There is an increased risk of developing ovarian cancer (OC) in patients with endometriosis. Hence, development of new biomarkers may provide a positive clinical outcome for early detection. MicroRNAs (miRNAs) are small non-coding RNAs that play an important role in biological and pathological process and are currently used as diagnostic and prognostic markers in various cancers. In the current study, we assessed the differential expression of miRNAs from 19 paired ovarian cancer and its associated endometriosis tissue samples. In addition we also analyzed the downstream targets of those miRNAs.Nineteen paired cases of ovarian cancer and endometriosis foci were identified by a gynecologic pathologist and macro-dissected. The total RNAs were extracted and subjected to comprehensive miRNA profiling from the pooled samples of these two different entities using microarray analysis. Later, the abnormal expressions of few selected miRNAs were validated in individual cases by quantitative real-time PCR (qRT-PCR). Ingenuity pathway analysis revealed target mRNAs which were validated by qRT-PCR.miR-1, miR-133a, and miR-451 were reduced significantly (p<0.0001) in the OC patients compared to its associated endometriosis. In contrast, the expression of miR-141, miR-200a, miR-200c, and miR-3613 were elevated significantly (p<0.05) in most of the OC patients. Furthermore, among the downstream mRNAs of these miRNAs, the level of PTEN expression was significantly (p<0.05) reduced in OC compared to endometriosis while no significant difference was observed in NF-κB expression.The miRNA profiling identified deregulation of greater than 1156 miRNAs in OC, of which the top seven were further validated by qRT-PCR. The expression of The expression of miRNAs and mRNAs in OC were significantly different compared to its concurrent endometriosis. These differential expressed miRNAs may serve as potential diagnostic and prognostic biomarkers for OC associated with endometriosis. Ovarian cancer (OC) is the leading cause of cancer associated death among gynecologic malignancies . RecentlmiRNAs are a class of small, non-coding RNAs, which are involved in multiple normal biological pathways including cell differentiation, apoptosis, proliferation and metabolism by splicing and regulating mRNAs . ExperimEndometriosis is a common benign gynecological process defined pathologically as presence of endometrial glands and stroma outside of the uterus. It may cause pelvic pain, intestinal disorders and infertility . Many reIn our study, a comprehensive miRNA profiling from the OC and its concurrent endometriosis were compared to identify the key miRNAs that distinguish these two entities. Some of these miRNAs were further validated individually in each patient by direct comparison between paired endometriosis and OC samples using qRT-PCR. Furthermore, mRNA targets of these differentially expressed miRNAs were identified and validated individually using qRT-PCR. Identification of downstream targets of these miRNA may ultimately provide therapeutic targets in the future.We identified 49 cases of OC with concurrent endometriosis from the database of the pathology department of Wayne State University diagnosed between 1984–2012. After obtaining approval from the institutional review board, a retrospective chart review of the patient data was performed. Slides were reviewed by a gynecologic pathologist. Nineteen cases were confirmed to have OC with associated foci of endometriosis. Of these cases, five were endometrioid, eight serous and one clear cell carcinoma and five mixed carcinoma.Total RNA was extracted using RNeasy Kit  from formalin-fixed paraffin embedded (FFPE) tissue sections according to the manufacturer’s protocol with some modifications. The endometriosis foci and OC foci from each case were selected under microscope and macro-dissected precisely. Based on the size of the foci, 4–10 freshly cut tissue sections of 10 μm thick were placed in micro tubes along with 1 ml xylene. After vigorous shaking, samples were centrifuged for 2 min at room temperature. About 1 ml of ethanol was added and centrifuged for 2 min. The resultant pellet was resuspended in 240 μl of buffer PKD along with 10 μl of proteinase K and incubated at 55°C for 15 min, and then at 80°C for 15 min. The lower uncolored phase was transferred into a micro tube and centrifuged for 15 min at 20,000 g. The supernatant was next transferred to a new tube along with DNase I stock solution and DNase booster buffer and incubated at room temperature for 15 minutes. Approximately 500 μl of buffer RBC was then added and mixed with 1200 μl of ethanol and was subsequently applied to the RNeasy MinElute spin column and centrifuged at 8,000 g for 15 sec. The bound RNA was washed with RPE buffer solution twice to remove impurities and eluted with RNase free water. RNA was quantified and its purity evaluated by the absorption ratio at 260/280 nm using NanoDrop 2000 . The ratio of 260/280 varied from 1.8–2.1.Purified total RNAs were pooled separately from aliquots of 19 benign endometriosis or OC samples and submitted these two pooled RNAs (endometriosis and OC) for analysis using a service provider  for comprehensive miRNA microarray profiling. The miRNA profiling was performed by miRBase version 19 (LC Sciences). The data were normalized using selected housekeeping genes. Network analysis was accomplished with the web-based bioinformatics tool, Ingenuity pathway analysis software  to identify the target mRNAs from these differentially expressed miRNAs.Ct method and was normalized by RNU48 expression.Expression of the top seven differentially expressed miRNAs by microarray profiling was validated using quantitative real-time PCR (qRT-PCR). In brief, total RNA (10 ng) was reverse transcribed using specific miRNA primers and the TaqMan miRNA Reverse Transcription Kit . The resulting cDNA was used as input in a qRT-PCR using the miRNA specific probes mix and the TaqMan Universal PCR Master Mixture according to manufacturer’s protocol (Life Technologies). All reactions were performed in triplicate. The relative expression of miRNAs was analyzed using the Ct method and was normalized by GAPDH expression.The mRNA level of NF-κB and PTEN was determined by qRT-PCR using High Capacity RNA-to-cDNA kit . In brief, total RNA (500 ng) was reverse transcribed using High Capacity RNA-to-cDNA kit. The resulting cDNA was used as input in a qRT-PCR using NF-κB and PTEN primers together with the SYBR Green Master mix according to manufacturer’s protocol (Life Technologies). All reactions were performed in triplicate. The relative expression of mRNAs was analyzed using the t-test was used to determine the significance of differential miRNA expression between endometriosis and ovarian cancer obtained by qRT-PCR. The significance of PTEN and NF-κB mRNA level in individual cases was analyzed by student t-test. A level of P value < 0.05 was regarded as statistically significant and P value < 0.01 was regarded as statistically very significant.A paired The study cohort included nineteen cases of OC with concomitant endometriosis. All cases were morphologically confirmed by a gynecologic pathologist. The OC cases included one clear cell carcinomas, five endometrioid carcinomas, eight serous carcinomas and five mixed carcinomas . The chaAliquots of RNA extract from FFPE tissue blocks of ovarian cancer and benign endometriosis (approximately 200 ng each) were pooled separately. Microarray technology has permitted a comprehensive analysis of all miRNAs that are differentially expressed in OC and endometriosis. The Raw data of the comprehensive miRNA expression profiling has been deposited in NCBI’s Gene Expression Omnibus (GEO) which is a public functional genomics data repository and are accessible through GEO Series accession number GSE71477.miR-1, miR-133a, miR-451, miR-141, miR-3613, miR-200a, and miR-200c which were further validated individually using qRT-PCR as presented below.Expression profiling revealed 1156 miRNAs differentially expressed in subjects with ovarian cancer but not endometriosis. The 150 interesting miRNAs, that are differentially expressed in the ovarian cancer compared to endometriosis significantly (p < 0.05) with signal intensity larger than 500.00, are presented in miR-1, miR-133a, and miR451 showed significant reduction in ovarian tumors compared to their paired benign endometriosis (p < 0.001), as shown in miR-200a, miR-200c, miR-141, miR-3613, showed significant up-regulation in ovarian tumors compared to their benign endometriosis (p < 0.05)  .In order to comprehensively describe the pathways involved and their target genes, ingenuity modeling of the expression profiling of miRNAs was executed. Interestingly, among the different hubs that were activated in IPA derived networks, NF-κB and its related network mediator PTEN were found to be activated in OC samples as depicted in In order to further verify the target genes identified by IPA among ovarian cancer and endometriosis, we investigated the PTEN and NF-κB expression in paired samples of OC and endometriosis. The experiments were carried out in triplicate and in parallel to prevent batch effects. The mRNA values of PTEN and NF-κB were normalized using GAPDH mRNA. The relative changes in mRNA expression of PTEN and NF-κB of OC were first demonstrated by setting endometriosis level at 1.0. We observed significantly reduced PTEN expression in sixteen individual OC cases (16/19) when compared to endometriosis (p < 0.05) as presented in miR-1, miR-133a and miR-451 may serve as potential biomarkers in patients with endometriosis for screening for OC.Endometriosis is a common condition among reproductive-aged women affecting approximately 5% to 10% of women during their lifetime . There imiR-200a, miR-200b, miR-200c and miR-141 in ovarian cancer [miR-200a, miR-200c and miR-141 were observed between the OC and its concurrent endometriosis. These miRNAs belong to the same miR-200 family. The function of miR-200 family members and their interactions with other molecular components are the key to dissect the possible mechanisms that suggested the invasive features of OC. The most important targets of the miR-200 family are two E-box binding transcription factors, ZEB1 and ZEB2, which result in the inhibition of transcription of some epithelial polarity associated proteins, such as E-cadherin [miR-200 family members may transform tumor cells from indolent status to more aggressive and invasive phenotype. Elgaaen et al. reported over-expression of miR-200 family and under expression of ZEB1, ZEB2 and vimentin in high-grade serous ovarian carcinoma (HGSC) and clear cell ovarian carcinoma (COC) which were further confirmed by Ingenuity pathway analysis (IPA) documenting ZEB1 and ZEB2 as the most under expressed mRNAs in HGSC compared to ovarian surface epithelium [miR-200a, miR-200c and miR-141) may serve as biomarkers for OC during the emergence of invasive OC from normal reactive ovarian epithelial tissues or a benign entity, such as endometriosis. However, the role of EMT and MET related events associated with ZEB1, ZEB2, E-cadherin, vimentin and miR-200 family is highly complex, which certainly requires further investigation in the context of endometriosis and ovarian cancer.A recent study by Cao Q, et al. observed a significant increase in n cancer , which hn cancer . These cn cancer . In the cadherin . The dyscadherin . The E-ccadherin . Howevercadherin . BecauseMiR-1 is down regulated in many malignant tumors, such as non-small cell lung cancer, glioblastoma etc [C. elegans to human. It has also been shown to be involved in the angiogenesis during the muscular development of zebrafish [miR-1 in glioblastoma cells inhibited in vivo growth, neo-vascularization, and invasiveness [miR-1 expression was significantly down regulated in the OC compared to the benign endometriosis. It has been reduced by more than 1000 times in some of the OC samples. However, the exact mechanisms and its downstream targets by which it suppresses the tumorigenesis need to be further investigated.toma etc ,22. It iebrafish . Godlewssiveness . We haveMiR-451 was reported to be frequently down regulated in several types of tumors, [miR-451, such as calcium binding protein 39 (CAB39) [miR-451 was significantly dysregulated in the ovarian carcinoma. However, little is known about the miR-451 function and its mechanisms regarding the invasive behavior of OC and needs to be further studied. tumors,  such as  tumors, , lung ca tumors, , glioma  tumors, ,29 and b (CAB39)  which armiR-133a has been demonstrated in different types of carcinoma. Ectopic expression of miR-133a inhibited colorectal carcinoma (CRC) cell proliferation and migration. Over-expression of miR-133 suppressed the CRC proliferation and metastasis in vivo [LIM and SH3 protein 1 (LASP1) mRNA, that are CRC associated proteins [miR-133a in CRC [miR-133a suppressed the OC proliferation by targeting the insulin like growth factor receptor [miR-133a suppressed the OC cell proliferation and colony formation significantly by inducing the G1- phase cell cycle arrest [miR-133a suppressed in vivo tumor growth in nude mice [miR-133a in OC was observed in our study when compared to the benign endometriosis indicating the important role of miR-133a and it’s targeting mRNA in the formation of the ovarian carcinoma. This observation suggests that miR-133a may be used as biomarker and therapeutic target for diagnosis and therapy of OC.The down regulation of  in vivo ,31 by taa in CRC . Guo et Annunziata et al. found that NF-κB pathway is over activated in aggressive ovarian cancers and that some target matrix involved in the NF-κB pathway is associated with poor prognosis . TherefoDinulescu et al. demonstrated the direct link between endometriosis and endometrioid carcinoma through transgenic mouse model. Moreover, the tissue specific expression of mutant K-ras caused endometriosis while expression of active K-ras in combination with PTEN inactivation caused metastatic endometrioid carcinoma that resembled human OC . In the Significant differences between OC and its associated endometriosis were observed at the level of miRNAs transcription. Both tumor suppressor miRNAs  and oncogenic miRNAs  are possible molecules that distinguish ovarian cancer from its associated endometriosis. These miRNAs may be further studied to identify their role as possible mediated molecules in the development of ovarian cancer in patients with endometriosis. Identification and validation of downstream mRNA targets of these miRNAs, not only assists in the understanding of potential mechanisms involved in OC carcinogenesis, but also may lay the groundwork for new therapeutic targets in the future.


The aim of this study was to investigate the combined usefulness of platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) in predicting the long-term adverse events in patients who have undergone percutaneous coronary intervention (PCI) with a drug-eluting stent (DES).798 patients with stable angina, unstable angina and non-ST elevated myocardial infarction (NSTEMI) who underwent elective successful PCI with DES were consecutively enrolled. The value of PLR and NLR in predicting adverse coronary artery disease (CAD) events and the correlations between these markers and adverse events  were analyzed.The follow-up period was 62.8 ± 28.8 months. When patients were classified into four groups according to the optimal cut-off values for the PLR and NLR on receiver operating characteristic analysis, patients with a high PLR (>128) and high NLR (>2.6) had the highest occurrence of adverse events among the groups. On Cox multivariate analysis, the NLR >2.6  and the PLR >128  were independent predictors of long-term adverse events after adjusting for cardiovascular risk factors. Moreover, both a PLR >128 and a NLR >2.6 were the strongest predictors of adverse events .High pre-intervention PLR and NLR, especially when combined, are independent predictors of long-term adverse clinical outcomes such as all-cause mortality, cardiac death, and myocardial infarction in patients with unstable angina and NSTEMI who have undergone successful PCI with DES. Previous studies have shown that inflammatory response plays an important role in the progression and destabilization of atherosclerosis and cardiovascular diseases ,2. AmongAll consecutive eligible patients hospitalized at our institution between March 2003 and August 2007 due to stable angina pectoris or ACS  who underwent successful PCI with DES were retrospectively enrolled in this study. NSTEMI was defined as an increased value for cardiac troponin-T or CK-MB defined as a measurement exceeding the 99th percentile of a normal reference population on first assessment and at 6–9 hours later together with symptoms of ischemia, without typical ST elevation in electrocardiography .2. Out of the 994 eligible patients, 187 patients undergoing primary PCI for ST-segment elevation MI (STEMI) and 6 patients with unavailable laboratory data were excluded. Three patients were lost to follow-up after discharge from the hospital. Therefore, the remaining cohort consisted of 798 patients. This study protocol was approved by the Ulsan University Hospital Institutional Review Board (IRB) ethics committee and written informed consent was obtained from all participants.Patients with systemic diseases and on treatments potentially affecting the white blood cell count, including hematological disorders, malignancies, chemotherapy treatment, evidence of concomitant inflammatory disease, acute infection, chronic inflammatory conditions, history of corticosteroid therapy in the preceding 3 months, history of previous PCI or coronary artery bypass graft, secondary hypertension, heart failure, history of chronic renal or hepatic disease, and cerebrovascular disease were excluded from the study. We defined chronic renal disease as eGFR< 30 ml/min/1.73mComplete blood counts, which included the total white blood cells, neutrophils, lymphocytes, and platelets, were obtained from venous sampling at the time of admission. Cardiac enzymes (CK-MB and high sensitivity troponin T), glucose, creatinine, lipid profiles, and high sensitivity C-reactive protein (hs-CRP) were also measured in all patients. The PLR was calculated as the ratio of the platelet count to the lymphocyte count and the NLR was calculated as the ratio of the neutrophil count to the lymphocyte count. All patients were evaluated for the presence of cardiovascular risk factors.All patients received a 200 mg loading dose of aspirin, a 300 mg or 600 mg loading dose of clopidogrel at least 12 hours before the DES implantation, and an intravenous dose of unfractionated heparin (8000 IU or 100 IU/kg) after arterial puncture. Stents were implanted according to standard techniques. A successful PCI was defined as the attainment of an angiographic residual stenosis diameter of less than 30% and an antegrade flow of TIMI 3. Post PCI patients without contraindications remained on aspirin indefinitely and clopidogrel for at least 12 months.The primary endpoints were all-cause mortality, cardiac death, and nonfatal MI. Secondary outcomes were stroke, target vessel revascularization (TVR) and target lesion revascularization (TLR) based on the Academic Research Consortium (ARC) definition . CardiacThe Kolmogorov-Smirnov test was used for the evaluation of variable distribution. Continuous data with normal distributions were expressed as mean ± standard deviation, while categorical data is presented as the number of patients (%). The Chi-square test was used for comparison of categorical variables. We compared demographic characteristics and variables among the four groups using ANOVA tests for continuous variables and the Tukey method for post-hoc analysis. Receiver operating characteristic (ROC) curves were used to differentiate the ability of the PLR and NLR to predict adverse events . Cutoff values, sensitivity, and specificity were derived for each parameter. Survival curves were constructed based on cumulative incidences with Kaplan–Meier estimates and compared using the log rank test. The efficacy of the PLR and NLR in predicting adverse events was analyzed by univariate and multivariate Cox proportional hazards regression analyses adjusted for the variables with a significance level of p < 0.10 in univariate analysis. The statistical significance threshold was set at p < 0.05. Statistical analyses were performed using SPSS version 18.0 .A total of 798 patients  were included in the study and the median follow-up period was 62.8 ± 28.8 months. In total 51 adverse events occurred during the follow-up period, 5 adverse events occurred in 90 patients with stable angina and 46 adverse events occurred in 708 ACS patients (562 patients with unstable angina and 146 patients with NSTEMI). Among the 798 patients, 706 patients completed 1 year follow-up (92 patients were under 1 year and there were 16 deaths). Thirty-six patients had between 1–2 years follow-up, and a total of 670 patients completed both the 1 year and 2 years follow-up. Patients lost to follow-up (n = 112) were excluded from the analysis.On ROC analysis, the PLR and NLR were found to have the largest area under the curve  with an optimal PLR cut-off value of 128  and an optimal NLR cut-off value of 2.6  for predicting adverse events.Patients were classified into four groups based on the optimal cut-off values of the PLR and NLR: a low PLR and a low NLR , a high PLR and a low NLR , a low PLR and a high NLR , and a high PLR and a high NLR . Medications prior to PCI, both during the in-hospital period and at discharge, including antiplatelets (aspirin and/or clopidogrel), beta-blockers, renin-angiotensin-aldosterone system blockers, and statins, were similar among the groups. The angiographic characteristics based on groups are shown in All-cause mortality, cardiac death, and nonfatal MI, as well as the composite primary endpoints, were significantly higher in patients with a high PLR and high NLR compared to the patients with a low PLR and low NLR , Fig 1. Kaplan–Meier analysis revealed poor long-term survival and clinical outcomes in patients with a high PLR (PLR >128) . AdditioIn the present study, we showed that a high NLR and a high PLR on admission are independent predictors of long-term adverse events after successful PCI with DES in patients with ACS (unstable angina and NSTEMI). Additionally, our results showed that the combination of a high PLR and a high NLR is even more strongly predictive of future adverse events. To the best of our knowledge, this is the first study demonstrating the combined usefulness of the PLR and NLR for predicting the long-term adverse outcomes in patients who have undergone PCI with DES.There has been rapidly growing interest in the association between the NLR and the risk of cardiovascular events in patients undergoing angiography or cardiac revascularization –9. RecenRecently, the PLR, another marker of inflammation, has been evaluated as a prognostic marker in many cardiovascular diseases such as hypertension, CAD, and occlusive peripheral arterial disease –13. AlthInterestingly, from our results, hs-CRP levels were found to be significantly associated with both the NLR and PLR, and were the highest in patients with a high PLR and a high NLR. Moreover, hs-CRP level was also a significant independent predictor for the long-term adverse events in our study. Traditionally, hs-CRP has been well established as an inflammatory marker. However, in our experience, measuring the NLR and PLR is more cost-effective and frequently used than measuring hs-CRP. Considering the thrombosis and inflammation in patients with ACS might be different from those of stable angina , we perfThis study had several limitations. Firstly, the NLR and PLR were based on a single measurement. It would be interesting to see if the NLR and PLR changed over time or if on subsequent tests they remain a predictor of CAD severity. Secondly, despite not crucial to the aim of this study, use of first generation stents only may have been a limitation . MoreoveIn conclusion, a high pre-intervention PLR and NLR, especially in combination, are independent predictors of long-term adverse clinical outcomes such as all-cause mortality, cardiac deaths, and myocardial infarction in patients with unstable angina and NSTEMI who underwent successful PCI with DES.S1 Table(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.


Sporadic Creutzfeldt-Jakob disease (sCJD) might be transmitted by surgery. The purpose of this study was to investigate potential susceptibility to sCJD from surgery at juvenile age and in early adulthood.From Danish and Swedish national registries we identified 167 definite and probable sCJD cases with onset from 1987 through 2003, and 835 age-, sex- and residence-matched controls along with their surgical histories. Main, anatomically or etiologically classified surgical procedures followed by a ≥20-year lag were analyzed using logistic regression, and stratified by age at first-registered surgical discharge.The risk of having a diagnosis of CJD depended strongly on age at first surgery with odds ratio (OR) of 12.80 (95% CI 2.56–64.0) in patients <30 years, 3.04 (95% 1.26–7.33) in 30–39 years, and 1.75 (95% CI 0.89–3.45) in ≥40 years, for anatomically classified surgical procedures. Similar figures were obtained for etiologically classified surgical procedures.Risk of surgical-acquired sCJD depends on age at exposure; this pattern is similar to age-specific profiles reported for CJD accidentally transmitted by human pituitary-derived growth hormone and susceptibility curves for variant CJD estimated after adjustment for dietary exposure to bovine spongiform encephalopathy. There might be an age-at-exposure-related susceptibility to acquire all CJD forms, including sCJD from routine surgery. PRNP); acquired, ie, accidentally transmitted or iatrogenic CJD (iCJD); and variant CJD (vCJD). iCJD has been reported to be transmitted by neurosurgical instruments used on persons incubating or clinically presenting with CJD, by dura mater grafts, or by treatment with human pituitary hormones. While vCJD has been linked both to dietary exposure to bovine spongiform encephalopathy (BSE) and, more rarely, to transfusion of blood from infected donors, it has not been associated with either general or dental surgery (see reference Sc) of the normal prion protein (PrPC), both denoted in amyloid fibril protein nomenclature as APrP Sporadic Creutzfeldt-Jakob disease (sCJD) is the most frequent neurodegenerative condition among the rare human transmissible spongiform encephalopathies. It has an annual incidence of 1–2 per million and is found worldwide Sc bound to the surface of instruments reused during major surgical interventions may transmit CJD despite repeated cleaning and sterilization following previous prion-unaware protocols The cause of sCJD is still poorly understood. A number of studies report no association or report even protective effects of surgery, including neurosurgery , unmatched controls, and latency analysis The aim of the present study, pursuing the same line of investigation as two preceding reports The study was designed as a registry-based case-control study and has previously been described in detail elsewhere higher-risk and lower-risk SPs at the above lag (≥20 years). Conditional logistic regression was used to determine the odds ratio (OR) in three age strata defined by age at first-registered surgical discharge followed by the abovementioned ≥20-year lag, ie, <30, 30–39, and ≥40 years. Results were tabulated and, for purposes of interpretation, those for age-at-first-surgical-discharge strata were plotted on a graph which also showed published results of age-at-exposure assessments for iCJD and vCJD Our analysis was restricted to surgical interventions that were followed by long latency periods. Using the body-system classification of surgical procedures (SPs), exposure was defined as first major SP linked to a discharge preceding the clinical onset of illness for cases or the corresponding index date for controls (ID-2) by at least 20 years. We identified main surgical procedures, ie, those SPs remaining after excluding subsidiary procedures , see Scientific evaluation and preliminary ethical clearance of the research proposal was done by the EU Research Commission's “Concerted Action QLRG3-CT-2002-81223”. The study was formally notified to the Danish Data Protection Agency (record no. 2003-41-3104) and approved by the Karolinska Institute Ethics Committee  and "Regionala Etiskprövningsnämnden" dnr 04-171T 2004-04-29 1). Written consent was not given by patients for their information to be stored in the hospital data base and used for research since it was not needed. In Sweden, patients were never personally identified after register linkage took place by registries administrative officers. A data base was built after substituting at registries level each personal identification number by serial individual numbers. Data stored in official Swedish registries were used following legal regulations. The study conforms with Danish legislation requiring data management after notification to the Danish Data Protection Agency . According to the Danish legislation, there is no need for scientific-ethical clearance of registry based studies, nor is there a need for written consent by cases . Additionally all CJD patients had died by the time of data collection. No biological or tissue data was studied. The dataset is available on request to last author.higher- and lower-risk procedures were compared . The patterns obtained in our study suggest an increasing risk with decreasing age at first-registered surgery, particularly in the case of the <30-year age stratum. The ORs for each of three categories of age at first-registered surgery at a ≥20-year lag for main SPs, specified in This analysis included 123 study participants, made up of 33 cases, and 90 MCs with a record of surgery and documented age at discharge. The remaining 879 persons included in the database, 134 cases and 745 MCs, were free of such surgery. History of surgery followed by a ≥20-year lag was associated with significant excess risk of sCJD, with similar estimates for anatomically and etiologically classified SPs . For etiologically classified main SPs, with 5 exposed cases and 12 exposed MCs, mean age 28.5 years, the OR was 3.53 (95% CI 0.88–14.3). Mean ages for the lowest quintile were higher than for the corresponding <30-year group.This study represents the fourth sequential approach to quantifying associations between surgery and sCJD, using unique material and purpose-designed methods We found an age-at-exposure risk pattern which mimics that reported for vCJD. This is consistent with the possibility of an age-related common biologic-etiologic determinant of risk for different CJD forms, possibly neglected until now. This pattern is in agreement with the currently accepted notion of susceptibility, ie, different effects from a given exposure Attributing an age-at-exposure differential excess risk to age-at-exposure susceptibility would require that the nature of surgical exposure or preventive practices did not vary with age. The weight of reproductive surgery was similar across age groups. Additionally, excess risk of reproductive-organ surgery was similar to that seen for other types of surgery, such as gastrointestinal or orthopedic, at the same latency Age-related susceptibility to the effects of dietary exposure to BSE in the United Kingdom (UK) constitutes a key etiologic and epidemiologic feature of vCJD On the basis of the above limited, though detailed, data for iCJD, sCJD, and vCJD, a general model of age-related susceptibility to CJD could be hypothesized.A recent review of 18 case-control studies which examined links between medical procedures, particularly surgery and blood transfusion, and sCJD, identified many other associations, including protective ones, and highlighted diverse sources of potentially underlying bias high-risk procedures such as neurosurgery.We have previously estimated a population-attributable proportion of surgically transmitted sCJD in Denmark and Sweden of 18%. This estimate was based mainly on surgery performed on middle-aged and elderly patients Our results may imply that written recommendations for prevention, such as the need for single-use equipment, and for organizational measures may be particularly relevant for young surgical patients To sum up, the results of this study suggest that, in line with reported findings for iCJD and vCJD, there is an age-at-exposure-related susceptibility for risk of sCJD from routine surgery. This observation is relevant for epidemiologic research, clinical guidance to prevent CJD transmission in medical settings, and CJD surveillance.


Somatostatin has been extensively studied for the prophylaxis of pancreatitis following endoscopic retrograde cholangiopancreatography (ERCP). However, the results remain controversial. The present retrospective cohort study aimed to investigate the efficacy of pre- and post-ERCP somatostatin administration in the prevention of post-ERCP pancreatitis (PEP). All ERCP procedures performed at one hospital between January 2009 and December 2012 were reviewed. They were divided into three groups based on somatostatin administration: pre-ERCP som group , post-ERCP som group , and control group (no somatostatin administration). Out of a total of 304 cases, 81 received pre-ERCP somatostatin; 126 received post-ERCP somatostatin and 97 were not administered somatostatin. Pre-ERCP somatostatin was effective in reducing the incidence of PEP compared with that in the control group . This benefit was significant in high-risk patients , but not in low-risk patients . Post-ERCP somatostatin was not effective in preventing PEP in high- or low-risk patients. In conclusion, pre-ERCP somatostatin may be effective in reducing the risk of PEP in high-risk patients, but not in low-risk patients. Post-ERCP somatostatin did not reveal a benefit in high- or low-risk patients. However, large randomized controlled trials are required to further confirm these findings. Endoscopic retrograde cholangiopancreatography (ERCP) is a widely available and routine procedure for treating a wide variety of pancreaticobiliary diseases. Due to its advantage of being a minimally invasive treatment, it is generally accepted as a valuable and promising therapeutic modality, especially in choledocholithiasis . HoweverNumerous mechanisms have been proposed for the development of PEP . A commoNumerous methods, including ERCP techniques and pharmacological agents, have been introduced in an attempt to prevent PEP. Among the ERCP techniques, pancreatic duct stenting has been recommended to reduce PEP in high-risk patients . HoweverThe present retrospective cohort study was conducted to investigate the efficacy of pre- and post-ERCP somatostatin administration in the prevention of PEP.All ERCP procedures between January 2009 and December 2012 at the Sun Yat-Sen Memorial Hospital  were reviewed. Hospitalized patients who had undergone ERCP procedures were included in the current study. The exclusion criteria included: i) hyperamylasemia at the baseline blood test; ii) acute pancreatitis prior to ERCP; and iii) failed cannulation.Based on the different methods of somatostatin administration used at the hospital to prevent PEP, the patients were classified into the pre-ERCP som group, receiving somatostatin 1 h prior to ERCP by continuous intravenous infusion (0.25 mg/h) for 24 h; the post-ERCP som group, receiving somatostatin immediately following ERCP by continuous intravenous infusion (0.25 mg/h) for 24 h; and the control group, not receiving somatostatin administration. The patient demographics, indications, interventions, method of somatostatin administration and complications were noted for further analysis. Informed consent was obtained from the patients or the patients’ families. The present study was approved by the ethics committee of Sun Yat-Sen Memorial Hospital.All patients were fasted for 12 h prior to and at least 12 h following surgery. Intravenous sedation with meperidine and midazolam was given during the procedure. One dose of intravenous prophylactic antibiotic (cefoperazone 1 g) and proton pump inhibitor were given following the procedure. Selective cannulation of the common bile duct was attempted in all patients and pancreatic duct cannulation was attempted only if indicated. Sphincterotomy and therapeutic procedures including stone extraction  and bile duct stenting (plastic stent) were performed when indicated. All ERCP procedures carried out in the present study were performed by the same experienced endoscopist. A difficult cannulation was defined as ≥3 cannulation attempts. Details of the endoscopic procedure were recorded by the endoscopist immediately following the procedure.All patients remained in the hospital for ≥72 h following ERCP. Serum amylase levels were routinely measured prior to ERCP (baseline) and at 6 and 24 h following ERCP. Patients’ symptoms, including abdominal pain and tenderness, were also documented during the 24 h following ERCP.PEP was defined as new or worsened abdominal pain and tenderness persisting for >24 h following ERCP, with an elevated serum amylase level >3 times the normal upper limit. Based on previous studies, the severity of pancreatitis was classified as mild when the length of hospital stay was ≤3 nights, moderate when the hospital stay was 4–10 nights, and severe if >10 days of hospitalization, intensive care unit admission, or surgery were required for the pancreatitis . The lenFollowing careful consideration and discussion of various previous studies ,15, pati2 test (or Fisher’s exact test when appropriate). If a two-tailed P-value was <0.05 among the three groups, then further analysis was carried out to compare pre- or post-ERCP groups with the control group. Multivariate (logistic regression) analysis was also carried out to further confirm the effect of somatostatin on preventing PEP and to analyze the risk factors of PEP at the hospital. The data was analyzed with SPSS software version 13.0 . A two-tailed P-value <0.05 was considered to indicate a statistically significant results.Variables were reported using means (with standard deviations) and simple proportions. Analysis was performed using analysis of variance (ANOVA) and the χThere was a total of 343 ERCP cases from January 2009 to December 2012 at the hospital. Of these, 39 were excluded from further analysis: 25 due to serum amylase levels being higher than the normal upper limit prior to ERCP, 4 due to acute pancreatitis prior to ERCP and 10 due to failed cannulation. In the 304 enrolled cases, 81 cases received somatostatin 1 h prior to ERCP (pre-ERCP som group), 126 cases received somatostatin administration immediately following ERCP (post-ERCP som group) and the remaining 97 cases with no somatostatin administration were the control group.Among the 304 included ERCP cases, the overall incidences of PEP and hyperamylasemia were 12.8% (39/304) and 27.0% (82/304), respectively. Most PEP was mild and mild PEP occurred in 9.5% of cases. Moderate PEP occurred in 3.3% of cases . No severe PEP occurred. Statistical analysis revealed that the incidence of PEP in the pre-ERCP som group was significantly lower than that in control group  and 34.4% (55/160), respectively. The incidence of PEP in high-risk patients in the pre-ERCP som group was significantly lower than in high-risk patients in the control group  was carried out . Pre-ERCERCP is an effective and irreplaceable method for the diagnosis and treatment of pancreaticobiliary diseases. PEP is a common complication of ERCP with an incidence rate ranging from 1 to 15.1% of cases, which may increase to 30% in high-risk patients. Most PEP is relatively mild and the main consequence is prolonged hospital stay and increased healthcare expenditure. However, in rare cases (~0.3–0.6%) severe pancreatitis may be life threatening and have a devastating impact on the patient’s quality of life . ConsistWith many positive biological effects, including inhibition of exocrine pancreatic secretion, reduction of sphincter of Oddi contractions, modulation of the cytokine cascade and possible pancreatic acinar cytoprotection, somatostatin was believed to be one of the most promising drugs that could be used to reduce the risk of PEP –18. A meet al revealed that the incidence of PEP was significantly lower in the group with somatostatin administration immediately following diagnostic ERCP but prior to therapeutic ERCP, when compared with that in the placebo group   . Anothercing PEP . The reset al demonstrated that in patients undergoing ERCP for biliary ductal stones, precut sphincterotomy did not appear to be an independent risk factor for PEP  and procedure risk factors  . The pre for PEP . NeverthAlthough the present study revealed that pre-ERCP somatostatin administration was an effective method of reducing the risk of PEP whereas post-ERCP somatostatin administration was not, the results have limitations. Firstly, the data collection was retrospective. Although the primary factors associated with PEP were accurately collected, potential bias was inevitable. Secondly, all the data was collected from medical records which may have contained inaccurate information. However, since the method of somatostatin administration was a pivotal factor for its efficacy in preventing PEP, the current study revealed that somatostatin administration 1 h prior to ERCP of 0.25 mg/h for 24 h was effective in reducing PEP in high-risk patients, but not in low-risk patients.In conclusion, somatostatin administration prior to ERCP may be effective in reducing the risk of PEP in high-risk patients, but not in low-risk patients. Somatostatin administration immediately following ERCP did not demonstrate this benefit in either high- or low-risk patients. However, large RCTs are required in order to confirm these results.


It is still unclear whether carbohydrate consumption is associated with cardiovascular disease (CVD) risk. Genetic susceptibility might modify the associations between dietary intakes and disease risk.The aim was to examine the association between the consumption of carbohydrate-rich foods  and the risk of incident ischemic CVD , and whether these associations differ depending on genetic susceptibility to dyslipidemia.Among 26,445 individuals  from the Malmö Diet and Cancer Study cohort, 2,921 experienced an iCVD event during a mean follow-up time of 14 years. At baseline, dietary data were collected using a modified diet history method, and clinical risk factors were measured in 4,535 subjects. We combined 80 validated genetic variants associated with triglycerides and HDL-C or LDL-C, into genetic risk scores and examined the interactions between dietary intakes and genetic risk scores on the incidence of iCVD.Subjects in the highest intake quintile for whole grains had a 13%  lower risk for iCVD compared to the lowest quintile. A higher consumption of foods rich in added sugar  had a significant cross-sectional association with higher triglyceride concentrations and lower HDL-C concentrations. A stronger positive association between a high consumption of sugar and sweets on iCVD risk was observed among those with low genetic risk score for triglycerides (p-interaction=0.05).In this prospective cohort study that examined food sources of carbohydrates, individuals with a high consumption of whole grains had a decreased risk of iCVD. No convincing evidence of an interaction between genetic susceptibility for dyslipidemia, measured as genetic risk scores of dyslipidemia-associated variants, and the consumption of carbohydrate-rich foods on iCVD risk was observed. It is still unclear whether carbohydrate consumption is associated with cardiovascular disease (CVD) risk. Evidence suggests that carbohydrate quality is more important than carbohydrate quantity, and that in addition to macronutrients it is important to examine foods rich in carbohydrates. For example, whole grains are related to a decreased risk of CVD , 2, wherThe Malmö Diet and Cancer Study (MDCS) is a prospective population-based cohort with baseline examinations conducted between 1991 and 1996. All men born between 1923 and 1945 and women born between 1923 and 1950 that live in Malmö were invited via personal letters and advertisements in the local newspaper and public places to participate in the study. Limited Swedish language skills and mental incapacity were the only exclusion criteria. The participation rate was approximately 40% . The ethUsual dietary intakes were estimated using a modified diet history method specifically developed for MDCS . InformaThe nutrients examined in this study were: total carbohydrates, sucrose and dietary fiber. The foods examined were selected for being significant sources of dietary carbohydrates: vegetables (g/day), fruits and berries (g/day), juice (g/day), potatoes (g/day), whole grains , refined grains , cookies and cakes (g/day), sugar and sweets (g/day), and sugar-sweetened beverages (g/day). Milk, which is also a significant source of carbohydrates, has already been examined in relation to iCVD risk within MDCS and therefore was not included in this study . The nutIncident CVD events were identified by linkage to the Swedish Hospital Discharge Registry and Cause-of-death Registry . Stroke LPA rs1084651, JMJD1C rs10761731 and NPC1L1 rs217386 because of difficulties in genotyping or no proxies were available. SNPs were then excluded in the current study if the success rate was less than 90%  or if the Hardy-Weinberg equilibrium p-value was less than 0.00057 (0.05/87) . Weighted genetic risk scores were constructed using PLINK (version 1.07) for triglycerides (26 SNPs), HDL-C (41 SNPs) and LDL-C (32 SNPs) by multiplying the effect size (β-coefficients) found in the meta-analysis [Genotyping was performed at the Clinical Research Centre, Malmö, Sweden, by using the Sequenom MassARRAY  or Taqman allelic discrimination on an ABI 7900 . We estimated susceptibility for dyslipidemia by combining the validated single-nucleotide polymorphisms (SNP) reported in the genome-wide association meta-analysis by Teslovich et al. . We geno2) was calculated from direct measurements of weight and height. Subjects, wearing light clothing and no shoes, were weighed using a balance-beam scale for weight and a fixed stadiometer for height (cm). Smoking habits were categorized into smokers, ex-smokers and never smokers. Alcohol consumption was categorized into six categories. Individuals indicating no consumption during the past year and no consumption in the 7-day food diary were categorized as zero-consumers. The other individuals were divided into gender-specific quintiles based on their consumption in the food diary. Education level was divided into elementary, primary and secondary, upper secondary, further education without a degree, and university degree. Leisure-time physical activity was obtained from the questionnaire where the individuals had to estimate minutes per week they spent on 17 different activities. A score was constructed taking into account the intensity and duration of the activity; the score was divided into quintiles. Non-adequate reporters of energy were determined by comparing their reported energy intake with their total energy expenditure . Individuals with reported energy intake above or below the 95% confidence interval for total energy expenditure were categorized as “misreporters”. Individuals answering yes to the questionnaire item “Have you substantially changed your dietary habits in the past?” were classified as “dietary changers”.Body mass index  was used for all statistical analyses. Baseline characteristics according to incident iCVD status were examined using general linear model adjusted for age and sex. The mean age, BMI and dietary intakes of the lowest and highest intake groups in the food categories (quintiles or zero-consumers/tertiles) were reported separately for men and women. We also examined the linear relationship between the intake of food group categories and possible mediating risk factors between dietary intake and iCVD risk  among the 4535 individuals with complete data on all risk factors and the variables that were adjusted for . Blood pressure analyses were also adjusted for the use of anti-hypertensive drugs, and blood lipid and lipoprotein analyses were also adjusted for the use of lipid-lowering drugs. We used ln-transformed risk factor variables to test for trend across food group categories. In sensitivity analyses, we excluded individuals categorized as misreporters of energy intake .Cox proportional hazard regression analysis was used to calculate hazard ratios for iCVD with the lowest food category (lowest quintile) as the reference, and with person-years of follow-up as the underlying time-variable. The proportional hazards assumption was checked graphically using log minus-log survival plot and tested using Shoenfeld residuals. These analyses were adjusted for age, sex, season of data collection, diet method version, total energy intake, and several potential confounders . These covariates were selected a priori for being known risk factors for CVD and for being associated with dietary habits, without being considered intermediates between dietary habits and disease. If values for any of the categorical variables were missing, they were treated as a separate category . If values for the continuous variables were missing, they were excluded . To examine the heterogeneity of effect in men and women we included the cross product of sex and diet exposure in the analyses. Because BMI can be regarded as a mediating factor, we also performed the analyses without BMI as a covariate in the multivariable model. In additional analyses, other dietary factors  were included as covariates, because these dietary factors have previously been associated with iCVD risk and could confound the examined associations , 20. We We examined whether the associations between dietary intakes and iCVD risk were different depending on genetic risk scores for triglycerides, HDL-C and LDL-C. The interactions between dietary intakes and risk scores were examined by including a cross product of the continuous variables (diet categories x genetic risk score) in the multivariable model in addition to the main variables.The baseline characteristics of incident iCVD cases and non-cases are shown in -11). A higher consumption of foods rich in added sugar  was significantly associated with higher triglyceride concentrations and lower HDL-C concentrations. Specifically, mean triglyceride concentration in the highest vs. lowest quintile of sugar and sweets and sugar-sweetened beverages were 1.32/1.23 (p-trend = 0.007) and 1.37/1.25 (p-trend = 5 x 10-6), respectively, and mean HDL-C were 1.36/1.43 (p-trend = 3 x 10-5) and 1.35/1.41 (p-trend = 1 x 10-4), respectively. Sugar-sweetened beverage consumption was associated with higher insulin resistance (measured by HOMA-IR), while a high consumption of fiber, vegetables, and fruits and berries was associated with lower insulin resistance. Generally, the exclusion of misreporters produced stronger risk estimates. However, the results of the sensitivity analysis would not change our interpretation of the data and are therefore not shown.The cross-sectional associations between food intakes and blood pressure, blood lipids and lipoproteins, and HOMA-IR were investigated among 4,535 individuals at baseline . Total cWe observed similar incidence rates of iCVD in the highest vs. lowest quintiles of total carbohydrates (8.2 vs. 8.4 cases/1000 person-years). In the basic model, sucrose consumption was positively associated with iCVD risk, while the consumption of fiber, vegetables, fruits and berries, juice, whole grains, and cookies and cakes was negatively associated with iCVD risk. When we adjusted for several lifestyle factors, only higher consumption of fiber and whole grains remained statistically significantly associated with a decreased risk of iCVD . In the -48), HDL-C (p = 7x10-62), and LDL-C (p = 2x10-76). The genetic risk scores for LDL-C and HDL-C were significantly associated with incidence of iCVD , while the genetic risk score for triglycerides was not associated with iCVD (p = 0.13). Only one of the examined dietary variables showed nominal significant interaction with at least one of the genetic risk scores , the socio-demographic structure, and the prevalence of obesity and smoking were similar . In addiIn this study, we accounted for genetic susceptibility to dyslipidemia by combining 80 validated genetic variants associated with blood lipids and lipoproteins. Together, these variants have been estimated to account for 25–30% of the genetic variance in blood lipid and lipoprotein levels in Caucasians and can be used as an estimate of the overall genetic susceptibility to dyslipidemia. However, these genetic variants are associated with different mechanisms of lipid and lipoprotein metabolism. By combining such different mechanisms, we may end up neutralizing the possible interacting effects due to the different directions of the interactions by the individual genetic markers. Thus, we found no convincing evidence that the combined genetic risk score of 80 common variants associated with dyslipidemia would modify the association between dietary intakes of carbohydrate-rich foods and iCVD risk, particularly if we corrected the p-values for multiple tests. Future studies may need to examine genetic variants affecting specific mechanisms and pathways separately, to address whether genetic susceptibility affecting specific mechanisms or pathways would modify the effect of dietary intakes on iCVD risk. Few earlier studies have combined individual SNPs into genetic risk scores and examined their interaction with lifestyle factors . Pollin In conclusion, the results from the present study indicate that, among the food sources of carbohydrates, whole grain consumption affords the highest protection against iCVD. In addition, we found no convincing evidence that susceptibility to dyslipidemia, estimated as a genetic risk score of 80 validated genetic variants, modifies the association between these foods and iCVD risk.S1 Table(DOC)Click here for additional data file.S2 Table(DOC)Click here for additional data file.S3 Table(DOC)Click here for additional data file.S4 Table(DOC)Click here for additional data file.


The objective of this study was to compare in-hospital deaths and length of stays for diabetes-related preventable hospitalizations (D-RPHs) in Hawai‘i for Asian American, Pacific Islander, and white Medicare recipients aged 65 years or older.International Classification of Diseases – 9th Revision (ICD-9) codes to identify D-RPHs as defined by the Agency for Healthcare Research and Quality. Length of stays and deaths during hospitalization were compared for Asian American and Pacific Islander versus whites in multivariable regression models, adjusting for age, sex, location of residence , and comorbidity.We considered all hospitalizations of older (>65 years) Japanese, Chinese, Native Hawaiians, Filipinos, and whites living in Hawai‘i with Medicare as the primary insurer from December 2006 through December 2010 . We used Among the group studied, 1,700 hospitalizations of 1,424 patients were D-RPHs. Native Hawaiians were significantly more likely to die during a D-RPH  than whites. Filipinos had a significantly shorter length of stay  for D-RPH than whites. Among Native Hawaiians with a D-RPH, 59% were in the youngest age group (65–75 y) whereas only 6.3% were in the oldest (≥85 y). By contrast, 23.2% of Japanese were in the youngest age group, and 32.2% were in the oldest.This statewide study found significant differences in the clinical characteristics and outcomes of D-RPHs for Asian American and Pacific Islanders in Hawai‘i. Native Hawaiians were more likely to die during a D-RPH and were hospitalized at a younger age for a D-RPH than other studied racial/ethnic groups. Focused interventions targeting Native Hawaiians are needed to avoid these outcomes. Diabetes rates are higher among many Asian American and Pacific Islander populations than among whites . Native Hospitalizations are an important area of focus in diabetes care because they account for a major portion of health care cost ,7 and arAmong Hawaiian residents aged 65 years or older, Native Hawaiians and some Asian groups are significantly more likely to have D-RPHs, even after considering the high diabetes prevalence rates in these racial/ethnic groups . HoweverHawai‘i provides excellent opportunities to research D-RPHs. Hawai‘i has a large population of older adults , growingInternational Classification of Diseases – 9th Revision – Clinical Modification (ICD-9) codes  is an independent, not-for-profit health care data organization that collects and validates detailed inpatient discharge data at the patient level from all hospitalizations by all insurers in the state. HHIC data include information on race/ethnicity of patients, insurer, age, sex, and 9) codes . Patient9) codes , an indihttp://www.qualityindicators.ahrq.gov/Downloads/Modules/PQI/V31/pqi_guide_v31.pdf). Although people with a potentially preventable hospitalization for short-term or long-term diabetes care may have had uncontrolled diabetes in the past, there is no overlap by AHRQ definitions of preventable hospitalizations for uncontrolled diabetes and potentially preventable hospitalizations for short-term and long-term diabetes complications.Following AHRQ definitions, we used ICD-9 discharge codes to identify D-RPH . We inclThe HHIC race/ethnicity variable is created from the categories available consistently across all hospitals in Hawai‘i from December 2006 to December 2010 . One priThe dependent variable, death during stay, was identified from the hospital record’s discharge disposition as “expired.” Length of stay was measured by the total number of days of each potentially preventable hospitalization. We controlled for sex on the basis of administrative data and for 3 age categories . We also controlled for comorbidities as measured by the Charlson Comorbidity Index (CCI) . The CCI2 and a multivariable logistic model. Length of stay was compared by race/ethnicity by using all hospitalizations rather than unique patients. A repeated measure, negative binomial regression model, was used to address potential correlation within patients in these analyses as these were not restricted to one hospitalization per patient.Death during stay and length of stay were compared across Asian American and Pacific Islander subgroups and whites in unadjusted analyses and analyses were adjusted for age, sex, location of residence, and comorbidity. After identifying patients across all hospitals using the HHIC data, we included only 1 hospitalization per patient for the analyses of in-hospital death. From these unique patients, we compared the likelihood of in-hospital death during a preventable hospitalization by race/ethnicity by using χWe found 1,700 D-RPHs during the study period by 1,424 unique patients. Significant differences were seen across racial/ethnic groups for many clinical characteristics . D-RPHs In unadjusted outcome variables, Native Hawaiians with a D-RPH had the longest average lengths of stay, followed by whites and Chinese. There were 53 deaths total in our study group. Seven percent of D-RPH among Native Hawaiians ended in death compared with 3.1% of D-RPHs among Japanese. D-RPHs by Native Hawaiians also had the highest comorbidity scores, with the average CCI score 2 points higher than the CCI scores for Japanese D-RPHs, 1.8 points higher than for Chinese D-RPHs, and 1.4 points higher than for Filipino D-RPHs.Multivariable models show predictions of length of stay and death during stay by race/ethnicity after adjusting for comorbidity, age, sex, and living on Oahu . CompareTo provide insight into our study findings, we also considered the frequencies of specific D-RPHs by racial/ethnic group . The mosThis statewide study found significant differences in the clinical characteristics and outcomes of D-RPHs for Asian American and Pacific Islander groups. Disparities were seen particularly for Native Hawaiians, who were more likely to die during a D-RPH and were hospitalized at younger ages for a D-RPH than other studied racial/ethnic groups. D-RPHs of Native Hawaiians were more likely to involve an amputation, which was the most expensive of the 4 types of D-RPHs encountered in previous research .A primary value of this research is to demonstrate the depth and impact of diabetes-related disparities for Native Hawaiians. Previous studies have found that Native Hawaiians aged 65 years or older are not only diagnosed with diabetes at higher rates than other populations in Hawai‘i  but are Our findings may also be useful for community health centers and other organizations providing comprehensive, preventive services to help underscore the importance of strong chronic disease care management. Patients may also be interested in knowing of the apparent inequity in Native Hawaiian deaths during D-RPHs to underscore the importance of both condition management and promptly seeking treatment when an urgent condition  arises.A previous study found that older Japanese, Filipino, and Chinese adult populations were also more likely to be hospitalized for a D-RPH  than older white adults . HoweverOur findings of health care disparities among Native Hawaiian D-RPHs are of interest because our study focuses on residents of Hawai‘i covered by Medicare. A uniform payer, such as Medicare, could potentially reduce disparities in outcomes. Other evidence suggests that even as a uniform payer, Medicare does not resolve disparities between Asian Americans and Pacific Islanders and whites in quality of care . For insWe did not find significantly longer lengths of stay for D-RPHs among Asian and Pacific Islander groups than among whites. Instead, we that found Filipinos had significantly shorter lengths of stay for D-RPHs. Longer lengths of stay may signify more complications or greater danger for hospital-associated adverse events. On the other hand, shorter lengths of stay may be associated with more adverse events following discharge . This woWe also found differences in clinical characteristics across groups that could inform the design and focus of interventions. Even among an older population, Native Hawaiians experienced a D-RPH at a younger age than other racial/ethnic groups studied. These findings are consistent with previous research  and are Although this study has numerous strengths, including 4 years of data from a large, statewide sample and representation of diverse Asian American and Pacific Islander groups, the study has some limitations. These data do not provide information on many factors that might be useful to explain or better understand health disparities among racial/ethnic groups, particularly some clinical factors such as depression and social determinants such as familial support. We were unable to consider factors such as obesity, time since diagnosis, education, or proximity to primary care –29. We wEfforts of the Centers for Medicare and Medicaid Services to address disparities have not traditionally focused on Asian Americans and Pacific Islanders . Yet est


Background. We tested an original, woman-focused intervention, based on body empowerment, and female-initiated barrier methods, including the female condom (FC) and cervical barriers. Methods. Eligible women were >= 18 years of age, HIV seronegative, and active drug users, reporting 30% or greater unprotected sex acts. Both controls (C) and intervention (I) participants received enhanced HIV/STI harm reduction counseling. I participants underwent 5 additional weekly group sessions. We compared change in frequency of unprotected vaginal intercourse across arms at 12 months. Results. Among 198 enrolled women, over 95% completed followup. Two-thirds were African-American; most of them used crack, had a primary partner, and reported sex exchange. In paired t-tests from baseline to followup, the frequency of unprotected vaginal sex dropped significantly for I  and C  arms with all partners. The difference in change across arms was of borderline significance for primary partner (P = 0.075); no difference was seen for nonprimary partner (P = 0.8). Use of male condom and FC increased with both partner types over time, but more consistently among I women. Conclusion: The “value-added” impact of the intervention was observed mainly with primary partners. Body knowledge with routine FC counseling should be incorporated into interventions for drug-using women. Women have among the highest rates of new HIV infections globally and the rate of new infections has not lessened in recent years –4. AfricCrack-using African-American women are a distinct, hard-to-reach population for whom empowerment to reduce HIV/STI risk takes on additional complexities due to the entangled dependencies of drugs, partnerships with men (who are often drug involved) for material support for women and their children, and constant threat of violent reprisal , 7–9. CoWomen's biological inequality in vulnerability to sexually transmitted infection (STI) can be addressed with greater availability and use of male and female condoms (FC). In addition to challenges in the diffusion of available protection technologies, however, gender inequity in sexual relationships, limited bargaining power of women complicated by threats of violence, and insufficient resource commitment to health issues among minorities and the poor all contribute to women's continuing entrenchment of HIV/AIDS in the United States.The FC is the only female-initiated protection method that protects against HIV/STI and unwanted pregnancy at a level equivalent to a male condom . Full iEffective interventions targeted to drug-using women to reduce sexual risk are few in number and, as pointed out by Wechsberg et al. , have ra The Womens' Co-Op Intervention is a brief 4-session intervention with mixed individual and group sessions, based on empowerment and feminist theory, encouraging women to understand their HIV risks in the context of substance abuse and effects on personal power and vulnerability to victimization . NumerouSterk and colleagues  followed“BestBET”) integrated elements from three existing theories—the Theory of Gender and Power [Our Bodies, Ourselves [The behavioral intervention tested here  from a sample of 198 drug-using women with high-risk sexual behavior who were followed for 12 months.The feminist health model as applied to HIV underscores the need for holistic education about reproductive organs and genitals, rather than a narrow focus on HIV. Our intervention included session content on normal female anatomy, the menstrual cycle, pregnancy, menopause, STI signs and symptoms, female cancers, benefits of screening (mammography and pap smear), and common surgeries. The body empowerment approach posits that increased knowledge, sense of ownership, and pride in the body (“body knowledge”) are an independent pathway to self-esteem and to self-efficacy for protection behavior—use of female-initiated barriers, MC negotiation with partners, and refusal of unsafe sex. Thus, we introduced to intervention women the entire range of female methods thought possibly to reduce risk of STI/HIV—female condom, diaphragm, cervical cap, and spermicides  including a module on basic self-defense techniques and exit strategies and use of protection methods in the context of forced sex. The intervention was held at a university-operated, community storefront site with a long history of provision of HIV counseling and testing in a poor, inner city neighborhood. The intervention was culturally specific and woman focused. The elements of the intervention were (1) small groups with interactive counseling; (2) trained and certified near-peer community counselors with a history of substance abuse and in recovery for at least 2 years; (3) role play and rehearsal, (4) multimedia educational approaches, such as videos, audio tapes, brochures, posters, and anatomical models; (5) active referrals to local service organizations; (6) access to HIV testing; and (7) training of CBO staff for community capacity building. Audio tapes of diverse risk vignettes based on interviews with the target population and accompanying illustrated handouts were prepared by an outside nonprofit health organization. We collaborated with a nearby branch of a national family planning organization to facilitate diaphragm and cervical cap fittings and offered patient advocate support to accompany study participants to clinic appointments.To be eligible for the BestBET study, we required women to (1) be 18 years of age or older, (2) be HIV seronegative, (3) report 30% or more unprotected vaginal or anal sex acts over the preceding three months , (4) report not currently being in drug user treatment other than with Methadone, and (5) report that heroin or cocaine were either injected, snorted, or smoked at least 12 times during the same three-month interval. HIV serostatus was determined using ELISA with confirmatory Western Blot. Women were excluded for psychiatric problems or if they had been in drug treatment for more than 6 months. Because changing drug use behavior was not an explicit study objective, we did not exclude women from attending sessions if they were “high” except if such use disrupted group dynamics.Eligible women were recruited in Philadelphia between November 2001 and August 2003, with the use of a mobile outreach van staffed with trained interviewers and harm reduction counselors. The van was parked in designated, high-risk areas known for crack-selling and smoking activity. Interested women gave the first written consent to be administered a 20-minute, confidential prescreening assessment interview that included demographic and behavioral risk items as well as to provide locator information. The second screening assessment was conducted at a community storefront site that served as an information and referral center for drug users. Potential participants completed a second written informed consent procedure for the full study. Study compensation for each visit was $25. Recruitment and study methods have, in part, been presented in a prior publication .This study was approved by and conducted in compliance with the Institutional Review Board of the University of Pennsylvania. All enrolled women provided written informed consent.Participants completed a baseline risk assessment instrument delivered via audio, computer-assisted self-interview (a-CASI) targeting sexual and drug user behavior over prior 6 months. Partner types were divided into primary and nonprimary. Additional baseline data were collected in a face-to-face interview including the following: demographic and reproductive health history, history of STI, health care insurance, and types and location of health care services used in past 6 months. A knowledge quiz on the reproductive system and disease prevention methods was also administered .Following baseline data collection, all women received enhanced HIV and STI harm-reduction counseling that exceeds standard guidelines for HIV voluntary counseling and testing (VCT); both the MC and FC were taught. Participants then underwent testing for HIV/STI. At the posttest session, we randomized HIV-negative women to intervention or control group. We counseled women with STI on treatment locations and required these women to bring written confirmation of treatment for formal enrollment. We provided HIV-positive women with referrals for further counseling and care but they were excluded from this study.Women randomized to the intervention arm were invited back for five, 3-hour, weekly group sessions within 2 months of enrollment and were contacted for 6- and 12-month reunion sessions at community sites. Control participants received limited case management and the offer of free MCs and FCs, but no other proactive study intervention. At 6- and 12-month following enrollment, all assessments were repeated at the community sites or other locations when necessary.Masters' level interviewers were trained and certified in VCT and in standardized interviewing techniques. Participant contact information was updated at least quarterly. Intensive retention efforts  were used to follow participants considering their mobility, including community outreach, visits to known crack houses and other hang-outs, and hospital and prison outreach. Retention challenges were discussed weekly in study meetings. Using multiple methods and extensive efforts to locate hard-to-reach participants, the retention rate was 95% at 12 months.t-test for continuous variables were conducted for demographic variables and background characteristics. Univariate analyses including frequencies and percentages were completed to describe the total sample and its subsets at baseline and 12-month follow-up. To test for differences between the control and intervention groups at baseline, chi-square for dichotomous variables and independent sample Our main outcome variable, frequency of unprotected vaginal intercourse (monthly), is the focus of this paper. Data for this analysis were derived from a series of questions delivered via a-CASI, asking first, the total frequency of acts during the interval  followed by the frequency of acts protected by MC or FC, diaphragm, cervical cap, or spermicide . The remainder was defined as unprotected vaginal sex acts. Protected and unprotected vaginal sexual acts were calculated at baseline and at 12-month followup for two types of partners: primary partners and HIV-negative nonprimary partners. The number of HIV-positive nonprimary partners was prohibitively small to include for analysis. A primary  partner was described as “someone you have lived with or have seen a lot, and to whom you have felt a special emotional commitment.” nonprimary partners were defined as “other male partner(s) (not your primary or main partner).” If a woman answered that she did not have vaginal sex in the prior interval (this was only possible at followup) or did not have that type of partner, she was considered as having zero frequency of unprotected acts. For this study we used an intent-to-treat analysis with the inclusion of women who may not have been sexually active during followup and/or may not have had a primary or nonprimary sexual partner.t-test (P < 0.05 was considered significant). For comparison of intervention versus control arms, first a “change” variable was calculated in the mean frequency of unprotected acts between baseline and followup. The change was then compared across arms. Either parametric (Student's t-test) or nonparametric tests (Mann-Whitney U test) were used to assess statistical significance, depending on the normality of distribution. All analyses were conducted using SPSS version 19.0 .Pairwise analysis was performed on the outcome variable separately for primary and nonprimary partners from baseline to followup, for each intervention arm, which included generating a paired sampled n = 304), six percent were HIV positive, and overall STI prevalence was 49% [A total of 1134 women were prescreened at the van. Of the 616 eligible women, 304 (49%) successfully completed the baseline interviews and specimen collection and were invited to participate in the BestBET study. Among eligible women completing baseline interviews  had a primary male sex partner, and more than half  had both a recent nonprimary male sex partner(s) and a primary partner. Women with primary partners reported substantial levels of recent (past 6 months) intimate partner violence: 21% had partners who had made threats on their life, 34% had been forced to have vaginal or anal sex without a condom, 25% had been punched or hit with something that hurt, and 11% had consulted medical care because of a fight (data not shown). No significant differences across arms were found.At baseline, the overall mean frequency of unprotected vaginal sex acts  with primary partners in the past 6 months was 34.3 (median = 12), and with nonprimary, HIV-negative partners was 22.7 acts (median 0). At 12-month followup, the overall mean frequency of unprotected vaginal sex acts  with primary partners was 15. 6 (median 0); with nonprimary HIV-negative partners the follow-up mean frequency was 2.9 acts (median 0). A total of 189 women completed assessments at 12-month followup (retention rate: 95.4%). controls, for primary partner, baseline frequency was 32.7 acts; at 12 months this was reduced to 19.3 acts .For the paired baseline-to-followup comparisons, among control women with nonprimary HIV partners, mean baseline frequency of unprotected vaginal acts was 21.6 acts; at 12-month followup frequency was 2.5 . Among intervention women, frequency of unprotected vaginal acts with non- primary HIV-partners at baseline was 23.8, and at 12-month followup was 3.5 .For P = 0.075), favoring the intervention arm. For nonprimary partners, no statistical difference could be detected between the change observed across the two arms from baseline to followup (P = 0.80).A statistical test of the change over time , per partner type, compared across arms, indicated borderline significance for primary partners  as well as postexposure prophylaxis (PEP) now documented to be valuable tools in the prevention mix and potentially applicable to drug-using populations . The pot


Cardiac resynchronization therapy (CRT) has become an important pillar of contemporary heart failure therapy. The efficacy of CRT, however, critically relies on proper LV lead placement and performance, which is why data regarding the long-term performance of CS leads are of considerable interest. Available studies are limited by a restricted variety of lead vendors, earlier lead models and / or very short follow-up periods. In the current study, we therefore investigated the long-term performance of modern LV leads in a large "real world" cohort of patients undergoing CRT implantation.All 193 patients who had successfullyundergone CRT implantation at the University Hospital Zurich between September 2003 and January 2010 were included in the study. An overall stable course of stimulation energy was observed over time; neither ischemic etiology, lead configuration, or severely reduced EF had an influence on the evolution of energy thresholds over time. Interestingly, patients with a high energy threshold at baseline experienced a significant reduction during follow-up. In contrast, a significant drop in impedance was seen following implantation, followed by a steady course for the rest of the observation period. Only 15 patients (9.7%) showed an impedance > 1000 Ohm at any time during their follow-up. Seven lead dislocations were observed during follow up.The current comprehensive analysis of long-term performance of modern coronary sinus leads demonstrates excellent stability, performance and safety. These data may have important implications for physicians involved in biventricular pacemaker implantations and in the follow-up care of these patients. Cardiac resynchronization therapy (CRT) has become an important pillar of contemporary heart failure therapy due to the impressive reduction in morbidity and mortality observed in large-scale clinical trials -3. SeverThe efficacy of biventricular pacing critically relies on proper LV lead placement and performance. The former, however, is not infrequently challenging; indeed, lead placement at anatomically optimal sites for effective LV resynchronization sometimes requires accepting high capture thresholds due to suboptimal lead contact or presence of scar tissue. As such, the possibility of late lead failure due to rising thresholds, increased battery drain,and, eventually even loss of biventricular pacing is of concern. Data regarding the long-term performance of CS leads, especially in relation to baseline characteristics at the time of implantation, are therefore of considerable interest. So far, few studies have investigated the behavior of LV leads in CRT patients; moreover, these series were limited by a restricted variety of lead vendors, earlier lead models and / or very short follow-up periods -10. In tAll 193 patients who had undergone successful CRT implantation including placement of a coronary sinus left ventricular lead at the University Hospital Zurich between September 2003 and January 2010 were included in the study (patients implanted by J.H. and D.H.). Patients in whom transvenous LV lead placement was not possible as well as patients with epicardial LV leads were excluded from the study. For analyses of follow-up parameters, patient files at our pacemaker clinic were reviewed.Biventricular pacemakers / ICDs and leads from Biotronik, Guidant / Boston Scientific, Medtronic and St. Jude Medical were implanted . The impLV lead measurements at implantation were taken in the operating room following successful lead placement. Baseline measurements were taken prior to hospital discharge (one day following device implantation in most patients). Further measurements were recorded when patients presented for scheduled follow-up visits to our pacemaker clinic or in case of unplanned consultations.Statistical analyses were performed using SPSS 17.0  and GraphPad Prism 4.0 . Unpaired continuous and categorical variables were compared using Student's t-test and Chi-square test, respectively. Intraindividual development of variables  were compared using paired Student's t-test. Comparisons of > 2 groups were performed using an ANOVA test with Bonferroni correction in case of significant results. A p-value < 0.05 was considered significant.Baseline clinical, echocardiographic and implantation characteristics are summarized in Median follow-up of all patients with at least one follow-up visit at our center was 24 months. The evolution of coronary lead stimulation energy threshold, impedance and R-wave sensing is shown in Selected subgroup comparisons of energy threshold, impedance, and R-wave sensing at baseline (pre-discharge) and during follow-up (12-15 months) are shown in Overall, no significant difference in average energy threshold was observed during 1-year follow-up as compared to baseline . NeitherOverall, 67 patients (35.4%) had a high LV lead threshold at implantation, which was particularly prevalent in patients with an LV scar . During follow-up, 22% of patients (33/152) had a very high maximal LV threshold (defined as > 3μJ). Patients with a threshold > 1μJ at implantation had a higher chance of going on to a threshold ≥ 3μJ at any time during follow up as compared to patients with a threshold < 1μJ .During follow-up, no significant change in impedance from pre-discharge values was observed for the overall cohort (Tab. 2). As expected, impedance was higher in bipolar leads, which did not change during follow up. Also patients with a low EF (< 30%) demonstrated slightly lower LV lead impedance. Other baseline characteristics including coronary heart disease, gender,lead configuration, and LV scar did not significantly affect LV lead impedance at baseline or at follow-up.Patients with impedance values > 1000 Ohm at the time of implantation experienced a significant drop until the time of hospital discharge . Indeed,On average, left ventricular R-wave sensing improved slightly during follow up . This was particularly pronounced in patients with non-ischemic heart disease, in those with a bipolar lead, and in those with no scar or a scar outside the prime target region for LV lead placement .A total of 7 cases of LV-lead dislocations (3.6%) were observed during follow-up. The median time to dislocation was 111 days (range 10 - 283 days). Six cases were macro-dislocations necessitating lead revision. In one case a micro-dislocation leading to considerably elevated stimulation thresholds was observed, which was managed conservatively . No significant adverse events, including arrhythmic events, were observed as a result of dislocated leads.Optimal lead placement is of paramount importance for a favorable outcome in CRT  Indeed, Our current comprehensive analysis of the long-term behavior of modern coronary sinus leads provides several findings which may be of value for physicians implanting and/or managing patients with CRT devices. We demonstrate that most patients with a high energy threshold during implantation normalize over time, while a third (34%) increases to very high levels. Neither ischemic etiology, lead configuration, severely reduced EF nor presence of a scar had a significant influence on the future development of energy thresholds. This is in contrast to previous studies, in which a pronounced increase over time was observed in particular in patients with unipolar leads  In the lSimilar to the capture thresholds, high impedance values at implantation normalized in most patients (82%) during the ensuing hours to days, and only a minority increased to higher levels over time. These findings indicate that in an anatomically optimal position, the mere presence of an elevated impedance  should not in itself prompt for lead relocation to a potentially less suitable LV pacing site. Indeed, no baseline variables including the presence of coronary heart disease, lead configuration, and LV scar were predictive of an elevated LV lead impedance at baseline or during follow-up. As expected, LV lead impedance was slightly higher in bipolar leads, which did not change during follow up. There was no difference between the leads of different manufacturers.A small but significant increase in LV sensing values was observed during follow-up, which was most pronounced in patients with non-ischemic cardiomyopathy, bipolar leads, and better (> 30%) LV ejection fraction. In contrast, and as expected, R-wave sensing decreased in the case of scar tissue in the target area of LV lead implantation . In CRT, LV sensing is considered of minor value, as ventricular sensing is usually performed via the right ventricular electrode, in particular in CRT-ICD devices. However, our data on the development of LV sensing values confirm the overall stable course indicated by stable capture thresholds and impedance values of modern LV leads, potentially providing an option as primary pacing leads .In contrast to right ventricular pacing leads, LV leads typically do not have a fixation mechanism (screw/tines) but are passively held in place making them more prone to dislocation, which may result in alterations in pacing parameters. In general, elevated pacing thresholds result in faster battery depletion, leading to more frequent device replacements  as well as increased costs. While the limited amount of patients with very long-term follow-up (i.e. until the time of generator exchange) precluded a meaningful and comprehensive analysis in this regard, elevated LV thresholds will likely be associated with earlier battery depletion also in our cohort. Overall, only 7 lead dislocations (3.6%) were observed during the follow-up in our cohort (6 of which necessitated lead revision),comparable to the recent Euroheart Survey, highlighting the excellent stability, performance and safety of today's LV leads  In one cOur study is limited by its retrospective design; as such, capture thresholds were measured at varying pulse width, for which we corrected by calculation of stimulation energy thresholds. Although this may render direct transferability of our data difficult, it represented the only valid way to account for these inherent differences. Further limitations include the fact that leads from one vendor (Guidant / Boston Scientific) were only used in a minority of patients.The current comprehensive analysis of the long-term performance of modern coronary sinus leads revealed a stable course of these leads over time. An elevated energy capture threshold at implantation was associated with an increased likelihood of proceeding to very high thresholds during follow-up, which was the case in 34% of these patients. These data may have important implications for physicians involved in biventricular pacemaker implantations and in the follow-up care of these patients.