Long-term cost and complications of surgery in patients with ulcerative colitis: a claims data analysis.

OBJECTIVES: Use claims data to assess healthcare resource utilization (HCRU) and cost for patients with ulcerative colitis (UC) who had surgery and patients who did not. METHODS: UC patients from a German health insurance were included between 01/01/2010-31/12/2017. Patients with proctocolectomy or colectomy between 01/07/2010 and 31/12/2014 were identified, and surgery date was set as index. For patients with IPAA, the last surgery in the 6 months was taken as index. Non-surgery patients received random index. After propensity score matching, UC-related HCRU and cost were observed for three years post-index. RESULTS: Of 21,392 UC patients, 85 underwent surgery and 2655 did not. After matching, 76 were included in the surgery group and 114 in the non-surgery group. Matched cohorts did not differ in baseline characteristics and mortality rates where high in both groups (21.1% and 29.0%, respectively). The percentage of patients with at least one hospitalization in the follow-up period was higher in the surgery (53.9%) compared to the non-surgery group (25.4%, p<0.001). In contrast, the number of outpatient prescriptions of UC-related drugs in the non-surgery group (11.2) was almost twice as large as in the surgery group (5.8, p<0.001). Hospitalization cost was 4.6 times higher in the surgery (1955.5€) than in the non-surgery group (419.6€, p<0.001). Medication cost was three times higher in the non-surgery group (6519€) compared to the surgery group (2151.7€, p<0.001). CONCLUSIONS: Based on hospitalizations, outpatient visits, and medical treatment, results show a considerable patient burden in UC from surgery complications or disease exacerbation in case of colectomy.

Comparative effectiveness of second generation long-acting injectable antipsychotics based on nationwide database research in Hungary.

BACKGROUND: Schizophrenia is a severe condition that affects approximately 1% of the population. Certain elements of antipsychotic treatment can only be examined in large population, thus the need for population-based real-world analyses has been increasing. PATIENTS AND METHODS: Hungarian National Health Fund database includes all healthcare data of the population of Hungary. All patients diagnosed with schizophrenia between 01.01.2006 and 31.12.2015 were included in the study. We analyzed all patients with newly initiated second-generation antipsychotic during the inclusion period (01.01.2012-31.12.2013). Patients were followed for 2 years. All-cause treatment discontinuation served as the primary outcome of the study. Patients with newly initiated long-acting injectable treatments were further investigated in stratified analyses based on their previous treatment. RESULTS: 106,624 patients had schizophrenia diagnosis during the study period. 12,232 patients met the inclusion criteria for newly initiating second-generation antipsychotic during the inclusion period. The proportion of patients still on treatment after 1 year for oral treatments varied between 17% (oral risperidone) and 31% (oral olanzapine) while the analogous data for long acting injectables were between 32% (risperidone long acting) and 64% (paliperidone long acting one monthly). The 2-year data were similarly in favor of long-actings. Median time to discontinuation in the oral group varied between 57 days (clozapine) and 121 days (olanzapine). The median time to discontinuation for long-actings was significantly longer: between 176 and 287 days; in case of paliperidone long acting, median was not reached during the observation period. Patients receiving long-acting treatment switched from another long-acting remained on the newly initiated treatment significantly longer than those switched from orals. CONCLUSION: Our results indicate the superiority of second generation long-acting antipsychotics with regard to rates of treatment discontinuation and periods of persistence to the assigned medication.

Mortality and the relationship of somatic comorbidities to mortality in schizophrenia. A nationwide matched-cohort study.

AIM: We conducted a matched-cohort study to assess mortality in schizophrenia and the relationship of mortality with comorbid somatic conditions and suicide attempts. METHOD: A full-population register-based prospective matched-cohort study was performed including all eligible patients with schizophrenia in Hungary between 01/01/2005 and 31/12/2013. Control subjects were individually matched to patients with schizophrenia at a 5:1 ratio. The principal outcome measure was death due to any reason. A non-parametric approach was used for descriptive statistical purposes, the Kaplan-Meier model for survival analysis, and the Cox proportional-hazards regression model for inferential statistics. RESULTS: Patients with schizophrenia (n=65,169) had substantially higher risk of all-cause mortality than the control subjects (n=325,435) (RR=2.4; P<0.0001). Comorbidities and suicide attempts were associated with significantly increased mortality in both groups. As compared to the controls, 20-year old males with schizophrenia had a shorter life expectancy by 11.5years, and females by 13.7years; the analogous numbers for 45-year old schizophrenics were 8.1 and 9.6years, respectively. CONCLUSIONS: A significant mortality gap - mainly associated with somatic comorbidities - was detected between patients with schizophrenia and individually matched controls. Improved medical training to address the disparity in mortality, and many other factors including lack of resources, access to and model of medical care, lifestyle, medication side effects, smoking, stigma, need for early intervention and adequate health care organization could help to better address the physical health needs of patients with schizophrenia.

Mayfly and fish species identification and sex determination in bleak (Alburnus alburnus) by MALDI-TOF mass spectrometry.

Besides food quality control of fish or cephalopods, the novel mass spectrometry (MS) approaches could be effective and beneficial methods for the investigation of biodiversity in ecological research. Our aims were to verify the applicability of MALDI-TOF MS in the rapid identification of closely related species, and to further develop it for sex determination in phenotypically similar fish focusing on the low mass range. For MALDI-TOF MS spectra analysis, ClinProTools software was applied, but our observed classification was also confirmed by Self Organizing Map. For verifying the wide applicability of the method, brains from invertebrate and vertebrate species were used in order to detect the species related markers from two mayflies and eight fish as well as sex-related markers within bleak. Seven Ephemera larvae and sixty-one fish species related markers were observed and nineteen sex-related markers were identified in bleak. Similar patterns were observed between the individuals within one species. In contrast, there were markedly diverse patterns between the different species and sexes visualized by SOMs. Two different Ephemera species and male or female fish were identified with 100% accuracy. The various fish species were classified into 8 species with a high level of accuracy (96.2%). Based on MS data, dendrogram was generated from different fish species by using ClinProTools software. This MS-based dendrogram shows relatively high correspondence with the phylogenetic relationships of both the studied species and orders. In summary, MALDI-TOF MS provides a cheap, reliable, sensitive and fast identification tool for researchers in the case of closely related species using mass spectra acquired in a low mass range to define specific molecular profiles. Moreover, we presented evidence for the first time for determination of sex within one fish species by using this method. We conclude that it is a powerful tool that can revolutionize ecological and environmental research.

HPLC-MS/MS analysis of steroid hormones in environmental water samples.

Today, freshwaters, such as lakes and rivers, are subject to controlled pollution. Steroid hormones are chemically very stable highly lipophilic molecules. Their biological properties have a strong impact on the endocrine regulation of species. Steroids have estrogenic, androgenic, thyroidogenic or progestogenic effects and based on them, they could disturb the physiological mechanisms of freshwater species. We focused on progestins as they are the main active ingredients of contraceptive pharmaceuticals. Progestins have been shown to impair reproduction in fish, amphibians, and mollusks at low ng/L concentrations. Certain progestins, such as levonorgestrel (LNG) have androgenic properties also. We selected the most used active substances drospirenone (DRO), LNG, and progesterone (PRG) and then developed and optimized a liquid chromatographic-mass spectrometric method with solid-phase extraction to measure them. Using our sensitive method (LOQ 0.03-0.11 ng/L) we could measure steroids even between 0.1 and 1 ng/L. Analyzing freshwater samples from the Lake Balaton catchment area, we found influents where the concentration of these hormones was 0.26-4.30 (DRO), 0.85-3.40 (LNG), and 0.23-13.67 (PRG) ng/L. Out of 53 collecting places, 21 contained measurable progestin levels, which clearly demonstrates the applicability of our method, legitimates toxicology experiments with effected species, and indicates monitoring efforts.

Ectopic pregnancy prediction in women with a pregnancy of unknown location: data beyond 48 h are necessary.

STUDY QUESTION: Are there improvements in the accuracy of prediction of ectopic pregnancy (EP) in women with early symptomatic pregnancy using human chorionic gonadotrophin (hCG) curves when clinicians consider visits beyond the first 48 h after initial presentation? SUMMARY ANSWER: Two hCG values, measured 48 h (2 days) apart, are often not sufficient to accurately predict the outcome of a woman with a pregnancy of unknown location (PUL), but adding a third visit on Day 4 or 7 significantly improved the prediction for 1 in 15 women. WHAT IS KNOWN ALREADY: The use of serial hCG values is commonly used to aid in the prediction of the final diagnosis in women with a PUL. Initial outcome predictions based on two hCG values may often be incorrect. STUDY DESIGN, SIZE, DURATION: This retrospective multicenter cohort study included 646 women with a PUL, recruited over 2 years. Of these women, 146 were ultimately diagnosed with EP. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women presenting to the emergency room with first trimester pain or bleeding, with a PUL, at least 2 hCG values and a definitive final diagnosis from the University of Pennsylvania, University of Miami and University of Southern California, were recruited from 2007 to 2009. MAIN RESULTS AND THE ROLE OF CHANCE: Using currently recommended prediction rules, adding a third hCG evaluation on Day 4 after initial presentation significantly improved the accuracy of initial prediction from the first two values (48 h apart, or Day 2) by 9.3% (P = 0.015). Adding a third value on Day 7 improved prediction significantly by 6.7% (P = 0.031), compared with prediction based on first two values. The improvement in prediction by assessing four hCG values (Days 0, 2, 4 and 7) compared with three values (Days 0, 2 and 4) was 1.3% and not statistically significant. LIMITATIONS, REASONS FOR CAUTION: Missing data imputation likely biased results toward the null; predicted outcomes may not match those made by clinicians; and the study does not predict intrauterine pregnancy and spontaneous miscarriage separately. WIDER IMPLICATIONS OF THE FINDINGS: This study provides useful information for the prediction of outcomes for women with a symptomatic first trimester pregnancy of unknown location, but may not be generalizable to all pregnant women. STUDY FUNDING/COMPETING INTEREST(S): Supported by NIH grant numbers R01-HD036455 to Dr Barnhart and Dr Sammel, K24HD060687 to Dr Barnhart, and 5T32MH065218 to Ms. Zee. The authors have no conflicts of interest to declare.

The effect of octreotide on hepatic ischemia-reperfusion injury in a rabbit model.

BACKGROUND: Hepatic ischemic-reperfusion injury (HIRI) is a major cause of morbidity and mortality following liver surgery. Octreotide (Oct) has been reported to improve hepatocellular energy metabolism in a rat HIRI model. This study was designed to evaluate whether Oct could protect the liver of rabbits against ischemic-reperfusion (I/R) injury. METHODS: Twenty-four adult New Zealand rabbits were randomly divided into a sham operated group (Control), an ischemia/reperfusion group (I/R), and an ischemia/reperfusion + Oct pretreatment group (I/R + Oct). The hemodynamic (mean arterial pressure [MAP] and heart rate [HR]) changes, liver enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], and lactate dehydrogenase [LDH]) release, inflammatory cytokines (tumor necrosis factor [TNF]α and interleukin [IL]-1ß) levels, and endotoxin (ETX) levels were measured during I/R. RESULTS: Compared with the Control group, the MAP decreased and HR increased in I/R and I/R + Oct groups at ischemia 15 minutes (P < .05) but were less in the I/R + Oct group relative to the I/R group (P < .05). ALT, AST, LDH, IL-1ß, and ETX levels were increased in the I/R and I/R + Oct groups at ischemia 30 minutes (P < .05), however, the increase was lower in the I/R + Oct group relative to the I/R group (P < .05). Bcl-2 expression in the I/R + Oct group was higher compared with other groups (P < .05) and Bax expression in the I/R group was reduced compared with other groups (P < .05). Hepatocellular damage in the I/R + Oct group appeared to be less than in the I/R group by microscopy. CONCLUSIONS: Oct pretreatment attenuated hemodynamic changes and decreased liver enzyme changes induced by HIRI in a rabbit model. The protection mechanisms of Oct may be related to reduced ETX levels, down-regulation of the inflammatory cytokines TNFα and IL-1ß, and inhibition of hepatocellular apoptosis, as well as the modulation of the mitochondrion-mediated Bcl-2/Bax apoptosis pathway. Based on our study it appears that Oct may be useful in decreasing liver injury after liver surgery and/or transplantation and may serve as a promising agent against HIRI.

Complications of three sacrospinous ligament fixation techniques.

OBJECTIVES: To compare the complications of three techniques used to pass the suture through the sacrospinous ligament when performing sacrospinous ligament fixation (SSLF): (1) the standard needle driver with direct visualization; (2) the Deschamps ligature carrier by palpation; and (3) the Miya hook ligature carrier by palpation. MATERIALS AND METHODS: A retrospective chart review of 240 patients undergoing SSLF was performed. A standard needle driver with direct visualization was used for 46 patients; the Deschamps ligature carrier was used for 173, and the Miya hook for 21 patients. Intraoperative and postoperative complications were compared between the groups. RESULTS: Twelve women (5%) had intraoperative and forty women (17%) had postoperative complications suspected directly from the suture placement. There was no statistically significant difference in the rate of total intraoperative complications among the three groups. The proportion of patients with postoperative complications that were felt to be directly related to the suture passage technique was significantly higher in the Deschamps group compared to the direct visualization group (18% vs 2%, P=0.002). CONCLUSION: Passing the suture through the sacrospinous ligament under direct visualization may result in less intra and postoperative complications.

Increased circulating lipid peroxides in severe preeclampsia activate NF-kappaB and upregulate ICAM-1 in vascular endothelial cells.

Preeclampsia is a systemic disease of pregnancy characterized by maternal hypertension, proteinuria, and edema. These clinical pathological findings may be attributed to abnormalities in vascular endothelial activation secondary to increased oxidative stress. To test the hypothesis that increased circulating lipid peroxides in preeclamptic women activate vascular endothelial cells, we determined NF-kappaB transcriptional activity and ICAM-1 expression in human umbilical vein endothelial cells (HUVEC) cultured with plasma from women with severe preeclampsia (preeclamptic plasma, N = 12) or plasma from normal pregnancies (normal plasma, N = 12). Preeclamptic women had increased circulating lipid peroxides compared with normal pregnant women, as demonstrated by a 4.5-fold higher concentration of plasma malondialdehyde (PkB luciferase reporter construct transfected into HUVEC, preeclamptic plasma was found to up-regulate HUVEC NF-kappaB activity by 2.5-fold when compared with normal plasma (PkB activation in response to preeclamptic-plasma by 77% (PkB activation and ICAM-1 expression on HUVEC, which can be inhibited by vitamin E and N-acetyl-cysteine.

Improvements in the accuracy and the repeatability of long trace profiler measurements.

Modifications of the long trace profiler at the Advanced Photon Source at Argonne National Laboratory have significantly improved its accuracy and repeatability for measuring the figure of large flat and long-radius mirrors. Use of a Dove prism in the reference beam path corrects phasing problems between mechanical errors and thermally induced system errors. A single reference correction now completely removes both of these error signals from the measured surface profile. The addition of a precision air conditioner keeps the temperature in the metrology enclosure constant to within +/-0.1 degrees C over a 24-h period and has significantly improved the stability and the repeatability of the measurements. Long-radius surface curvatures can now be measured absolutely with a high degree of confidence. These improved capabilities are illustrated with a series of measurements of a 500-mm-long mirror with a 5-km radius of curvature. The standard deviation in the average of ten slope profile scans is 0.3 microrad, and the corresponding standard deviation in the height error is 4.6 nm.

The expression of interleukin-1 alpha, interleukin-1 beta, and interleukin-1 receptor type I mRNA during preimplantation mouse development.

Interleukin-1 (IL-1) plays an important role in implantation of the early embryo since blockade of the IL-1 receptor prevents implantation in the mouse. Whether IL-1 blockade during implantation has a direct effect on the embryo or only the uterus is unknown since reliable data are not available concerning the expression of IL-1 or IL-1 receptor on the preimplantation embryo. Because of the significant role for IL-1 in implantation, we investigated the potential for an embryonic-maternal IL-1 signaling mechanism during mouse preimplantation embryo development. Reverse transcriptase-polymerase chain reaction (RT-PCR) was performed for IL-1 alpha, IL-1 beta and IL-1 receptor type I (IL-1R) on mRNA isolated from mouse preimplantation embryos and uteri collected between the 2-cell to blastocyst stage. Preimplantation embryos have the capability to produce IL-1 beta after the 4-cell stage of development since IL-1 beta mRNA was detected from the 4-cell to blastocyst stage but not at the 2-cell stage. Unlike IL-1 beta, IL-1 alpha was not expressed in preimplantation embryos. It is unlikely that IL-1 has a direct effect on the preimplantation embryo since IL-1R mRNA was not expressed in preimplantation embryos. In contrast, IL-1 could have a direct effect on the uterus since IL-1R mRNA was found to be expressed in uteri at all developmental time points. Our findings suggest that there is a potential embryonic-maternal IL-1 signaling mechanism through the expression of IL-1 beta by the preimplantation embryo and the expression of IL-1R in the uterus.

Decreased birefringence of the superficial zone collagen network in the canine knee (stifle) articular cartilage after long distance running training, detected by quantitative polarised light microscopy.

OBJECTIVE: To investigate the effects of a one year programme of running training (up to 40 km/day for 15 weeks) on the spatial orientation pattern of collagen and glycosaminoglycans in articular cartilage in different parts of the knee (stifle) and shoulder joints of young beagle dogs. METHODS: Area specific measurements of the optical path difference (= retardation, gamma) and the cartilage zone thickness were performed using conventional procedures and a new computer based quantitative polarised light microscopy method. Transmission electron microscopy was used to determine the zonal volume density of collagen fibrils. The concentrations of collagen and hydroxypyridinium crosslinks were investigated biochemically. RESULTS: Running training decreased gamma by 24-34% (p < 0.05) in the superficial zone of the lateral femoral condyle articular cartilage and at the centre of the tibial condyles. Gamma of glycosaminoglycans decreased by 26% (p < 0.05) in the superficial zone of the lateral condyle of the femur, but at the same site the volume density of collagen fibrils was unchanged. Neither the collagen concentration nor the concentration of hydroxypyridinium crosslinks was altered as a result of running. In both control and runner dogs, the thickness and gamma values of the superficial zone were greater in the humerus and the femur than in the tibia. CONCLUSION: Endurance type running exercise in beagles caused a reduction in the superficial zone birefringence of the articular cartilage, which indicates either a disorganisation or a reorientation of the superficial zone collagen network. Articular cartilage showed marked variability of collagen network organisation over the different knee (stifle) joint articular surfaces.

The expression of stem cell factor and its receptor, c-kit in human endometrium and placental tissues during pregnancy.

Stem cell factor (SCF) and its receptor Kit regulate the proliferation and survival of early hematopoietic cell types as well as germ cells and melanocytes. As SCF augments the effects of several hematopoietic growth factors that are produced in reproductive tissues during pregnancy and also plays an important role in cell migration, proliferation, and survival, we studied the expression and localization of this receptor/ligand in human endometrial and placental tissues. Kit was detected by Western blot analysis in early decidual and placental tissues (8-19 weeks gestation) and in term placenta. Immunohistochemistry localized Kit mainly in trophoblast and to a lesser extent in scattered cells in the placental villous core and decidual stroma. Ribonuclease protection assay showed that SCF messenger ribonucleic acid (mRNA) expression increased 3-fold in decidua from early pregnancy compared to proliferative and secretory endometrium (P < 0.05). Placental tissues expressed 4- to 8-fold higher levels of SCF mRNA compared to decidus (P < 0.05). Isolated placental villous core expressed 7-fold higher levels of SCF mRNA than did trophoblast (P < 0.05). Thus, SCF and its receptor Kit are expressed in human endometrium and placental tissues during pregnancy, and the pattern of receptor/ligand expression suggests that endometrial and placental villous core SCF may have a paracrine effect on trophoblast through the receptor Kit.