta-DiSc 1.4 . All reported A total of 1514 records were retrieved from initial search on electronic databases, with 321 from EMBASE, 304 from PUBMED, 640 from SCOPUS, 247 from Web of Science, and 2 from the reference lists by hand research. In total, 504 records were removed after duplicates by computer. After title and abstract screening, 993 articles were excluded. Overall, 17 full texts were examined for the eligibility of inclusion. Also, 8 articles were further excluded because they were duplicates, review articles, or insufficient data to construct a two-by-two table. Finally, 9 case-control studies met the inclusion criteria  and an average specificity of 82.6% . Additionally, the average PLR and NLR were 6.48  and 0.14 , respectively. The DOR was 45.15 . The AUC of the SROC was 0.94 (0.92–0.96). The sensitivity and specificity forest plots and SROC curve were shown in Figure All the 9 analyzed studies provided a cut-off value of the upper limit of normal between 135 and 144 mg/dL. The reported sensitivity of the serum IgG4 for the diagnosis of IgG4-RD ranged from 71.1% to 100%, and the reported specificity ranged from 59.4% to 96.6%. The pooled estimate, by using a random-effects model, produced an average sensitivity of 87.2%  and an average specificity of 94.8% . Additionally, the average PLR and NLR were 13.3  and 0.41 , respectively. The DOR was 33.42  and AUC of the SROC was 0.92 (0.90–0.94). The forest plots and SROC were shown in Figure In total, 6 of 9 studies in our meta-analysis provided the diagnostic values of 2-fold the upper limit of normal between 270 and 280 mg/dL. These studies included a total of 989 patients with IgG4-RD and 4404 overall controls. The reported sensitivity of the serum IgG4 for diagnosis of IgG4-RD ranged from 34.7% to 75.2%, and the reported specificity ranged from 90.9% to 98.4%. The pooled estimate, by using a random-effects model, produced an average sensitivity of 63%  and –0.486 (P = 0.329) for the 2 cut-offs of serum IgG4, respectively, which suggested the absence of threshold effect. Considering the significant heterogeneity among studies, we performed subgroup analyses to explore the source of heterogeneity. Sample size, regions, and diseases were analyzed for each accuracy data. However, none of these above was identified as a possible source of heterogeneity. Nevertheless, the diagnostic accuracy data were consistent across different subgroups , but the sensitivity was lower (63%). The pooled DOR was 33.42 and the AUC of SROC was 92.17, which were not improved in comparison with the conventional cut-off value. The higher specificity derived from the higher cut-off value for serum IgG4 concentration, however, came at a significant reduction in sensitivity.15 The other study by Carruthers et al7 showed neither the specificity nor the positive predictive value was improved by the serum IgG4/IgG ratio for the diagnosis of IgG4-RD. These finding supported that the IgG4/IgG ratio could not improve the overall test characteristics compared with serum IgG4 alone. To better elucidate the usefulness of serum IgG4/IgG ratio, further studies are needed.In addition, 2 of the enrolled studies investigated the diagnostic value of serum IgG4 with total serum IgG (IgG4/IgG) ratios for IgG4-RD. One found that the ROC curve of serum IgG4/IgG ratio was almost identical to the serum IgG4 concentration.Substantial heterogeneity in the pooled accuracy data was found among studies. Subgroup analysis was performed according to sample size, regions, and diseases. But unfortunately, none of the analyzed covariates was the source of heterogeneity. We also performed sensitivity analyses and found that the pooled results were relatively stable and not affected by a single study. As we know, IgG4-RD is a systematical disorder involving numerous organs including the pancreas, salivary glands, retroperitoneum, kidneys, lymph nodes, and others. Additionally, different case controls were enrolled according to the purposes and the interested diseases. The heterogeneity could possibly be caused by difference in selection of IgG4-RD cases and controls.21 Only type 1 AIP is part of the spectrum of IgG4-RD. In a previous meta-analysis, Morselli-Labate and Pezzilli16 reported the pooled sensitivity and specificity of serum IgG4 in diagnosing AIP were 82.4% and 94.6%, respectively.16 Similar findings were reported in a recent study by Lian et al.17 The results indicated that serum IgG4 exhibited high specificity (94%) and relatively low sensitivity (74%). However, the subtypes of these AIP patients in the included studies were not clearly described, which might explain the difference to our findings. Furthermore, although no publishing years were set during our literature searching, only publications after 2011 were included in this meta-analysis. This was consistent with that the newly emerged disease was referred to as IgG4-RD only more than a decade ago.22 More detailed diagnostic criteria were proposed which can ensure the selection of patients with IgG4-RD and overall controls.Our findings were strengthened by excluding the studies concerning the diagnostic value of serum IgG4 for AIP, in which the subtypes of AIP patients were not clearly described. AIP could be classified into 2 types according to the international consensus diagnostic criteria (ICDC).Several limitations in this meta-analysis need to be acknowledged. First, only a relatively small number of studies with limited subjects were included in the meta-analysis, which may reduce the statistical power for determining the diagnostic role of serum IgG4. Second, as mentioned above, significant heterogeneity was observed in this analysis. Because the number of included studies was <10, a multivariate meta-regression was not performed. New studies should be specifically designed in order to identify the possible confounding factors.In conclusion, this study is the first to assess the diagnostic accuracy of serum IgG4 in patients with IgG4-RD using meta-analysis, which provided evidence that serum IgG4 is a modestly effective marker for the disease. Doubling the cut-off value for IgG4 could improve the specificity, but inevitably accompany with a significant sacrifice in sensitivity.


The aim of this study was to clarify the effectiveness of various imaging modalities and characteristic imaging features in the screening of IgG4-related dacryoadenitis and sialadenitis (IgG4-DS), and to show the differences in the imaging features between IgG4-DS and Sjögren’s syndrome (SS).18F]-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT), computed tomography (CT) and magnetic resonance imaging (MRI) were retrospectively analyzed. Six oral and maxillofacial radiologists randomly reviewed the arranged image sets under blinded conditions. Each observer scored the confidence rating regarding the presence of the characteristic imaging findings using a 5-grade rating system. After scoring various findings, diagnosis was made as normal, IgG4-DS or SS, considering all findings for each case.Thirty-nine patients with IgG4-DS, 51 with SS and 36 with normal salivary glands were enrolled. Images of the parotid and submandibular glands obtained using sonography, 2-[18F-FDG accumulation and swelling of both the parotid and submandibular glands in patients with IgG4-DS, particularly in the submandibular glands. On MRI, SS had a high score regarding the findings of a salt-and-pepper appearance and/or multiple cystic areas in the parotid glands (median score 4.5). Sonography showed the highest values among the four imaging modalities for sensitivity, specificity and accuracy. There were significant differences between sonography and CT (p = 0.0001) and between sonography and FDG-PET/CT (p = 0.0058) concerning accuracy.On sonography, multiple hypoechoic areas and hyperechoic lines and/or spots in the parotid glands and obscuration of submandibular gland configuration were detected mainly in patients with SS . Reticular and nodal patterns were observed primarily in patients with IgG4-DS (median score 5). FDG-PET/CT revealed a tendency for abnormal 18F-FDG accumulation). Even inexperienced observers could detect these findings. In addition, sonography could also differentiate SS. Consequently, we recommend sonography as a modality for the screening of IgG4-DS, because it is easy to use, involves no radiation exposure and is an effective imaging modality.Changes in the submandibular glands affected by IgG4-DS could be easily detected using sonography  and FDG-PET/CT (abnormal  Immunoglobulin G4 (IgG4)-related dacryoadenitis and sialadenitis (IgG4-DS), Mikulicz’s disease, has recently been recognized as being an independent entity from Sjögren’s syndrome (SS), because of its clinical and serological features –3. Yamam67Ga scintigraphy; two on 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT); three on sonography; and two on computed tomography (CT) and magnetic resonance imaging (MRI). Ishii et al. analyzed 13 cases with IgG4-related disease (IgG4-RD) including IgG4-DS using 67Ga scintigraphy, and showed that there was significant accumulation in the lacrimal glands in seven cases and in the salivary glands in seven cases [67Ga between 27 cases of sarcoidosis and 16 cases of IgG4-RD [18F-FDG uptake in sites involved with IgG4-RD [Regarding imaging diagnosis of IgG4-DS, most of the studies have been case reports, and we could only find a few which analyzed the effectiveness of the imaging modality involving ≥9 cases as follows: two studies on en cases . In anotwo on 2-1F-fluoro- IgG4-RD . Sonogra IgG4-RD . In cont IgG4-RD , 13; alt IgG4-RD . BecauseThe purposes of the present retrospective study were to analyze the imaging features of IgG4-DS using various imaging modalities, and to clarify which imaging modality is the most effective for screening this disease. We also showed the differences in imaging characteristics between IgG4-DS and SS.We enrolled 39 patients with IgG4-DS  with a mean age of 59.9 years, between 1999 and 2014. IgG4-DS was serologically and histopathologically confirmed using the following diagnostic criteria: persistent symmetrical swelling involving >2 lacrimal and major salivary glands; an elevated serum level of IgG4 (>135 mg/dl); and infiltration of IgG4-positive plasma cells (percentage of IgG4-positive cells to IgG-positive cells >40 %) on immunostaining . We alsoWe performed sonography on 30 patients with IgG4-DS, 38 with SS and 36 with normal salivary glands. Sonographic images were taken using a diagnostic unit  with a center frequency of 12 megahertz (MHz). We extracted B-mode longitudinal images of both the parotid glands  and the submandibular glands  for this study. Because insufficient Doppler images could be provided for the normal submandibular glands, we only used B-mode images, although we also recorded in the Doppler mode at the time of examination for IgG4-DS and SS. FDG-PET/CT was undertaken in 20 patients with IgG4-DS, 19 with SS and 21 with normal salivary glands. From the superimposed images, where the standardized uptake value (SUV) was reflected as graded colors, we extracted images at the parotid and submandibular gland level, not including the lacrimal gland level. Similarly, CT images at the parotid and submandibular gland level of 24, 38 and 32 patients with IgG4-DS, SS and normal salivary glands, respectively and MRI of 5, 16 and 19 patients with IgG4-DS, SS and normal salivary glands, respectively, were also extracted for this study. Regarding MRI, besides plain axial T1- and T2-weighted images, we also extracted gadolinium-enhanced T1-weighted images and coronal images of parotid and/or submandibular glands (if any were present). We did not include images of the lacrimal glands. The reasons for this were: 1) we could not undertake sonography of the lacrimal glands for safety reasons regarding the eyes; and 2) when salivary gland tumors were suspected in the patients, lacrimal glands were often not included in the scanning range on CT/MRI.Six oral and maxillofacial radiologists (with 2–26 years of diagnostic experience) randomly reviewed the arranged image sets under blinded conditions. The observation order involved sets of: 1) sonographic images; 2) FDG-PET/CT images; 3) CT images; and 4) MRI images. Observations were performed twice with a 3-week interval. Each observer was required to score the confidence rate for the presence of the characteristic imaging findings using a 5-grade rating system (1–5) in the answer sheet as follows: when written characteristic imaging findings were definitely present, 5; when written characteristic imaging findings were definitely absent, 1; presence of a swollen gland, 5; and presence of an atrophied gland, 1. After scoring each finding, diagnosis was made as normal, IgG4-DS or SS, taking into consideration all of the findings for each case.Figure 18F-FDG accumulation in the parotid and submandibular glands was assessed as one of the characteristic findings of IgG4-DS [On FDG-PET/CT, abnormal  IgG4-DS , 8  were assessed with kappa values using 3 grades: 1 or 2, 3, and 4 or 5. Values <0.20 indicated poor agreement, 0.21–0.40 fair agreement, 0.41–0.60 moderate agreement, 0.61–0.80 good agreement and 0.81–1.00 excellent agreement.We calculated the sensitivity, specificity and accuracy using the following equations: sensitivity for IgG4-DS = a/(a+d+g), sensitivity for SS = e/(b+e+h), specificity = i/(c+f+i), accuracy = (a+e+i)/(a+b+c+d+e+f+g+h+i), where a: number of patients we diagnosed with IgG4-DS and who actually had IgG4-DS, b: number of patients we diagnosed with IgG4-DS but who had SS, c: number of patients we diagnosed with IgG4-DS but who were normal, d: number of patients we diagnosed with SS but who had IgG4-DS, e: number of patients we diagnosed with SS and who actually had SS, f: number of patients we diagnosed with SS but who were normal, g: number of patients we diagnosed as normal but who had IgG4-DS, h: number of patients we diagnosed as normal but who had SS, and i: number of patients we diagnosed as normal and who were actually normal. We performed the Bartlett test for the analysis of equal variance. To determine whether or not there were significant differences between two given groups among three, we performed the Steel-Dwass test in case of unequal variance, and the Tukey-Kramer test in case of equal variance using the statistical software JMP Pro 11.0 . Intra-observer agreement rates between the repeat diagnoses were very high. Kappa values for selecting the same diagnosis from normal, IgG4-DS or SS were 0.83  on sonography, 0.69  on FDG-PET/CT, 0.70  on CT and 0.80  on MRI. Moreover, average kappa values for each finding were 0.62 for sonography, 0.61 for FDG-PET/CT, 0.51 for CT and 0.54 for MRI; no findings showed an inverted order of scores the second time. Therefore, we have shown the results of the first diagnosis in the relevant figures.p ≤0.0093) were observed between any two of the three diagnoses. The parotid glands of patients with SS mainly exhibited multiple hypoechoic areas (median score 4) and hyperechoic lines and/or spots (median score 4)  were seen between the two  Fig.  and b, w 4) Fig. . In the two Fig.  and e. Otwo Fig. . In conttwo Fig.  and h. IEach case was diagnosed as normal, IgG4-DS or SS based on all of the sonographic findings. Sonographic sensitivity for detection of IgG4-DS and of SS, specificity and accuracy were 0.85, 0.80, 0.84 and 0.83, respectively.18F-FDG and swelling of both the parotid  and submandibular glands   , and between patients with IgG4-DS and those with normal glands (p <0.0001); however, this was not seen between patients with normal glands and SS (p = 0.1180). Intra-observer agreement rates between the repeat diagnoses were high . Regarding all other findings, significant differences (p ≤0.0049) were observed between any two of three diagnoses.FDG-PET/CT involving patients with IgG4-DS showed a tendency for abnormal accumulation of ly) Fig. . SeparatSS) Fig. . In relaEach case was diagnosed as normal, IgG4-DS or SS based on all of the findings from FDG-PET/CT. The sensitivity for detection of IgG4-DS and of SS, specificity and accuracy using FDG-PET/CT were 0.79, 0.59, 0.81 and 0.73, respectively.p = 0.0255; submandibular glands, median score 3, p <0.0001), there seemed to be a similar tendency between these two. Conversely, patients with SS had small parotid (median score 3) and submandibular glands (median score 2), especially submandibular glands. Patients with SS had a high score regarding the finding of a salt-and-pepper appearance and/or dot-like calcification (median score 4) , although this was not the case for between patients with normal glands and IgG4-DS (p = 0.7945). Superficial enhancement of the parotid glands (median score 2 for IgG4-DS) ; however, overlap was also observed and separation was not so good.Figure  4) Fig. . RegardiDS) Fig.  and the DS) Fig. , which wEach case was diagnosed as normal, IgG4-DS or SS based on all of the findings from CT. The sensitivity for detection of IgG4-DS and of SS, specificity and accuracy by CT were 0.64, 0.73, 0.70 and 0.70, respectively.p <0.0001). Conversely, patients with SS had small parotid (median score 3) and submandibular glands (median score 2), especially submandibular glands; there was a very clear separation between the other two conditions. Patients with SS had a high score regarding the finding of a salt-and-pepper appearance and/or multiple cystic areas in the parotid glands (median score 4.5) , although a significant difference was not seen between patients with normal glands and IgG4-DS (p = 0.4163). Fatty degeneration in the parotid glands, which we considered to be one of the characteristic findings of SS, showed significant differences between the other two conditions (p <=0.0061); however, overlap was also observed and separation was not so good.Figure .5) Fig. ; there wEach case was diagnosed as normal, IgG4-DS or SS based on all of the findings. The sensitivity for detection of IgG4-DS and of SS, specificity and accuracy using MRI were 0.80, 0.67, 0.81 and 0.76, respectively.p <0.001). Concerning the sensitivity of SS, there were significant differences between sonography and FDG-PET/CT (p = 0.0004) and between CT and FDG-PET/CT (p = 0.0180). In relation to specificity, there were significant differences between sonography and CT (p = 0.0463). Regarding the accuracy, there were significant differences between sonography and CT (p = 0.0001) and between sonography and FDG-PET/CT (p = 0.0058); however, there were no significant differences between sonography and MRI (p = 0.0796).Figure 18F-FDG in the submandibular glands on FDG-PET/CT were very effective. However, the effective findings regarding the screening of SS were a salt-and-pepper appearance and/or multiple cystic areas in the parotid glands on MRI. Taking into consideration high sensitivity for both IgG4-DS and SS, and high specificity in addition to high accuracy, the most effective imaging modality was sonography.For screening IgG4-DS, the nodal pattern of the submandibular glands on sonograms and the abnormal accumulation of 18F-FDG accumulation on FDG-PET/CT, and as abnormal swelling on CT and MRI. Consequently, the abnormal findings of images of the lacrimal glands would raise the accuracy of all modalities equally, and the effectiveness of each modality would not change appreciably.We did not include images of the lacrimal glands. Even if they were included, we could detect the affected lacrimal glands as a nodal pattern on sonograms, as abnormal Sonography provided useful information regarding the screening of IgG4-DS. The nodal and reticular patterns, often with normal parenchyma surrounding the affected region and located bilaterally, were easily detected in the submandibular glands even by inexperienced observers. When the sublingual glands are affected, they also show a nodal and/or reticular pattern on sonograms (data not shown); therefore, it would be easier to make an accurate diagnosis. Using sonography, not only IgG4-DS but also SS can be detected. Multiple hypoechoic areas and hyperechoic lines and/or spots in the parotid glands achieved high scores. These findings might be misleading, because IgG4-DS sometimes exhibits similar findings. However, hypoechoic areas of IgG4-DS were observed in the normal parotid parenchyma without a reduction in the echo intensity level and heterogeneity. Moreover, IgG4-DS mainly affects the submandibular glands, and most of the cases present with normal parotid glands . Convers18F-FDG accumulation in the glands affected with IgG4-DS. However, this imaging modality could not differentiate between normal glands and SS. Patients with SS do not undergo FDG-PET/CT, unless they have other malignant diseases. Our cases involving FDG-PET/CT were patients with SS who were partly suspected of having malignant lymphoma. When patients actually had lymphoma, the SUV was high and we could not differentiate the disease from IgG4-DS. Conversely, very severe SS with atrophic submandibular glands exhibited a very low SUV both in the parotid and submandibular glands. In contrast, SS patients in the lower stages  had a rather high SUV . This finding was in accordance with a report by Cohen et al. [18F-FDG uptake in the salivary glands is variable [FDG-PET/CT showed abnormal n et al. . Normal variable , we needNodal changes in IgG4-DS detected using sonography were not clearly observed on CT or MRI. In some cases CT and MRI displayed superficial enhancement in the parotid glands of IgG4-DS. However, unspecific swelling of the parotid and submandibular glands was observed in general. Most of the patients with normal salivary glands, that were large in size, were misdiagnosed as IgG4-DS. Some of our cases showed slightly low signal intensity on T2-weighted images on MRI; however, they were not significant. These results were not in accordance with the very low signal intensity on T2-weighted images , 13. ThiTwo things are important in diagnosing IgG4-DS. The first is to differentiate malignant lymphoma. Malignant lymphoma sometimes affects salivary glands, and can appear in bilateral glands, which mimic IgG4-DS . To make18F-FDG accumulation. Even inexperienced observers could detect these findings. In addition to IgG4-DS, sonography could also differentiate SS. Therefore, we recommend sonography as a modality for the screening of IgG4-DS, because it is easy to use, does not involve radiation exposure and is an effective imaging modality.Changes in the submandibular glands affected by IgG4-DS, which often occur bilaterally, could be easily detected using sonography as a result of characteristic bilateral nodal/reticular changes and by FDG-PET/CT because of abnormal


Elevated serum IgG4 levels are an important hallmark for diagnosing IgG4-related disease (IgG4-RD), but can also be observed in other diseases. This study aimed to compare two different testing methods for IgG4: ELISA and nephelometric assay. Both assays were used to measure serum IgG4 concentrations, and to assess the prevalence of high serum IgG4 levels in both IgG4-RD and non-IgG4-RD diseases.A total of 80 serum samples were tested using the nephelometric assay and ELISA method that we established. Serum IgG4 concentrations were determined by ELISA for 957 patients with distinct diseases, including 12 cases of IgG4-RD and 945 cases of non-IgG4-RD.IgG4 levels from 80 selected serum samples examined by ELISA were in agreement with those detected using the nephelometry assay. Meanwhile, the serum IgG4 concentrations measured by ELISA were also consistent with the clinical diagnoses of patients with IgG4-RD during the course of disease. The Elevated levels of serum IgG4 (>1.35 g/L) were detected in all IgG4-RD (12/12) patients, and the prevalence of high IgG4 serum levels was 3.39% in non-IgG4-RD cases. Among them, the positive rates of serum IgG4 were 2.06% in patients with carcinoma and 6.3% in patients with other non-IgG4 autoimmune diseases.Our established ELISA method is a reliable and convenient technique, which could be extensively used in the clinic to measure serum IgG4 levels. High levels of IgG4 were observed in IgG4-RD. However, this phenomenon could also be observed in other diseases, such as carcinomas and other autoimmune diseases. Thus, a diagnosis of IgG4 disease cannot only be dependent on the detection of elevated serum IgG4 levels. IgG4-related disease (IgG4-RD) is an idiopathic, fibroinflammatory clinicopathological entity characterized by elevated serum IgG4 levels, tumefaction, and abundant lymphoplasmacytic infiltration of IgG4-positive plasma cells in involved tissues , with a +/IgG+ plasmacytes >40% and IgG4-positive plasmacytes >10 per high power field (HPF) in involved tissues contribute to the diagnosis of IgG4-RD [A serum cutoff value of IgG4 levels >1.35 g/L has become widely accepted for the diagnosis of the IgG4-RD [ IgG4-RD , Castlem IgG4-RD , Churg-S IgG4-RD , althougIn this study, to validate the effectiveness of our newly established ELISA method, we compared the results conducted by ELISA method and nephelometric assay, and also observed whether high levels of serum IgG4 could be determined in other disorders. We collected 957 serum samples to screen IgG4 concentrations using our newly established ELISA technique. Meanwhile,80 of 957 samples were screened using the nephelometric assay.957 serum samples were collected from patients at Tongji Hospital at Huazhong University of Science and Technology,including cases of IgG4-RD(n = 12), connective diseases(n = 127),nephropathy(n = 36),digestive diseases(n = 60),hematological diseases(n = 38),infectious diseases(n = 18), cardiovascular diseases (n = 25),neurological disorders(n = 24), gynecopathy(n = 11),respiratory disorders (n = 24), carcinoma (n = 535), and other disorders, such as diabetes mellitus, ophthalmopathy, and traumatism (n = 47). There were 12 patients who were eventually diagnosed as IgG4-RD, in accordance with the IgG4-RD diagnostic criteria [The assays for serum IgG4 detection were performed from March 12, 2013 to July 1, 2014 at the rheumatic laboratory of Tongji hospital, Huazhong University of Science and Technology using our previously established ELISA method . All ELIStatistical analysis was performed using SPSS version 17.0 statistical analysis software . Comparisons between paired groups were carried out by the Wilcoxon matched-pairs signed-ranks test. A corrected p<0.05 was considered statistically significant.A total of 80 of 957 serum samples were detected by both the nephelometric assay and ELISA method. The findings of our established ELISA method agreed well with those of the nephelometric assay . The cos-1•d-1 was the initial dose of steroid, and the dosage of medications was reduced according to the condition of each patient; In this study, serum IgG4 concentrations were significantly higher in IgG4-RD than in other diseases  were found in patients with other autoimmune diseases(8/127),nephropathy(2/36), digestive diseases(4/60), hematological diseases(1/38), neurological disorders(2/24), respiratory disorders(3/24), carcinoma(11/535), and other conditions(1/47) .Unexpectedly, the highest positive rate of serum IgG4 levels in non-IgG4-RD was 8.33% in neurological disorders,which represented 2 patients with cerebral infarction. The second highest group in this study was 6.67% of patients with digestive diseases, including 3 patients with cirrhosis and 1 with colon polyps. The positive rate of serum IgG4 concentrations in other autoimmune diseases was 6.3%, including 2 patients with ankylosing spondylitis, 2 patients with rheumatoid arthritis, 3 patients with myositis, and 1 patient with suspected connective disease who had elevated serum IgG4 levels (>1.35 g/L). Instead, the positive rate of serum IgG4 in carcinoma was 2.06%, as elevated serum IgG4 levels were determined in 2 lung carcinoma cases (1.39 and 3.84 g/L), 2 rectal carcinoma cases (1.58 and 3.8 g/L), 1 hepatoma case (2.13 g/L), 1 gallbladder carcinoma case (1.63 g/L), 1 cholangiocarcinoma case (2.85 g/L), 1 penile cancer case (1.54 g/L), 2 Acute Myelocytic Leukemia cases , and 1 left elbow pleomorphic undifferentiated sarcoma case (1.435 g/L) . Other nElevated serum levels of IgG4 provide an opportunity to identify IgG4-RD. At present, high serum IgG4 concentrations are recognized as a vitally important diagnostic criterion for IgG4-RD. In addition, it was reported that the serum IgG4 concentrations were associated with the disease activity. To someTwo techniques to measure serum IgG4 levels have been documented so far: the nephelometric assay and the ELISA method. The former method has been widely used in the clinic. A high hook effect can occur in the nephelometric assay, resulting in false negative outcomes. Furthermore, in the nephelometric assay, test results of serum IgG4 levels can differ when the same reagents are obtained from distinct corporations . HoweverThose serum samples with IgG4 concentrations >1.35 g/L, which was defined as the cutoff value, showed great sensitivity and specificity , and a serum ratio of (IgG4/IgG) > 8 demonstrated an increased specificity of 87.5% for IgG4-RD . If a seThe results of our study illustrated that the positive rate of serum IgG4 levels was 3.39% in non-IgG4-RD patients. We found that 2.06% of carcinoma entities were associated with a positive serum IgG4 titer, including cases of hepatocellular carcinoma, gallbladder carcinoma, lung neoplasms, colorectal cancer,hematologic malignancies,etc . Determi+/IgG+ plasmacytes >40% and IgG4-positive plasmacytes >10 per HPF from pathological assessments are equally important in the diagnosis of IgG4-RD.By contrast, a high positive rate of serum IgG4 was observed in neurological disorders (8.33%) and digestive diseases (6.67%). These positive cases included cerebral infarction (2 cases), cirrhosis (2 cases), and colon polyps (1 case). Additionally, 6.30% of patients with autoimmune diseases exhibited high serum IgG4 levels (>1.35g/L), including 2 patients with ankylosing spondylitis, 2 patients with rheumatoid arthritis, 3 patients with myositis, and 1 patient with suspected connective disease. Based on the medical literature, elevated levels of IgG4 have been found to be associated with liver cirrhosis ,22 and aTaken together, our newly established ELISA method is convenient and relatively stable for detecting serum IgG4 concentrations, and can be widely used in the clinic. It makes sense only when serum IgG4 level is much higher than 1.35g/L for the diagnosis of IgG4-RD. Differential diagnoses should be made for suspected IgG4-RD cases with high serum IgG4 titers.Our newly established ELISA technique can be used in the clinic to measure serum IgG4 levels. Elevated serum IgG4 concentrations can be observed in conditions other than IgG4-RD.


Introduction. Adipose tissue is the largest endocrine organ, composed of subcutaneous (SAT) and visceral adipose tissue (VAT), the latter being highly associated with coronary artery disease (CAD). Expansion of epicardial adipose tissue (EAT) is linked to CAD. One way of assessing the CAD risk is with low-cost anthropometric measures, although they are inaccurate and cannot discriminate between VAT and SAT. The aim of this study is to evaluate (1) the relationship between EAT thickness, SAT thickness and anthropometric measures in a cohort of patients assessed at the cardiology unit and (2) determine predictive power of anthropometric measures and EAT and SAT thickness in establishment of CAD. Methods. Anthropometric measures were obtained from 53 CAD and 42 non-CAD patients. Vascular and structural statuses were obtained with coronarography and echocardiography, as well as measurements of the EAT and SAT thickness. Results. Anthropometric measures showed moderate positive correlation with EAT and SAT thickness. Anthropometric measures and SAT follow nonlinear S curve relationship with EAT. Strong nonlinear power curve relationship was observed between EAT and SAT thinner than 10 mm. Anthropometric measures and EAT and SAT were poor predictors of CAD. Conclusion. Anthropometric measures and SAT have nonlinear relationship with EAT. EAT thickness and anthropometric measures have similar CAD predictive value. The majority of adipose tissues in the human body are deposited as subcutaneous or visceral fat, differing in their structure and function [The most common chronic disorder nowadays is obesity, which is defined as excessive accumulation of adipose tissue (fat), traditionally defined with body mass index (BMI) exceeding 30 kg/mfunction . Subcutafunction . Obesityfunction , 6. Partfunction , 8. Abdofunction . Since Bfunction .Coronary heart disease is the leading cause of death worldwide. Coronary angiography is the criterion standard for detecting significant flow-limiting stenosis and direct imaging of atherosclerotic changes in coronary arteries. Because of the inherent limitations, disadvantages and complications of coronary angiography, attention has been directed toward using physiologic, noninvasive modalities to determine the severity of coronary stenosis. Epicardial adipose tissue thickness has been reported as a marker for the presence and severity of coronary artery disease , 4, 11, Due to limited research in the field, we performed the detailed analysis of the relationship between anthropometric measures , WHR, BMI, and waist-to-height ratio) and echocardiographically obtained EAT and SAT thickness in a cohort of patients admitted at the cardiology unit. We also tested power of these “classical” and ultrasound anthropometric measures for the prediction of CAD.2. Due to clinical symptoms all subjects underwent echocardiography and coronarography at the Cardiology Department of Clinical Hospital Center Osijek, Croatia. Exclusion criteria were diabetes and chronic renal failure.In this study 95 Caucasian subjects were included, 55 males and 40 females, all of whom signed an informed consent. Subject's age spanned from 31 to 80 years, with BMI of 19.9 to 38.7 kg/mUltrasound measurements of EAT thickness were performed with Siemens Acuson V70 and linear probe L10 5–11 MHz) and SAT thickness with probe P4-2 . EAT thickness was assessed using M mode in long parasternal axis with subject in left lateral decubitus position. The EAT was identified as echo-free space between the myocardial wall and the visceral layer of pericardium in end-diastole above right ventricle  MHz and . SubcutaAnthropometric measures were taken in all subjects in standing position, while being barefoot on a flat surface, after exhaling, at a level parallel to the floor , using a stretch-resistant measuring tape to the nearest 1 mm. All anthropometric measures were measured to one decimal. Waist circumference was measured at the approximate midpoint between the lower margin of the last palpable rib and the top of the iliac crest. Hip circumference was measured around the widest portion of the buttocks. Body weight was measured using electronic calibrated scales to the nearest 100 grams, while subjects wore minimal clothing. Each measurement was repeated twice.t-test (CI of 95%). Correlation was used to explore the nature of relationships among variables. Curve estimation models were used to assess the relationships among anthropometric variables, EAT and SAT thickness. ROC analysis was used to determine predictive capabilities of anthropometric variables EAT and SAT thickness for CAD. Accepted statistical significance was for p < 0.05.Data analysis was performed using SAS software . Data in tables were reported with mean value and a standard deviation. Normality of distribution was tested using the Shapiro-Wilks test. Group comparisons were done using Mann-Whitney test and Student's n = 53) if they had ≥50% narrowing of one or more coronary arteries or to control, non-CAD group (n = 42), in which different valvular abnormalities were established. Subjects in the groups were of similar age and BMI. Larger values of waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), EAT thickness, and SAT thickness were observed in CAD patients  (Relationship between anthropometric variables (except WHR) and EAT thickness was described the best as a nonlinear Figures . An S cutionship . Visual < 0.001) . When SA< 0.001) .p = 0.082), can detect CAD (p < 0.05), but with poor accuracy and similar sensitivity and specificity. Anthropometric variables and EAT and SAT had similar areas under curve. Using logistic regression for CAD prediction, overall model with anthropometric measures, SAT and EAT thickness as predictor variables were created and tested using ROC analysis. The overall model had moderate accuracy and the largest area under curve (AUC 0.751), while areas under curve for assessed measures ranged from 0.605 to 0.688 (Receiver operating characteristic (ROC) curves for CAD classification with anthropometric variables and EAT, SAT thickness showed that all predictor variables, except BMI , while SAT thicker than 10 mm is independent of EAT thickness, since we could not establish any linear or nonlinear relationship (All anthropometric variables (except WHR) and SAT thickness, independently of each other, showed a nonlinearsubjects . As clastionship . This unAdipocytes in different compartments of adipose tissue enlarge by storing excess lipids, but when certain threshold overall volume of adipose tissue is reached, they cannot accumulate lipids anymore. It was shown that every person enters early adulthood with specific number of adipocytes, which can only be hypertrophy when accumulation of lipids occurs, while hyperplasia of precursors is strictly regulated . Therefo in vitro, that leptin (mostly produced by SAT) was responsible for macrophage extravasation, important step in initiation of adipose tissue inflammation [μm in diameter, thus exciding oxygen diffusion distance [Adipose tissue expands and undergoes extensive remodeling during positive caloric balance . Adiposeammation . Along wammation . Hypoxiaammation . Hypoxiadistance . These pMoreover, accumulation of total adipose tissue leads to general low-grade inflammation, resulting in development of atherosclerosis . InflammIn conclusion, in cardiac patients, the EAT thickness follows a nonlinear relationship with anthropometric measures and SAT thickness. Ultrasound measures of EAT thickness have similar predictive accuracy for CAD to anthropometric measures of visceral obesity.


Shared Decision Making (SDM) is increasingly advocated as a model for medical decision making. However, there is still low use of SDM in clinical practice. High impact factor journals might represent an efficient way for its dissemination. We aimed to identify and characterize publication trends of SDM in 15 high impact medical journals.We selected the 15 general and internal medicine journals with the highest impact factor publishing original articles, letters and editorials. We retrieved publications from 1996 to 2011 through the full-text search function on each journal website and abstracted bibliometric data. We included publications of any type containing the phrase “shared decision making” or five other variants in their abstract or full text. These were referred to as SDM publications. A polynomial Poisson regression model with logarithmic link function was used to assess the evolution across the period of the number of SDM publications according to publication characteristics.We identified 1285 SDM publications out of 229,179 publications in 15 journals from 1996 to 2011. The absolute number of SDM publications by journal ranged from 2 to 273 over 16 years. SDM publications increased both in absolute and relative numbers per year, from 46  in 1996 to 165 (1.17%) in 2011. This growth was exponential (P < 0.01). We found fewer research publications  than non-research publications, which included non-systematic reviews, letters, and editorials. The increase of research publications across time was linear. Full-text search retrieved ten times more SDM publications than a similar PubMed search (1285 vs. 119 respectively).This review in full-text showed that SDM publications increased exponentially in major medical journals from 1996 to 2011. This growth might reflect an increased dissemination of the SDM concept to the medical community. Shared decision making (SDM) is increasingly advocated as a model of best practice for decision making in the medical encounter -3. SDM hResearch publications whose main topic is not necessarily SDM may not mention the phrase “shared decision making” in the title or the abstract, but only in the discussion. Editorials, reviews or debates, among other publication types, do not have abstracts but have a potential impact on the reader. Moreover, not every single phrase is indexed in PubMed. All these publications might then be missed out by a systematic search of titles, abstracts and keywords on PubMed ,13. In cWithin the last years, SDM increasingly appears in editorials and articles’ discussions in high impact medical journals. However, no reliable data can support this assertion. Such journals play a major role in the dissemination of new medical evidence ,16. The Cochrane Database of Systematic Reviews, in order to cover various types of publications, such as research publications and editorials, and to reduce heterogeneity between journals.We selected the 15 journals with the highest 5-year impact factor in 2010 based on the ISI Web of Knowledge Journal Citation Reports, ,18 in thWe retrieved publications through the full-text search function on each journal website, usually located on the “advanced search” web page or on the publisher website if not available. We typed chosen keywords as a phrase in double quotes in the search box. We used this search method, defined as website full-text search, because it allows finding publications with a search term not necessarily in the title or abstract, but in the article sections in full text. This is not possible through a PubMed search as full texts are not available on the PubMed search engine. We included publications of any type, with the exception of cover pages, tables of content and indexes .To identify publications relating to SDM, referred to as SDM publications, we first chose the phrases “shared decision making” and “informed decision making” because they are the most often encountered in medical literature . To imprWe included publications released between January 1996 and December 2011, because the concept of SDM began to appear significantly in medical literature since the mid-1990s ,19. Morestatus quo) by providing (at the minimum) information on the options and outcomes relevant to a person’s health status and implicit methods to clarify values” [We abstracted the following bibliometric data from the full text of included SDM publications on a prespecified electronic form : journal, publication year, publication type, publication topic, and exact phrase relating to SDM. Publications assessing decision aids were distinguished from those that did not. We categorized publications into 9 types adapted from the indexing methods of PubMed, Embase, and previous bibliometric studies -23. We g values” . Two aut values” .This novel search method relied on journal/publisher websites whose search strategies were not explicit, in contrast to PubMed searches. To compare our method results with a validation dataset, we contacted the editorial board of each journal to request authorisation to obtain all published materials since 1996. After receiving authorisation from the journals (n = 6/15), we collected published materials and launched an automated search script . We used the same six phrases relating to SDM for publication retrieval. This text retrieval method on a locally stored full-text corpus was defined as downloaded full-text search . We asseTo assess the performance of the website full-text search, we compared it with a PubMed search using a similar strategy, i.e. using the same six phrases relating to SDM in the 15 journals between 1996 and 2011. We typed the six phrases in double quotes in the search box, so that the PubMed search looked for the exact phrase in all fields, such as the titles and abstracts, but also indexed terms and other metadata recorded by PubMed database.We first conducted simple descriptive statistics of publications in each journal. We compared the overall number of publications with the number of SDM publications from 1996 to 2011. We assessed descriptive statistics of bibliometric data of SDM publications. We used a polynomial Poisson regression model with logarithmic link function ,29 to asThe results of the full-text search on the journal websites are shown in Figure Annals of Medicine to 273 in the BMJ over 16 years  in 1996 to 165 (1.17%) in 2011. In a Poisson model (see equations in figures footnotes), this increase in absolute numbers was significant  and exponential .The number of SDM publications was much larger in 2011 than during previous years  than non-research publications , end-of-life care , and cardiovascular system  were the most frequent clinical topics , most of them randomized controlled trials Table . These pThe concordance rate was high (89.4%) between the downloaded and website full-text searches Figure . Two pubThe website full-text search identified about ten times more publications than a systematic search through PubMed (1285 vs. 119). Out of 119 publications, 3 were missed out by the website full-text search; one because of unavailable data on the journal website for years 1996–97 and two were available on the journal website but the remote search engine failed to retrieve them for an unknown reason.Two authors independently assessed a random selection of 173 publications out of the 1285 to measure the reliability of the dichotomized data of our prespecified form. The agreement rate and Cohen kappa between the two authors were as follows: for publication type, 95.4% and 0.89, respectively; for publication topic, 93.6% and 0.87, respectively; for publications assessing decision aids, 93.6% and 0.24, respectively.We found a significant and exponential increase in the number of SDM publications in the 15 highest impact factor journals in general internal medicine between 1996 and 2011. Nevertheless, the number of SDM publications across the journals varied widely. When focusing on research publications, the growth was not exponential but remained mostly linear since 1996. We observed few publications assessing decision aids, however their growth pattern was similar to the general trend.Several studies have explored the frequency of concepts in medical literature ,21 or foMore recently, a bibliometric analysis assessed the quality as well as the volume of research in primary care between countries . Our revJournal of General Internal Medicine released fifty times more publications than the last journal in the top 15. This variation may be partially explained by differences in editorial choices, which were not studied here. Nevertheless, the trends were analysed according to various components. Breaking down the increase in SDM publications into bibliometric data brought some keys to better understand it.Another study measured the distribution of topics in two major medical journals by disease categories and domains over a calendar year . They foTo our knowledge combining techniques of review through full-text search and bibliometric analysis has not been reported before. Full-text search techniques have been used in biomedicine,  especialOur study has some limitations. First, our study was limited to the 15 major medical journals chosen according to their impact factor. Despite the widespread use of the impact factor metric,  it has iSecond, categorising publication types from 15 different journals was limited by our a priori criteria as each journal has its own indexing method. Our category list was developed internally, inspired by PubMed and Embase classifications, yet we reached a high degree of agreement between both reviewers . The discrepancy between agreement rate (93.6%) and Cohen kappa (0.24) on publications assessing decision aids could be explained by the imbalance of the 2×2 table and the low number of publications reporting on decision aid tools ,42.Third, we did not divide papers into those where the concept of SDM was the primary topic and those where the concept was briefly mentioned. Our aim was to perform a scoping review of the concept of SDM in the selected medical journals. Future, more detailed studies could aim at better understanding if the concept was used as the primary topic or if authors just mentioned it.PLOS Medicine and the Annals of Family Medicine). We cannot determine if the trends in SDM would have been different in open access journals. Future studies might aim at determining if the trends in SDM are different between open access and other journals.Fourth, two journals did not exist before 1996 and were therefore excluded from our analyses. These were two open access journals (Finally, if we showed an increase in the number of SDM publications, we did not assess to which extent the medical community reads them. Therefore, the impact of this increase remains unknown. A future study could alternatively focus on the number of citations per SDM publication compared to citations of other publications .The growth in SDM publications found in our study nevertheless supports the call of experts in the field for the medical community to implement SDM in practice ,3,44,45.SDM has been called to ensure evidence-based patient choice, especially for equipoise situation . Even thThis study shows that SDM publications increased exponentially in major medical journals from 1996–2011. This growth might reflect an increased dissemination of the SDM concept to the medical community. We explored a novel methodology by combining review through full-text search with bibliometric analysis. The methodology permitted a thorough retrieval of SDM publications and a precise analysis of the dissemination of SDM in medical literature.The authors declare that they have no competing interests.RA, THC, XB were involved in the design, implementation, and analysis of the study. FL and JC were involved in the design and analysis of the study. RF and XB abstracted data. IL did the statistical analysis. PI and JK were responsible for the downloaded full-text search. XB drafted the manuscript. All authors were involved in the interpretation of the findings. All authors critically read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6947/14/71/prepubSelection of 15 journals in general internal medicine.Click here for file


Ocular adnexal IgG4-related sclerosing disease (IgG4-SD) has been categorized as a novel disease entity. It is characterized by stromal sclerosis and an infiltration of mass-forming lymphoplasmic cells containing many IgG4-positive plasma cells. Although ocular adnexal tissue involvement has been increasingly reported, a focal nodular sub-brow mass is not typical in an IgG4-SD presentation. We report a rare case of probable ocular adnexal IgG4-SD that clinically mimicked eyelid pilomatrixoma.A 42-year-old woman presented with a nodular mass in her left sub-brow area. The initial clinical impression of her lesion was eyelid pilomatrixoma. However, the final pathologic diagnosis was IgG4–SD, but extranodal marginal zone B-cell lymphoma could not be excluded. The patient underwent testing to determine tumor malignancy and systemic IgG4-SD involvement. Laboratory testing showed normal IgG and IgG4 serum levels and imaging revealed no remarkable findings. Oral prednisolone was administered and slowly tapered to manage the possible remnant lesion and to prevent disease recurrence. Two years after initiating therapy, there was no evidence of relapse. The patient is under close surveillance for signs of recurrence, systemic involvement, and potential malignant transformation.We found an unusual case of probable ocular adnexal IgG4-SD, which presented as a unilateral restricted mass involving the sub-brow area. Although the mass was surgically removed, systemic steroid treatment and long-term surveillance were initiated due to the possibility of recurrence, the potential association with systemic disease, and the potential development of extranodal mucosa-associated lymphoid tissue (MALT) lymphoma. Ocular adnexal IgG4-related sclerosing disease (IgG4-SD) has been categorized as a novel disease entity that may account for a certain proportion of idiopathic ocular and periocular inflammatory lesions. It is characterized by stromal sclerosis and an infiltration of mass-forming lymphoplasmic cells containing many IgG4-positive plasma cells. It can involve various organs including pancreas, bile duct, retroperitoneal soft tissues, liver, thyroid, lung and salivary glands, either singly or systematically ,2. AlthoA 42-year-old woman with no significant past medical history presented with a painless nodular mass in her left upper lid, which had had slowly enlarged over 1 year. On clinical examination, a non-tender, nodular mass (5.5 mm × 4.5 mm) was palpable in the left sub-brow region and was freely mobile over subcutaneous tissue , 21.1mg/dL , respectively]. Serum Lactate dehydrogenase concentration was within normal range. Except for a 3 cm sized uterine myoma, imaging studies including chest CT, abdomen and pelvic CT, and positron emission tomography scanning demonstrated no remarkable findings.For the management of possible remnant lesion and prevention of recurrence of disease, oral prednisolone was administered at a 40 mg/day initial dose and was slowly tapered to a 2.5 mg/day maintenance dose. One year after initiating therapy, there was no evidence of relapse. The patient is under close surveillance for signs of recurrence, systemic involvement, and potential malignant transformation.Recognition of IgG4-SD is clinically important because this disease is, theoretically, a systemic disorder. Steroid therapy has been proposed to be effective, but relapse occurs frequently. Furthermore, recent studies suggest that IgG4+ plasma cells might be involved in the pathogenesis of mucosa-associated lymphoid tissue (MALT) lymphoma -8. MoreoTwo characteristics IgG4-SD include dense sclerosis with abundant IgG4+ plasma cell infiltration and serum IgG4 level elevation . In thisClinical examination showing characteristic diffuse/localized swelling or masses in single or multiple organsHematological examination shows elevated serum IgG4 concentrations( 135 mg/dl)Marked lymphocyte and plasmacyte infiltration and fibrosis.Infiltration of IgG4+ plasma cells: ratio of IgG4+/IgG+ cells > 40% and >10 IgG4 + plasma cells/HPF.Histopathologic examination shows:Definite: 1) + 2) + 3)Probable: 1) + 3)Possible: 1) + 2)We found an unusual case of probable ocular adnexal IgG4-SD, which presented as a unilateral restricted mass involving the sub-brow area. Although the mass was surgically removed, systemic steroid treatment and long-term surveillance was initiated due to the possibility of recurrence, the potential association with systemic disease, and the potential development of extranodal MALT lymphoma.Written informed consent was obtained from the patient for publication of this Case Report and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.


HER2, EGFR, MET, FGFR2 and KRAS, are target molecules that are clinically beneficial in gastric cancer (GC). We investigated the correlation between RTK-related genes and the curative effect of first-line S-1 plus cisplatin (SP) combination chemotherapy in metastatic and recurrent GC. We enrolled 150 patients with histopathologically confirmed metastatic and recurrent GC treated with SP. KRAS mutation was detected using direct sequencing. DNA copy number was measured by real-time PCR. Formalin-fixed paraffin-embedded specimens were examined immunohistochemically for HER2, EGFR, FGFR2 and MET. Among 144 patients, KRAS mutation was detected in five (3.5%) at codon 12 and one (0.7%) at codon 13. FGFR2, EGFR, HER2, MET and KRAS gene amplification was suggested in 4.4%, 5.9%, 9%, 3.7% and 10.3% of patients, respectively. KRAS mutation, but not KRAS amplification, was associated with significantly shorter overall and progression-free survival. MET membranous overexpression was associated with a significantly higher tumor response. MET amplification was associated with significantly shorter overall survival. We show for the first time that KRAS mutation and MET amplification are promising predictive markers in metastatic and recurrent GC patients treated with SP. KRAS status may be a useful prognostic marker in patients treated with SP.Receptor tyrosine kinase (RTK)-related genes, including  S1 plus cisplatin (SP) combination therapy was significantly superior to S1 alone as first-line treatment for metastatic and recurrent GC in the phase III SPIRITS trial . New molet al. . The other evaluation of HER2, FGFR2 and MET was performed according to the defined negativity (grade 0 and 1+) and positivity (grade 2+ and 3+). EGFR was evaluated according to the defined negativity  and positivity (grade 3+).Immunostaining was assessed and scored subjectively by two pathologists blinded to clinical characteristics and outcomes. For HER2, EGFR, MET and FGFR2, immunostaining of the tumor cell membrane was scored using a four-grade scale  and area percentage of positive cells (0–100%) in each grade according to scoring in GC. Immunostaining of the tumor cell cytoplasm was scored using a four-grade scale  and area percentage of positive cells in each grade. MET and FGFR2 reactivity was scored as 0 if there was no cytoplasmic reactivity within the tumor, or as 1+, 2+ or 3+ depending on the intensity above the background level. For HER2, EGFR, FGFR2 and MET, we calculated H score by multiplying the staining intensity  with the percentage of positive cells at each grade, and all values were added to obtain the final immunohistochemistry score, ranging from 0 to 300. HER2, EGFR and MET were scored using a four-grade scale  according to Hofmann's criteria . FGFR2 w2 test with 1 degree of freedom.The primary endpoint of this retrospective study was OS, and the secondary endpoint was PFS. OS was defined as the period from starting therapy to the date of death or censoring of the last contact if alive. PFS was defined as the interval from the first day of starting first-line SP therapy to the first day of documented disease progression or death. If progression or death was not observed, PFS was censored on the day of the last computed tomography scan. All factors were tested for deviation from Hardy–Weinberg equilibrium using the χ2 tests and in the multivariate analysis using a logistic regression model controlling for potential predictive variables. P values for all factors were adjusted for multiple testing using a modified test of Conneely and Boehnke that was applied for the correlated tests owing to linkage disequilibrium and the different modes of inheritance considered.The associations between all factors and OS and PFS were examined in univariate analysis using Kaplan–Meier estimation and Cox–Mantel tests, and in multivariate analysis using a Cox proportional hazards regression model. The following baseline characteristics were adjusted in the multivariate analysis: sex, age, Eastern Cooperative Oncology Group performance status, Lauren classification, tumor location, primary tumor resection, lung metastases, liver metastases, peritoneal metastases, lymph node metastases, and ≥2 metastases. The relationships between all factors and response were assessed in the univariate analysis using χhttp://www.r-project.org) was used to conduct all the analyses by Sugimoto Data Analysis Service . All tests were two-sided at a significance level of 0.05.R version 3.2.0 software (


P = 0.09). Patients aged ≤65 years had greater mortality benefit  than patients that were older than 65 . No effect was observed on incidence of Clostridium difficile , and multidrug-resistant organism  infections. No increase in infection-related readmission  was found in survivors. Receipt of CDSS-recommended antibiotics reduced mortality risk in patients aged 65 years or younger and did not increase the risk in older patients. Physicians should be informed of the benefits to increase their acceptance of CDSS recommendations.Antibiotic computerised decision support systems (CDSSs) are shown to improve antibiotic prescribing, but evidence of beneficial patient outcomes is limited. We conducted a prospective cohort study in a 1500-bed tertiary-care hospital in Singapore, to evaluate the effectiveness of the hospital’s antibiotic CDSS on patients’ clinical outcomes, and the modification of these effects by patient factors. To account for clustering, we used multilevel logistic regression models. One-quarter of 1886 eligible inpatients received CDSS-recommended antibiotics. Receipt of antibiotics according to CDSS’s recommendations seemed to halve mortality risk of patients (OR 0.54, 95% CI 0.26–1.10,  Antibiotics are among the major developments in modern medicine, saving countless lives over the decades2Overuse and misuse of antibiotics have driven the emergence of antimicrobial resistance62491012131415164184Antimicrobial stewardship can improve antibiotic prescribing and clinical outcomes in hospital inpatients13Clostridium difficile infection (CDI), and multidrug resistant organism (MDRO) infection, and the modification of these effects by patient factors.We conducted a prospective cohort study to evaluate the effectiveness of a tertiary hospital’s in-house antibiotic CDSS, “Antimicrobial Resistance Utilization and Surveillance Control” (ARUSC), on mortality, readmission, incidence of The study was conducted in Tan Tock Seng Hospital, a 1500-bed tertiary-care academic centre that serves a diverse ethnic, adult medical and surgical population in Singapore. In 2009, the hospital launched its antibiotic CDSS, “ARUSC”, which integrates antimicrobial stewardship with the hospital’s computerised physician order entry system (CPOE) and provides patient-specific evidence-based antibiotic recommendations at the point of prescribing16From September 12, 2011, whenever a physician makes an electronic prescription of piperacillin-tazobactam or a carbapenem for an inpatient, the prescription automatically triggers the launch of ARUSC. Piperacillin-tazobactam and carbapenems are antibiotics of last resort for many bacterial infections, particularly those caused by multidrug-resistant pathogens. Hence, it is crucial to ensure the judicious use of these antibiotics.All patients admitted to the hospital, from October 1, 2011 through September 30, 2012, who were prescribed piperacillin-tazobactam or a carbapenem for empirical therapy and automatically triggered to receive antibiotic recommendations by ARUSC were included in the study. We included only the first prescription for empirical therapy per patient during the study period. Empirical therapy is the initiation of antibiotic treatment prior to the identification of the infection-causing microorganism. Using a rules-based algorithm, ARUSC provides guidance on antibiotic selection and dosing, based on guidelines developed by the hospital’s antimicrobial stewardship committee, which took into account the local epidemiology of infectious diseases, microbiologic resistance patterns, and incorporated evidence-based international guidelines. Inputs from all clinical departments were considered in the development of the guidelines, which were endorsed by the hospital’s medical board. ARUSC recommends the narrowest-spectrum antibiotic appropriate for common organisms responsible for the diagnosed infection, based on the local epidemiology and antibiotic susceptibility patterns, taking into account the patient’s antibiotic allergies and renal function . The prePrescriptions for prophylactic or definitive therapy were excluded from the study. We chose to focus our study on empirical therapy, as empirical antibiotic prescriptions were the least concordant with antibiotic guidelinesWe assembled a prospective observational cohort, starting from the automatically-triggered launch of ARUSC at the point of antibiotic prescribing up to 30 days post-hospital discharge or 180 days post-antibiotic prescription, whichever was later.C. difficile toxin and C. difficile-specific enzyme glutamate dehydrogenase antigen using the Techlab C. difficile Quik Chek Complete test, without a positive test during the preceding 8 weeks (repeat positive tests during this period suggest recurrence rather than incidence)C. difficile polymerase chain reaction test for the presence of C. difficile genetic material was carried out. We defined MDRO as a bacterium that is resistant to three or more of five antibiotic classesWe selected 30-day all-cause mortality as the primary outcome, since the key benefit of appropriate empirical antibiotic therapy is 30-day survival gainPatients’ receipt of antibiotics recommended by ARUSC was determined by electronically matching antibiotics prescribed in the institutional CPOE system with those recommended by ARUSC. A patient was classified as having received an ARUSC intervention if the prescribed antibiotics and those recommended by ARUSC matched exactly on the dose, route, and frequency of administration.Relevant patient characteristics included socio-demographic data , co-morbidities, illness severity, admission to an intensive care unit (ICU) at the time of prescribing, prior antibiotic exposure within 180 days and proton pump inhibitor exposure within 90 days preceding current prescription, prior hospitalisation within 90 days preceding current admission, diagnosed infection for current antibiotic therapy, and the time and day of week when the prescription was made.et al.We dichotomised age to <=65 and >65 years, representing younger and older age groups. Ward class was based on admission to a private or subsidised room, and used as a surrogate measure of the patient’s socioeconomic status. We defined co-morbidities as follows. Diabetes mellitus: a diagnosis of diabetes with or without complications. Cardiovascular disease: coronary artery disease or congestive heart failure. Liver disease: liver disease of any severity. Renal disease: moderate to severe renal disease. Neoplasm: solid malignant tumour, leukaemia, lymphoma, or any metastasis. Central nervous system (CNS) disease: cerebrovascular disease, dementia. Chronic pulmonary disease: chronic obstructive pulmonary disease. Charlson’s co-morbidity index (CCI)The prescribing physician was the physician who initiated the empirical antibiotic prescription that led to the automatically-triggered launch of ARUSC. The attending physician was the physician who was primarily responsible for the patient’s clinical care and outcome for the particular hospitalisation episode. Physicians’ characteristics that were collected included the prescribing physician’s seniority, and the attending physician’s ethnicity and clinical specialty. The seniority of the prescribing physician was determined by the physician’s designation. Interns and residents were classified as juniors, and fellows and attending physicians as seniors. Data on the physician’s designation and ethnicity were obtained from the institution’s human resource database and matched to the physician’s identity and clinical specialty data in ARUSC.a prior as factors associated with each clinical outcome particularly those based on prior knowledge to be associated with adherence to antibiotic guidelines in general (not specific for antibiotic CDSSs due to limited information on antibiotic CDSSs). Statistical interactions between age, comorbidities, infectious diagnoses, illness severity, and receipt of antibiotics according to ARUSC’s recommendations, were respectively explored and product terms included in the models where appropriate. The percentages of the total outcome variances that could be explained by differences between prescribing physicians, attending physicians, and clinical specialties respectively were computed31First, we used appropriate descriptive statistics to summarise patients’ characteristics, their respective prescribing and attending physicians and clinical specialties, their receipt of antibiotics according to ARUSC’s recommendations, and subsequent clinical outcomes by diagnosed infection. Next, we explored relationships between the receipt of ARUSC-recommended antibiotics, various patients’ and physicians’ characteristics, and each clinical outcome using multilevel logistic regression models with random intercepts. We fitted two types of such models: model 1 involved nesting of patients within their prescribing physicians, and model 2 nested patients within their attending physicians who in turn were nested within their clinical specialties, to account for clustering within prescribing physicians and clustering within attending physicians and clinical specialties respectively. We then constructed multivariable adjusted multilevel logistic regression models, accounting for potential confounding. We included variables decided Ethical approval for the study was obtained from the National Healthcare Group Domain Specific Research Board and UCLA Institutional Review Boards. The study’s methods were carried out in accordance with the approved guidelines. A waiver of informed consent was granted.During the one-year study period, a total of 1886 unique inpatients, among 380,800 patient-days, at Tan Tock Seng Hospital were automatically triggered to receive antibiotic recommendations by ARUSC for prescriptions of piperacillin-tazobactam or a carbapenem for empirical therapy.Pneumonia  (64.3%) was the most commonly diagnosed infection, among which patients were the oldest  . PatientOn univariate analysis, patient factors were similarly associated with 30-day all-cause mortality in both models . Age > 6After controlling for potential confounding in the multivariable multilevel models, receipt of antibiotics according to ARUSC’s recommendations was marginally associated with mortality reduction . Age > 65 , CCI > 5 , sepsis , and ICU admission  were all positively associated with mortality.In the propensity score (PS) adjusted multivariable models, the effect of receipt of antibiotics according to ARUSC’s recommendations  remained, and the effects of CCI > 5  and ICU admission  were enhanced . The proWe selected the PS adjusted two-level model  as the final multivariable model, as the model provided the optimal fit overall. Interactions between the receipt of antibiotics according to ARUSC’s recommendations and age, comorbidities, illness severity, and infectious diagnoses were assessed. Age > 65 was found to interact positively with the receipt of antibiotics according to ARUSC’s recommendations , and the product term was included in the final model.P = 0.09) (P = 0.05). It did not have an effect on mortality in older patients >65 years old  (P = 0.004)  . In pati = 0.16) . Our stu= 0.004) . Effect P = 0.97) and MDRO infection . After discharge from hospital, patients who received ARUSC-recommended antibiotics did not have an increased rate of 30-day infection-related readmission .The multivariable two-level regression including the propensity score showed that ARUSC recommendations had no effect on the subsequent development of CDI . After adjusting for potential selection bias, the beneficial effect of ARUSC recommendations on 30-day all-cause mortality remained . There was no change in the non-effect on the subsequent development of CDI and MDRO infection, and 30-day infection-related readmission in survivors.With the correction of potential misclassification of CCI, the effect of ARUSC recommendations on 30-day all-cause mortality was unchanged , and did not increase the risk in older patients >65 years old . A recent meta-analysis on the effect of antimicrobial stewardship interventions intended to increase appropriate antimicrobial therapy for all infections reported no increase in mortality 1334P = 0.029)P = 0.02)23P = 0.04)1We found that the receipt of antibiotics according to the CDSS’s recommendations reduced the risk for 30-day all-cause mortality in patients aged 65 years and below , but did not observe a difference in infection-related readmissions between intervention and control groupsAmong survivors, patients who received CDSS-recommended antibiotics did not have an increased rate of 30-day infection-related readmission. Other studies have observed an increase in hospital readmissions associated with antimicrobial stewardship interventions intended to decrease excessive prescribing .