Combination of Proactive Molecular Risk Classifier for Endometrial cancer (ProMisE) with sonographic and demographic characteristics in preoperative prediction of recurrence or progression of endometrial cancer.

OBJECTIVE: To evaluate the ability of demographic and sonographic variables and the Proactive Molecular Risk Classifier for Endometrial cancer (ProMisE) classification to predict preoperatively tumor recurrence or progression in women with endometrial cancer. METHODS: The study included 339 women with histologically confirmed endometrial cancer who underwent expert transvaginal ultrasound in a single center before surgery as part of the prospective International Endometrial Tumor Analysis 4 study or who were evaluated using the same protocol. The tumors were classified according to histotype, FIGO (International Federation of Gynecology and Obstetrics) grade and FIGO stage. In addition, molecular analysis was performed for classification into the four ProMisE subtypes: polymerase-ϵ exonuclease domain mutations (POLE EDM), mismatch repair proteins deficiency (MMR-D), protein 53 wild type (p53 wt) and protein 53 abnormal (p53 abn). Demographic and preoperative sonographic characteristics, tumor recurrence or progression and survival were compared between the ProMisE subgroups. Cox regression analysis was used to identify prognostic factors associated with recurrence or progression, using univariable models to study crude associations and multivariable models to study adjusted associations. Logistic regression and receiver-operating-characteristics (ROC)-curve analysis were used to assess the predictive ability of the preoperative prognostic factors regarding recurrence or progression of cancer within 3 years after surgery, and to compare their predictive ability to that of the European Society for Medical Oncology (ESMO) preoperative (based on depth of myometrial invasion, histotype and grade) and postoperative (based on histotype, grade, surgical stage and lymphovascular space invasion) risk classifications. In a separate subanalysis, cases were stratified according to ProMisE p53 abn status (present vs absent) and sonographic tumor size (anteroposterior (AP) diameter < 2 cm vs ≥ 2 cm). RESULTS: Median follow-up time from surgery was 58 months (interquartile range, 48-71 months; range, 0-102 months). Recurrence or progression of cancer occurred in 51/339 (15%) women, comprising 14% of those with MMR-D, 8% of those with POLE EDM, 9% of those with p53 wt and 45% of those with p53 abn ProMisE subtype. On multivariable analysis, age, waist circumference, ProMisE subtype and tumor extension and AP diameter on ultrasound were associated with tumor recurrence or progression. A multivariable model comprising ProMisE subtype, age, waist circumference and sonographic tumor extension and size (area under the ROC curve (AUC), 0.89 (95% CI, 0.85-0.93)) had comparable ability to predict tumor recurrence/progression to that of a multivariable model comprising histotype, grade, age, waist circumference and sonographic tumor extension and size (AUC, 0.88 (95% CI, 0.83-0.92)), and better predictive ability than both the preoperative (AUC, 0.74 (95% CI, 0.67-0.82); P < 0.01) and postoperative (AUC, 0.79 (95% CI, 0.72-0.86); P < 0.01) ESMO risk classifications. Women with a combination of non-p53 abn subtype and tumor size < 2 cm (164/339 (48%)) had a very low risk (1.8%) of tumor recurrence or progression. CONCLUSIONS: The combination of demographic characteristics, sonographic findings and ProMisE subtype had better preoperative predictive ability for tumor recurrence or progression than did the ESMO classification, supporting their use in the preoperative risk stratification of women with endometrial cancer. The combination of p53 status with ultrasound tumor size has the potential to identify preoperatively a large group of women with a very low risk of recurrence or progression. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. - Legal Statement: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Is out-of-hours cholecystectomy for acute cholecystitis associated with complications?

BACKGROUND: Existing data on the safety of out-of-hours cholecystectomy are conflicting. The aim of this study was to investigate whether out-of-hours cholecystectomy for acute cholecystitis is associated with a higher risk for complications compared with surgery during office hours. METHODS: This was a population-based cohort study. The Swedish Gallstone Surgery and Endoscopic Retrograde Cholangiopancreatography Register (GallRiks) was used to investigate the association between out-of-hours cholecystectomy for acute cholecystitis and complications developing within 30 days. Data from patients who underwent cholecystectomy between 2006 and 2017 were collected. Out-of-hours surgery was defined as surgery commencing between 19.00 and 07.00 hours on weekdays, or any time at weekends (Friday 19.00 hours to Monday 07.00 hours). Multivariable logistic regression analysis was used to assess the risk of complications, with time of procedure as independent variable. The proportion of open procedures and proportion of procedures exceeding 120 min were also analysed. Adjustments were made for sex, age, ASA grade, time between admission and surgery, and hospital-specific features. RESULTS: Of 11 153 procedures included, complications occurred within 30 days in 1573 patients (14·1 per cent). The adjusted odds ratio (OR) for complications for out-of-hours versus office-hours surgery was 1·12 (95 per cent c.i. 0·99 to 1·28). The adjusted OR for procedures completed as open surgery was 1·39 (1·25 to 1·54), and that for operating time exceeding 120 min was 0·63 (0·58 to 0·69). CONCLUSION: Out-of-hours complications may relate to patient factors and the higher proportion of open procedures.

ANTECEDENTES: Los datos existentes sobre la seguridad de la colecistectomía fuera del horario laboral son discordantes. El objetivo de este estudio fue investigar si la colecistectomía para el tratamiento de la colecistitis aguda realizada fuera del horario laboral se asocia con un mayor riesgo de complicaciones en comparación con la cirugía efectuada durante el horario laboral. MÉTODOS: Se trata de un estudio de cohortes de base poblacional. Se utilizó el registro Swedish Gallstone Surgery and Endoscopic Retrograde Cholangiopancreatography Register (GallRiks) para examinar la asociación entre la colecistectomía por colecistitis aguda realizada fuera del horario laboral y las complicaciones a los 30 días. Se recogieron los datos de los pacientes en los que se realizó una colecistectomía entre 2006 y 2017. Se definió como cirugía fuera del horario laboral aquella realizada entre las 19:00 y las 07:00 de lunes a viernes y en cualquier momento durante los fines de semana (de viernes 19:00 a lunes 07:00) Se realizó un análisis de regresión logística multivariable para evaluar el riesgo de complicaciones, considerando la hora de la cirugía como variable independiente. También se analizó el porcentaje de intervenciones por vía abierta y el de aquellas cuya duración excedió de los 120 minutos. Se realizaron ajustes por sexo, edad, puntuación ASA, días desde el ingreso hasta la cirugía y características específicas del hospital. RESULTADOS: Se produjeron 1.573 (14,1%) complicaciones en las 11.153 intervenciones incluidas. La razón de oportunidades, odds ratio (OR) ajustada para las complicaciones comparando la cirugía fuera del horario laboral con la cirugía dentro del horario laboral, fue de 1,12 (i.c. del 95% 0,99-1,28). La OR ajustada para los procedimientos realizado por vía abierta fue de 1,39 (1,25-1,54). La OR ajustada para el tiempo operatorio > 120 minutos fue de 0,63 (0,58-0,69). CONCLUSIÓN: Las complicaciones que suceden en la cirugía efectuada fuera del horario laboral es más probable que se deban a factores relacionados con el paciente que con la hora del día en que se practica la cirugía. Debe tenerse en cuenta que las intervenciones realizadas por vía abierta fuera del horario laboral tienen una mayor morbilidad.

Muscle endurance, strength, and active range of motion in patients with different subphenotypes in systemic sclerosis: a cross-sectional cohort study.

OBJECTIVE: Proximal muscle weakness is common in patients with systemic sclerosis (SSc). Dynamic muscle endurance, muscle strength in the lower extremities, and active range of motion (AROM) in the upper extremities are less studied. We investigated functional muscle endurance, strength, and AROM, and explored differences depending on skin and/or lung involvement in SSc patients. METHOD: The study divided 205 patients with limited/diffuse cutaneous systemic sclerosis (lcSSc/dcSSc) into no-mild and moderate-end-stage lung involvement, the latter based on the Medsger disease severity score. Dynamic muscle endurance in shoulder and hip flexion was assessed by the Functional Index-2, lower extremity muscle strength by the Timed-Stands Test (TST), and shoulder-arm AROM by the Functional Shoulder Assessment (FSA). RESULTS: Shoulder and hip flexion muscle endurance were reduced in relation to reference values median (IQR) [53% (27-100%) and 40% (23-90%), respectively, p < 0.001]. Patients with moderate-end-stage lung involvement had less endurance in shoulder [39% (21-71%) and hip flexion 35% (20-70%)] than patients with no-mild lung involvement [57% (33-99%) and 48% (28-100%), p < 0.05]. All patients, regardless of subtype/grouping, needed longer to complete the TST [21 s (17-27 s)] compared to reference values [17 s (15-18 s), p < 0.001], and patients with moderate-end-stage lung involvement had worse TST score than patients with no-mild lung involvement,  [25 s (18-30 s) vs 19 s (16-25 s), p < 0.001]. The FSA sum scores were lower compared with reference values (p < 0.01). DcSSc patients had a lower FSA-sum score [53 (48-57)] than lcSSc patients [57 (52-60), p < 0.01]. CONCLUSION: SSc patients have markedly reduced muscle endurance in the upper and lower extremities, reduced muscle strength in the lower extremities, and impaired AROM in the shoulders and arms. Patients with moderate-end-stage lung involvement had more impaired muscle endurance and strength but no differences were found between lcSSc and dcSSc patients. Not only muscle strength, but also dynamic muscle endurance should be measured in SSc patients.

Slow-release vaginal insert of misoprostol versus orally administrated solution of misoprostol for the induction of labour in primiparous term pregnant women: a randomised controlled trial.

OBJECTIVE: To compare the World Health Organization (WHO) recommended orally administrated dosage of misoprostol (25 µg) with a vaginal slow-release (7 µg/hour) insert of misoprostol regarding time from induction to delivery and safety of the method. DESIGN: Open label, Randomised controlled trial (RCT). SETTING: Delivery ward at a secondary referral hospital in Stockholm, Sweden, from 1 October 2016 to 21 February 2018. POPULATION: One hundred and ninety-six primiparous women with singletons in cephalic presentation at ≥37 weeks of gestation and with a Bishop score of ≤4. METHODS: Women were randomised to an oral solution of misoprostol (Cytotec® n = 99) or vaginal slow-release misoprostol (Misodel® [MVI] n = 97). MAIN OUTCOME MEASURES: Primary outcome: time from induction to vaginal delivery. SECONDARY OUTCOMES: mode of delivery; proportion of vaginal deliveries within 24 hours (VD24); neonates with an Apgar score of <7 at 5 minutes; pH < 7.10; postpartum haemorrhage (PPH) of >1000 ml; hyperstimulation; and women's delivery experience (VAS). RESULTS: There was no difference in the time to delivery [corrected] (median 21.1 hours in the MVI group and 23.2 hours in the oral group; Kaplan-Mayer log rank P = 0.31). There was no difference regarding the proportion of VD24 (50.5 versus 55.7%, P = 0.16). Hyperstimulation with non-reassuring cardiotocography (CTG) was more common in the MVI group (14.4 versus 3.0%, P < 0.01). Terbutaline (Bricanyl® ) was used more often for hyperstimulation in the MVI group (22.7 versus 4.0%, P < 0.01). There was no difference in the numbers of children admitted to the neonatal intensive care unit (NICU). CONCLUSIONS: Vaginal delivery after induction of labour (IOL) with slow-release misoprostol did not result in a shorter time from induction to vaginal delivery, compared with oral misoprostol solution, but was associated with a higher risk for hyperstimulation and fetal distress. There were no differences in mode of delivery or neonatal outcome. TWEETABLE ABSTRACT: IOL with MVI was similar to oral solution of misoprostol but hyperstimulation and fetal distress were more common.

Can sensation of cold hands predict Raynaud's phenomenon or paraesthesia?

Background: Raynaud's phenomenon and neurosensory symptoms are common after hand-arm vibration exposure. Knowledge of early signs of vibration injuries is needed. Aims: To investigate the risk of developing Raynaud's phenomenon and paraesthesia in relation to sensation of cold hands in a cohort of male employees at an engineering plant. Methods: We followed a cohort of male manual and office workers at an engineering plant in Sweden for 21 years. At baseline (1987 and 1992) and each follow-up (1992, 1997, 2002, 2008), we assessed sensation of cold, Raynaud's phenomenon and paraesthesia in the hands using questionnaires and measured vibration exposure. We calculated risk estimates with univariate and multiple logistic regression analyses and adjusted for vibration exposure and tobacco usage. Results: There were 241 study participants. During the study period, 21 individuals developed Raynaud's phenomenon and 43 developed paraesthesia. When adjusting the risk of developing Raynaud's phenomenon for vibration exposure and tobacco use, the odds ratios were between 6.0 and 6.3 (95% CI 2.2-17.0). We observed no increased risk for paraesthesia in relation to a sensation of cold hands. Conclusions: A sensation of cold hands was a risk factor for Raynaud's phenomenon. At the individual level, reporting a sensation of cold hands did not appear to be useful information to predict future development of Raynaud's phenomenon given a weak to moderate predictive value. For paraesthesia, the sensation of cold was not a risk factor and there was no predictive value at the individual level.

Self-reported physical capacity and activity in patients with systemic sclerosis and matched controls.

OBJECTIVE: The aim was to investigate differences in self-reported physical capacity and activity between systemic sclerosis (SSc) patients and population-based controls, as well as between patients with normal-mild, or moderate-severe, lung disease and their respective controls. METHOD: The study included 106 patients fulfilling the American College of Rheumatology SSc criteria and 106 controls, individually matched for age and gender. Patients were subdivided into normal-mild and moderate-severe lung disease based on results from pulmonary function tests and SSc severity scale. Participants answered questions regarding physical capacity and activity, exercise, and time spent sitting. RESULTS: SSc patients reported overall lower capacity for walking, jogging, and running (p < 0.001), and more limiting factors for physical capacity than controls (p < 0.001). Both patients with normal-mild and moderate-severe lung disease also reported lower overall physical capacity than their respective controls (p = 0.001, p < 0.001). Normal-mild lung disease patients reported pain more often than their controls (p < 0.05), whereas moderate-severe lung disease patients reported cardiopulmonary disease (p < 0.001) and reduced muscle strength (p = 0.03) as limiting factors for physical capacity more often than their controls. More patients than controls had 'never exercised' for at least 30 min per occasion within the past year (28% vs 15%, p = 0.03); however, there were no differences overall between patients and controls in frequency of exercise, physical activity, or time spent sitting. CONCLUSION: Although SSc patients reported lower physical capacity and more limiting factors for physical capacity than controls, there were no differences in reported physical activity and time spent sitting. Further development of physical activity programmes for SSc patients, especially for patients who never exercise or have physical impairments, is needed.

COMT genotype and non-recovery after a whiplash injury in a Northern European population.

BACKGROUND: The COMT (Catechol-O-Methyl Transferase) gene may influence a person's vulnerability to develop long-term pain and some COMT single nucleotide polymorphisms (SNPs) may associate with patterns of acute or chronic pain. Many patients with whiplash-associated disorders (WADs) suffer from long-term pain and other related symptoms, but it is less known if genetic factors play a role in the recovery process. The primary aim of this study was to evaluate whether self-reported non-recovery, including pain, was related to COMT genotype in patients with WAD. The secondary aim was to investigate whether or not background factors, including mental health, were related to genotype and non-recovery. METHODS: A total of 133 patients with neck pain after a whiplash trauma were included. Background factors were collected and blood samples were taken during the acute phase after the accident. DNA was isolated from blood and used to genotype the SNPs rs6269, rs4633, rs4818 and rs4680 in the COMT gene; additionally haplotypes were estimated and haplogenotypes inferred. The patients were followed up after 12 months and asked to rate their recovery including pain, mental health and quality of life. RESULTS: The overall reported non-recovery rate at 12 months was 44% with no significant differences in distribution of the COMT haplotypes. High levels of self-reported pain (OR 7.2) and anxiety (OR 4.4) after the accident were associated with non-recovery, but not related to the haplotypes. None of the other background factors were related to the haplotypes or non-recovery. CONCLUSION: No association between self-reported non-recovery or pain levels and COMT haplotypes in patients with acute whiplash injuries could be detected. Independent replications are necessary to discard the hypothesis that COMT haplotypes do not influence non-recovery or pain levels in patients with acute whiplash injuries. High levels of initial pain and anxiety were associated with non-recovery, thereby confirming previously published reports.

Incidence of groin hernia repairs in women and parity: a population-based cohort study among women born in Sweden between 1956 and 1983.

INTRODUCTION: The aim of this study was to evaluate the association between parity and the incidence rate of groin hernia repair in women. METHOD: This study was based on two Swedish national registers, the Medical Birth Register (MBR), and the Swedish Hernia Register (SHR). The cohort constituted of women born between 1956 and 1983. Data on vaginal and cesarean deliveries were retrieved from the MBR. The birth and hernia registers were cross matched to identify hernia repairs carried out after deliveries. RESULTS: A total of 1,535,379 women were born between 1956 and 1983. Among these, 1,417,237 (92.3%) were registered for at least one birth. The incidence rate for Inguinal Hernia Repair (IHR) and Femoral Hernia Repair (FHR) was 10.7 per 100,000 person-year and 2.6 per 100,000 person-year, respectively. Compared with women registered for one delivery, the incidence rate ratio for IHR was 1.31 (95% Confidence Interval: 1.23-1.40) among women registered for two deliveries, 1.70 (1.58-1.82) among women registered for ≥ 3 deliveries. Additionally, the incidence rate ratios were higher 1.30 (1.14-1.49) and 1.70 (1.49-1.95) for FHR among women with two and ≥ 3 registered deliveries, respectively. CONCLUSION: In the present cohort, higher parity was associated with a higher incidence of inguinal as well as FHRs.

Appendectomy during pregnancy: rates, safety, and outcomes over a five-year period. A hospital-based follow-up study.

INTRODUCTION: Appendicitis is the most common acute abdominal complication during pregnancy. If appendix perforation occurs there is an increasing risk of preterm delivery and other pregnancy complications. OBJECTIVE: To assess the outcome of pregnancy after appendectomy, the mode of surgery used, appendectomy rates, and complications. METHODS: A prospective cohort study of pregnant women with, or without, appendectomy at South Stockholm General Hospital, December 2015 to February 2021 in a setting where pregnant women are prioritized for surgery and laparoscopic surgery was standard of care in first half of pregnancy. Data on preoperative imaging, surgical method, intraoperative findings, microscopic findings, hospital stay, pregnancy, and 30-day complications were prospectively recorded in a local appendectomy register. A non-pregnant control group was gathered comprising women of fertile age in the same study interval. RESULTS: During the study period 50 pregnant women, of whom 44 gave birth, underwent appendectomy of 38 199 women giving birth. There were no differences between women with or without appendectomy in proportion of preterm delivery (4.5% vs. 5.6%), small-for-gestational age (2.3% vs. 6.2%), or Cesarean delivery (18.2% vs. 20.4%). The rate of appendix perforation was 19% in non-pregnant control group compared to 12% among pregnancy. There was no case of perforated appendix in the second half of pregnancy. However, women with gestational age > 20 weeks more frequently had an unaffected appendix compared to those operated ≤ 20 gestational weeks (4/11 vs. 2/39, p = .005). Laparoscopic surgery was used in 97% of non-pregnant control group, 92% of appendectomies ≤ 20 weeks gestation, and in 27% >20 weeks. As compared to first half, the appendectomy rate was three times lower during the second half of pregnancy. Pregnant women had priority for surgery < 6 h compared to < 24 h among non-pregnant women, this resulted in a shorter time-to-surgery among pregnant women (p < .001). CONCLUSION: Routine laparoscopic surgery and time priority for pregnant surgery is associated with a low risk of perforation, preterm birth and other complications. However, a low threshold for surgery may increase the risk of a negative exploration.

Associations between advanced maternal age and psychological distress in primiparous women, from early pregnancy to 18 months postpartum.

OBJECTIVE: To investigate if advanced maternal age at first birth increases the risk of psychological distress during pregnancy at 17 and 30 weeks of gestation and at 6 and 18 months after birth. DESIGN: National cohort study. SETTING: Norway. SAMPLE: A total of 19 291 nulliparous women recruited between 1999 and 2008 from hospitals and maternity units. METHODS: Questionnaire data were obtained from the longitudinal Norwegian Mother and Child Cohort Study, and register data from the national Medical Birth Register. Advanced maternal age was defined as ≥ 32 years and a reference group of women aged 25-31 years was used for comparisons. The distribution of psychological distress from 20 to ≥ 40 years was investigated, and the prevalence of psychological distress at the four time-points was estimated. Logistic regression analyses based on generalised estimation equations were used to investigate associations between advanced maternal age and psychological distress. MAIN OUTCOME MEASURES: Psychological distress measured by SCL-5. RESULTS: Women of advanced age had slightly higher scores of psychological distress over the period than the reference group, also after controlling for obstetric and infant variables. The youngest women had the highest scores. A history of depression increased the risk of distress in all women. With no history of depression, women of advanced age were not at higher risk. Changes over time were similar between groups and lowest at 6 months. CONCLUSION: Women of 32 years and beyond had slightly increased risk of psychological distress during pregnancy and the first 18 months of motherhood compared with women aged 25-31 years.

High levels of 15-oxygenated steroids in circulation of patients with multiple sclerosis: fact or fiction?

15-Oxygenated cholesterol species such as 5α-cholest-8(14)ene-3ß,15α-diol (15HC) and 3ß-hydroxy-5α-cholest-8(14)-en-15-one (15KC) are commercially available synthetic products unlikely to occur in biological systems. Surprisingly, Farez et al. recently reported that these two steroids occur in human circulation at levels considerably higher than those of any other endogenous oxysterol [Farez, M. et al. 2009. Toll-like receptor 2 and poly(ADP-ribose) polymerase 1 promote central nervous system neuroinflammation in progressive EAE. Nat. Immunol. 10: 958-964]. The levels were reported to be increased in patients with multiple sclerosis in a progressive phase and the authors suggested that this could be utilized diagnostically. Based on extensive in vitro experiments exposing cells to the same high levels of 15HC as found in vivo (1000 ng/ml) the authors concluded that 15HC may be an important pathogenetic factor in multiple sclerosis. Using combined gas chromatography-mass spectrometry we fail to detect significant plasma levels of 15HC either in healthy controls or in patients with multiple sclerosis (levels < 2 ng/ml). If 15KC is present in these plasma samples, the concentration of it must be <10 ng/ml. Our failure to detect significant levels of the above steroids could not be due to loss during hydrolysis and work-up because recovery of the added two oxysterols was close to 100%. Autoxidation of lipoprotein-bound cholesterol resulted in extensive conversion of cholesterol into 7-oxygenated but not 15-oxygenated sterols. We conclude that if present there are trace amounts only of the above 15-oxygenated steroids in human circulation and that the role of such oxysterols as pathogenetic factors and biomarkers must be reconsidered.

Enhanced production of 24S-hydroxycholesterol is not sufficient to drive liver X receptor target genes in vivo.

BACKGROUND: Oxysterols such as 24S-hydroxycholesterol (OHC) and 27-OHC are intermediates of cholesterol excretion pathways. In addition, they are putative endogenous agonists of the liver X receptor (LXR) class of nuclear hormone receptors and are thought to be important mediators of cholesterol-dependent gene regulation. 24S-OHC is one of the most efficient endogenous LXR agonists known and is present in the brain and in the circulation at relatively high levels. OBJECTIVES: To explore the regulatory importance of 24S-OHC in vivo. DESIGN: We developed a transgenic mouse model in which human cholesterol 24-hydroxylase, the enzyme responsible for the formation of 24S-OHC, was expressed under the control of a promoter derived from the ß-actin gene. RESULTS: Both male and female transgenic mice had elevated levels of cerebral, plasma, biliary and faecal 24S-OHC. According to the faecal excretion results, production of 24S-OHC was increased four- to sevenfold. Gene expression profiling revealed that the elevated production of 24S-OHC did not result in the anticipated activation of LXR target genes in the brain or liver. CONCLUSION: In spite of the fact that 24S-OHC is a highly effective agonist of LXRs in vitro, it is not a critical activator of target genes to this nuclear receptor in vivo, either in the brain or in the liver.

The burden of hepatitis C in Sweden: a national study of inpatient care.

The spread of hepatitis C virus (HCV) in Sweden in the 1970s indicated that serious liver complications (SLC) would increase in the 2000s. The aim of this study was to analyse the burden of HCV-associated inpatient care in Sweden, to demonstrate the changes over time and to compare the findings with a noninfected population. The HCV-cohort (n: 43,000) was identified from the national surveillance database 1990-2006, and then linked to national registers to produce an age-, sex-, and region-matched noninfected comparison population (n: 215,000) and to obtain information on demographics, cancers, inpatient care and prescriptions. Cox regression was used to estimate the likelihood (hazard ratios) for admission to hospital in the HCV compared with the noninfected cohort. The hazard ratios were 4.03 (95% CI: 3.98-4.08) for all care, 77.52 (71.02-84.60) for liver-related care and 40.74 (30.58-54.27) for liver cancer care. The admission rate in the HCV-cohort compared with the noninfected cohort, the rate ratio (age- and sex-adjusted) for all inpatient care was 5.91 (95% CI: 5.87-5.94), and the rate ratio for liver-related care was 70.05 (66.06-74.28). In the HCV-cohort, 45% of all episodes were for psychiatric, mostly drug-related, care. Inpatient care for SLC increased in the 2000s. To conclude, drug-related care was common in the HCV-infected cohort, the demand for liver-related care was very high, and SLC increased notably in the 2000s, indicating that the burden of inpatient care from serious liver disease in HCV-infected individuals in Sweden is an increasing problem.

Electron backscattering diffraction and X-ray diffraction studies of interface relationships in Sr3Ru2O7/Sr2RuO4 eutectic crystals.

Sr3Ru2O7/Sr2RuO4 eutectic system is investigated by electron backscattering diffraction (EBSD) and X-ray diffraction (XRD). The eutectic growth enables the solidification of the two phases in an ordered lamellar pattern extending along the growth direction, namely the b-axis direction. The eutectic material thus provides in the a-c plane two distinct interfaces having different microstructures with respect to the growth direction. Our analysis shows that, across the inplane c-axis direction (characterized by a poor lattice matching), the b-axis orientation is not constant at the individual interfaces, showing an orientation spread of about 5°. However, across the in-plane a-axis direction (characterized by a good lattice matching), the b-axis orientation does not change within a few tenths of degree (about 0.25°). Such information at nanoscale is also verified on a macroscopic level by standard XRD investigation.

Soft nanostructuring of YBCO Josephson junctions by phase separation.

We have developed a new method to fabricate biepitaxial YBa2 Cu3 O7-δ (YBCO) Josephson junctions at the nanoscale, allowing junctions widths down to 100 nm and simultaneously avoiding the typical damage in grain boundary interfaces due to conventional patterning procedures. By using the competition between the superconducting YBCO and the insulating Y2 BaCuO5 phases during film growth, we formed nanometer sized grain boundary junctions in the insulating Y2 BaCuO5 matrix as confirmed by high-resolution transmission electron microscopy. Electrical transport measurements give clear indications that we are close to probing the intrinsic properties of the grain boundaries.

Clinicopathologic factors associated with malignant transformation of oral leukoplakias: a retrospective cohort study.

It is clinically challenging to identify oral leukoplakias that have a high risk of undergoing malignant transformation. The aim of this retrospective study was to elucidate the associations between malignant transformation of oral leukoplakias and various clinicopathologic factors. Patients with a diagnosis of clinical oral leukoplakia, verified through histopathologic examination and with access to digital images of the lesion, were retrospectively included for the period 2003-2013. Using the clinical images, all lesions were re-evaluated regarding diagnosis and clinical subtype. Of the 234 included patients, with a median follow-up of 9 years, 27 (11.5%) developed oral squamous cell carcinoma. Among the clinicopathologic factors investigated, non-homogeneous oral leukoplakia (OL), OL with dysplasia, and OL localized to the tongue showed statistically significant increased rates of malignant transformation in the multivariate Cox regression analysis. Non-homogeneous OL showed a 15.2-times higher transformation rate than homogenous OL (P<0.001). Dysplastic leukoplakias developed into carcinomas 2.4-times more often than did non-dysplastic leukoplakias (P=0.048). OL located on the tongue showed a 2.8-times higher malignant transformation rate than OLs at other oral locations (P=0.018), when other locations were combined into one group. Non-homogeneous OL, OL with dysplasia, and OL localized to the tongue have higher transformation rates.

Occupational exposure to whole body vibrations and birth outcomes - A nationwide cohort study of Swedish women.

BACKGROUND: More women in reproductive ages are entering occupations where exposure to whole body vibrations (WBV) is common (e.g. in transportation and construction). Previous studies based on self-assessed exposure suggest increased risks of adverse birth outcomes, but it is unclear at what exposure levels and if the current exposure guidelines are appropriate during pregnancy. OBJECTIVES: To investigate whether occupational WBV-exposure increases the risk of preterm birth, low birth weight, and/or small-for-gestational age, in a large, nationwide, prospective, cohort study. DESIGN: The Fetal Air Pollution Exposure cohort (FAIR) was formed by merging data from multiple, national registers, and the present study includes singletons born 1994-2014 to working women in Sweden (n = 1,091,080 births). WBV-exposure was assessed quantitatively using a job-exposure matrix based on measurements, and calculated odds ratios were adjusted for potential confounders such as smoking and BMI, and other occupational exposures like noise, combustion particles, and physically and psychologically strenuous work. Data on absence from work (full-/part time, sick leave, parental leave, etc.) was also used. RESULTS: Exposure to WBV during pregnancy, among women with low absence from work (n = 476,419), was associated with an increased risk of preterm birth, below the occupational exposure limit (1.15 m/s2). Compared to unexposed mothers, the OR was 1.38 (95% CI: 1.05, 1.83) for exposure ≥0.5 m/s2, corresponding to an increase from 47/1000 cases to 65/1000 cases. No increased risk was found for small-for-gestational age. CONCLUSIONS: Exposure to WBV was associated with an increased risk of preterm birth. The results suggest that the current permissible exposure and action levels for WBV-exposure do not adequately protect pregnant women with continuous exposure.

How often is a low Apgar score the result of substandard care during labour?

Please cite this paper as: Berglund S, Pettersson H, Cnattingius S, Grunewald C. How often is a low Apgar score the result of substandard care during labour? BJOG 2010;117:968-978. Objective To increase our knowledge of the occurrence of substandard care during labour. Design A population-based case-control study. Setting Stockholm County. Population Infants born in the period 2004-2006 in Stockholm County. Methods Cases and controls were identified from the Swedish Medical Birth Register, had a gestational age of >/=33 complete weeks, had planned for a vaginal delivery, and had a normal cardiotocographic (CTG) recording on admission. We compared 313 infants with an Apgar score of <7 at 5 minutes of age with 313 randomly selected controls with a full Apgar score, matched for year of birth. Main outcome measure Substandard care during labour. Results We found that 62% of cases and 36% of controls were subject to some form of substandard care during labour. In half of the cases and in 12% of the controls, CTG was abnormal for >/=45 minutes before birth. Fetal blood sampling was not performed in 79% of both cases and controls, when indicated. Oxytocin was provided without signs of uterine inertia in 20% of both cases and controls. Uterine contractions were hyperstimulated by oxytocin in 29% of cases and in 9% of controls, and the dose of oxytocin was increased despite abnormal CTG in 19% and 6% of cases and controls, respectively. Assuming that substandard care is a risk factor for low Apgar score, we estimate that up to 42% of the cases could be prevented by avoiding substandard care. Conclusions There was substandard care during labour of two-thirds of infants with a low Apgar score. The main reasons for substandard care were related to misinterpretation of CTG, not acting on an abnormal CTG in a timely fashion and incautious use of oxytocin.

How often is a low Apgar score the result of substandard care during labour?

OBJECTIVE: To increase our knowledge of the occurrence of substandard care during labour. DESIGN: A population-based case-control study. SETTING: Stockholm County. POPULATION: Infants born in the period 2004-2006 in Stockholm County. METHODS: Cases and controls were identified from the Swedish Medical Birth Register, had a gestational age of +/-33 complete weeks, had planned for a vaginal delivery, and had a normal cardiotocographic (CTG) recording on admission. We compared 313 infants with an Apgar score of < 7 at 5 minutes of age with 313 randomly selected controls with a full Apgar score, matched for year of birth. MAIN OUTCOME MEASURE: Substandard care during labour. RESULTS: We found that 62% of cases and 36% of controls were subject to some form of substandard care during labour. In half of the cases and in 12% of the controls, CTG was abnormal for > or = 45 minutes before birth. Fetal blood sampling was not performed in 79% of both cases and controls, when indicated.Oxytocin was provided without signs of uterine inertia in 20% of both cases and controls. Uterine contractions were hyperstimulated by oxytocin in 29% of cases and in 9% of controls, and the dose of oxytocin was increased despite abnormal CTG in 19% and 6% of cases and controls, respectively. Assuming that substandard care is a risk factor for low Apgar score, we estimate that up to 42% of the cases could be prevented by avoiding substandard care. CONCLUSIONS: There was substandard care during labour of two thirds of infants with a low Apgar score. The main reasons for substandard care were related to misinterpretation of CTG, not acting on an abnormal CTG in a timely fashion and incautious use of oxytocin.

Internal dose assessment of 148Gd using isotope ratios of gamma-emitting 146Gd or 153Gd in accidently released spallation target particles.

The pure alpha emitter 148Gd may have a significant radiological impact in terms of internal dose to exposed humans in case of accidental releases from a spallation source using a tungsten target, such as the one to be used in the European Spallation Source (ESS). In this work we aim to present an approach to indirectly estimate the whole-body burden of 148Gd and the associated committed effective dose in exposed humans, by means of high-resolution gamma spectrometry of the gamma-emitting radiogadolinium isotopes 146Gd and 153Gd that are accompanied by 148Gd generated from the operation of the tungsten target. Theoretical minimum detectable whole-body activity (MDA) and associated internal doses from 148Gd are calculated using a combination of existing biokinetic models and recent computer simulation studies on the generated isotope ratios of 146Gd/148Gd and 153Gd/148Gd in the ESS target. Of the two gamma-emitting gadolinium isotopes, 146Gd is initially the most sensitive indicator of the presence of 148Gd if whole-body counting is performed within a month after the release, using the twin photo peaks of 146Gd centered at 115.4 keV (MDA < 1 Bq for ingested 148Gd, and < 25 Bq for inhaled 148Gd). The corresponding minimum detectable committed effective doses will be less than 1 µSv for ingested 148Gd, but substantially higher for inhaled 148Gd (up to 0.3 mSv), depending on operation time of the target prior to the release. However, a few months after an atmospheric release, 153Gd becomes a much more sensitive indicator of body burdens of 148Gd, with a minimum detectable committed effective doses ranging from 18 to 77 µSv for chronic ingestion and between 0.65 to 2.7 mSv for acute inhalation in connection to the release. The main issue with this indirect method for 148Gd internal dose estimation, is whether the primary photon peaks from 146 and 153Gd can be detected undisturbed. Preliminary simulations show that nuclides such as 182Ta may potentially create perturbations that could impair this evaluation method, and which impact needs to be further studied in future safety assessments of accidental target releases.