Search

Irene Sandven,1 Jan Eritsland,2 Michael Abdelnoor3,4 1Oslo Centre for Biostatistics and Epidemiology (OCBE), Oslo University Hospital, Oslo, Norway; 2Department of Cardiology, Oslo University Hospital, Oslo, Norway; 3Centre of Clinical Heart Research, Oslo University Hospital, Oslo, Norway; 4Epidemiology and Biological Statistics, Independent Health Research Unit, Oslo, NorwayCorrespondence: Irene Sandven Email uxsair@ous-hf.noObjective: To evaluate the efficacy of remote ischemic conditioning (RIC) as compared to no conditioning on clinical endpoints in acute coronary syndromes (ACS) patients undergoing percutaneous coronary intervention (PCI).Design: Systematic review of randomized clinical trials (RCTs).Material and Methods: Literature was searched up to September 13, 2019, and we identified a total of 13 RCTs. The efficacy of RIC on incidence of clinical events during follow-up was quantified by the rate ratio (RR) with its 95% confidence interval (CI), and we used fixed and random effects models to synthetize the results. Small-study effect was evaluated, and controlled for by the trim-and-fill method. Heterogeneity between studies was examined by subgroup and meta-regression analyses. The risk of false-positive results in meta-analysis was evaluated by trial sequential analysis (TSA).Results: Pooled analysis of 13 trials (7183 patients) showed that RIC compared to no conditioning revealed a non-significant risk reduction on endpoint mortality (RR=0.81, 95% CI: 0.56– 1.17) during a median follow-up time of 1 year (range: 0.08– 3.8) with low heterogeneity (I2=16%). Controlling for small-study effect showed no efficacy of RIC (adjusted RR: 1.03, 95% CI: 0.66– 1.59). Pooled effect of RIC on the incidence of myocardial infarction (MI) from 11 trials (6996 patients) was non-significant too (RR=0.85, 95% CI: 0.62– 1.18), with no observed heterogeneity (I2=0%) or small-study effect. A similar lack of efficacy was found in endpoint congestive heart failure (CHF) from 6 trials including 6098 patients (RR=0.71, 95% CI: 0.44– 1.15), with moderate heterogeneity (I2=30%). TSAs showed that the pooled estimates from the cumulative meta-analyses were true negative with adequate power.Conclusion: Evidence from this updated systematic review demonstrates no beneficial effect of RIC on the incidence of clinical endpoint mortality, MI and CHF during a median follow-up of 1 year in ACS patients undergoing PCI.Keywords: remote ischemic conditioning, mortality, myocardial infarction, congestive heart failure, meta-analysis, trial sequential analysis

Anne H Krog,1,2 Mehdi Sahba,3 Erik M Pettersen,4 Irene Sandven,5 Per M Thorsby,1,6 Jørgen J Jørgensen,1,2 Jon O Sundhagen,2 Syed SS Kazmi2 1Institute of Clinical Medicine, University of Oslo, 2Department of Vascular Surgery, Division of Cardiovascular and Pulmonary Diseases, Oslo University Hospital, Oslo, 3Department of Vascular Surgery, Østfold Central Hospital, Fredrikstad, 4Department of Vascular Surgery, Sørlandet Hospital HF, Kristiansand, 5Oslo Center for Biostatistics and Epidemiology (OCBE), 6Hormone Laboratory, Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway Purpose: Minimally invasive surgical techniques have been shown to reduce the inflammatory response related to a surgical procedure. The main objective of our study was to measure the inflammatory response in patients undergoing a totally laparoscopic versus open aortobifemoral bypass surgery. This is the first randomized trial on subjects in this population.Patients and methods: This is a substudy of a larger randomized controlled multicenter trial (Norwegian Laparoscopic Aortic Surgery Trial). Thirty consecutive patients with severe aortoiliac occlusive disease eligible for aortobifemoral bypass surgery were randomized to either a totally laparoscopic (n=14) or an open surgical procedure (n=16). The inflammatory response was measured by perioperative monitoring of serum interleukin-6 (IL-6), IL-8, and C-reactive protein (CRP) at six different time points.Results: The inflammatory reaction caused by the laparoscopic procedure was reduced compared with open surgery. IL-6 was significantly lower after the laparoscopic procedure, measured by comparing area under the curve (AUC), and after adjusting for the confounding effect of coronary heart disease (P=0.010). The differences in serum levels of IL-8 and CRP did not reach statistical significance.Conclusion: In this substudy of a randomized controlled trial comparing laparoscopic and open aortobifemoral bypass surgeries, we found a decreased perioperative inflammatory response after the laparoscopic procedure measured by comparing AUC for serum IL-6. Keywords: inflammation, vascular, laparoscopy, surgery, interleukin, C-reactive protein

M Abdelnoor,1,2 Ø A Vengen,3 O Johansen,4 I Sandven,2 AM Abdelnoor5 1Centre for Clinical Heart Research, Department of Cardiology 2Oslo Centre for Biostatistics and Epidemiology, 3Department of Cardiovascular Surgery, 4Department of Cardiology, Oslo University Hospital, Oslo, Norway; 5Department of Experimental Pathology, Immunology and Microbiology, American University of Beirut, Beirut, Lebanon Objective: We aimed to summarize the pooled frequency of mediastinitis following open-heart surgery caused by Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), and Gram-negative bacteria. Design: This study was a systematic review and a meta-analysis of prospective and retrospective cohort studies. Materials and methods: We searched the literature, and a total of 97 cohort studies were identified. Random-effect model was used to synthesize the results. Heterogeneity between studies was examined by subgroup and meta-regression analyses, considering study and patient-level variables. Small-study effect was evaluated. Results: Substantial heterogeneity was present. The estimated incidence of mediastinitis evaluated from 97 studies was 1.58% (95% confidence intervals [CI] 1.42, 1.75) and that of Gram-positive bacteria, Gram-negative bacteria, and MRSA bacteria evaluated from 63 studies was 0.90% (95% CI 0.81, 1.21), 0.24% (95% CI 0.18, 0.32), and 0.08% (95% CI 0.05, 0.12), respectively. A meta-regression pinpointed negative association between the frequency of mediastinitis and latitude of study place and positive association between the frequency of mediastinitis and the age of the patient at operation. Multivariate meta-regression showed that prospective cohort design and age of the patients and latitude of study place together or in combination accounted for 17% of heterogeneity for end point frequency of mediastinitis, 16.3% for Gram-positive bacteria, 14.7% for Gram-negative bacteria, and 23.3% for MRSA bacteria. Conclusion: Evidence from this study suggests the importance of latitude of study place and advanced age as risk factors of mediastinitis. Latitude is a marker of thermally regulated bacterial virulence and other local surgical practice. There is concern of increasing risk of mediastinitis and of MRSA in elderly patients undergoing sternotomy. Keywords: mediastinitis, sternotomy, meta-analysis

M Abdelnoor,1,2 I Sandven,1 S Limalanathan,3 J Eritsland3 1Centre of Epidemiology and Biostatistics, 2Centre of Clinical Heart Research, 3Department of Cardiology, Oslo University Hospital, Ullevål, NorwayObjective: We aimed to summarize the evidence from randomized clinical trials studies examining the efficacy of ischemic postconditioning (IPost) in ST-elevation myocardial infarction. Design: The study was a systematic review and critical appraisal, with meta-analysis of randomized clinical trials. Materials and methods: We searched the literature. A total of 21 randomized clinical trials were identified. Both fixed effect and random effects models were used to synthesize the results of individual studies. Heterogeneity between studies was examined by subgroup and random effects meta-regression analyses, considering ptient-related and study-level variables. Publication bias, or “small-study effect”, was evaluated. Results: Substantial heterogeneity was present. The random effects model pooled estimate for the outcome infarct size assessed by cardiac magnetic resonance was estimated by the standardized mean difference (SMD) =−0.06, 95% confidence interval (CI): −0.34 to 0.21, ie, no effect of IPost. For the end point infarct size, estimated by biomarkers of myocardial necrosis, an overall pooled effect was SMD =−0.58, 95% CI: −0.96 to −0.19. This effect disappeared in powered and nonbiased studies (SMD =0.03, 95% CI: −0.48 to 0.55). Finally, for the outcome left ventricular ejection fraction, SMD =0.47 95% CI: 0.20 to 0.74. Unfortunately, selection bias (small-study effect) was present. For this outcome, the meta-regression showed that both presence of hypertension and the inclusion of nonbiased studies explained 28.3% of the heterogeneity among the studies. Simulation by the “trim and fill” method, which controlled for selection bias using random effects model, diluted the effect (SMD =0.17 95% CI: −0.13 to 0.48). No effects by IPost on ST-segment resolution or on the majority of adverse clinical events were observed during follow up, except the incidence of congestive heart failure was found. Conclusion: Evidence from this study suggests no cardioprotection from IPost, on surrogate and the majority of clinical end points. A possible beneficial effect on the incidence of congestive heart failure needs to be replicated by a large clinical trial. Keywords: ischemic postconditioning, acute myocardial infarction, percutaneous coronary intervention

Objective: To investigate the association between assisted reproductive technology and severe postpartum haemorrhage.Design: Case-control study.Setting: The study was conducted in Norway; Division of Gynaecology and Obstetrics at Oslo University Hospital and Department of Obstetrics and Gynaecology at Drammen Hospital.Population: A source population including all women admitted for delivery at Oslo University Hospital and Drammen Hospital during the time period 1 January 2008 to 31 December 2011. The study population consisted of all cases of severe postpartum haemorrhage (n = 1064) and a random sample of controls (n = 2059).Methods: We used an explanatory strategy in the analysis, with multivariable logistic regression.Main Outcome Measures: Severe postpartum haemorrhage; defined as blood loss ≥1500 ml or need for blood transfusion.Results: Assisted reproductive technology was associated with an increased risk of severe postpartum haemorrhage (crude OR = 2.92; 95% CI 2.18-3.92, P < 0.001). Mode of delivery and anticoagulant medication had significant confounding effects. Strong interaction was found for multiple pregnancies. After adjusting for confounding and interaction, an increased risk was observed both in the strata of multiple pregnancies (adjusted OR = 7.00, 95% CI 2.70-18.12, P < 0.001), and in the strata of single gestation (adjusted OR = 1.58, 95% CI 1.12-2.24, P = 0.010).Conclusions: Our findings warrant an increased awareness of the risk of severe postpartum haemorrhage in women conceiving with assisted reproductive technology. Furthermore, the high risk of severe postpartum haemorrhage in the presence of a twin or triplet pregnancy is an additional argument for single embryo transfer.Tweetable Abstract: Assisted reproductive technology is associated with an increased risk of severe postpartum haemorrhage. [ABSTRACT FROM AUTHOR]

Fractional exhaled nitric oxide (FeNO) is a breath-related biomarker of eosinophilic asthma. The aim of this study was to investigate FeNO variations due to environmental or occupational exposures in respiratory healthy subjects. Overall, 14 hairdressers and 15 healthcare workers in Oslo were followed for 5 workdays. We registered the levels of FeNO after commuting and arriving at the workspace and after ≥3 h of work, in addition to symptoms of cold, commuting method, and hair treatments that were performed. Both short- and intermediate-term effects after exposure were evaluated. Environmental assessment of daily average levels of air quality particulate matter 2.5 (PM 2.5 ), particulate matter 10 (PM 10 ), nitrogen dioxide (NO 2 ), sulphur dioxide (SO 2 ), and ozone (O 3 ) indicated a covariation in ozone and FeNO in which a 35-50% decrease in ozone was followed by a near 20% decrease in FeNO with a 24-h latency. Pedestrians had significantly increased FeNO readings. Symptoms of cold were associated with a significant increase in FeNO readings. We did not find any FeNO increase of statistical significance after occupational chemical exposure to hair treatments. The findings may be of clinical, environmental and occupational importance.

Aims: Cardiovascular risk factor control is suboptimal in Europe, including Norway. The present study examined the efficacy of a multimodal primary prevention intervention programme based on the existing Norwegian health care system., Methods and Results: In this open-label randomized controlled trial, adult patients with elevated cardiovascular risk were randomly assigned to an intervention programme including a hospital-based lifestyle course and primary care follow-up or to a control group (CG). The participants were recruited between 2011 and 2015. Primary outcome was change in validated cardiovascular risk scores, national and international (NORRISK, NORRISK 2, Framingham, PROCAM) between baseline and follow-up. Secondary outcomes included major cardiovascular risk factors. After 36 months the NORRISK score was significantly improved in patients assigned to the intervention group (IG) compared to patients assigned to the CG; absolute difference in mean delta score in the IG (n = 305) compared to mean delta score in the CG (n = 296): -0.92, 95% CI: -1.48 to -0.36, P = 0.001. The results for NORRISK 2, Framingham and PROCAM showed similar significant effects. The secondary endpoints including total cholesterol and blood pressure were only minimally, and non-significantly, reduced in the IG, but the proportion of smokers (P = 0.0028) and with metabolic syndrome (P < 0.0001) were significantly reduced. A limited number of cardiovascular events were observed, IG (n = 9), CG (n = 16)., Conclusion: In subjects with elevated cardiovascular risk, a newly developed prevention programme, combining a hospital-based lifestyle course and primary care follow-up, significantly reduced cardiovascular risk scores after 36 months. This benefit appeared achievable primarily through improvements in metabolic syndrome characteristics and smoking habits.The study protocol was registered in ClinicalTrials.gov (NCT01741428)., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: We aimed to identify the aetiological distribution and the diagnostic methods for paediatric hydrocephalus across Africa, for which there is currently scarce evidence., Methods: In this systematic review and meta-analysis, we searched MEDLINE (Ovid), the Cochrane Database of Systematic Reviews (Wiley), Embase (Ovid), Global Health (Ovid), Maternity & Infant Care (Ovid), Scopus, African Index Medicus (Global Index Medicus, WHO) and Africa-Wide Information (EBSCO) from inception to Nov 29, 2021. We included studies from any African country reporting on the distribution of hydrocephalus aetiology in children aged 18 years and younger, with no language restrictions. Hydrocephalus was defined as radiological evidence of ventriculomegaly or associated clinical symptoms and signs of the disorder, or surgical treatment for hydrocephalus. Exclusion criteria were studies only reporting on one specific subgroup or one specific cause of hydrocephalus. We also excluded conference and meetings abstracts, grey literature, editorials, commentaries, historical reviews, systematic reviews, case reports and clinical guidelines, as well as studies on non-humans, fetuses, or post-mortem reports. The proportions of postinfectious hydrocephalus, non-postinfectious hydrocephalus, and hydrocephalus related to spinal dysraphism were calculated using a random-effects model. Additionally, we included a category for unclear cases. Diagnostic methods were described qualitatively. To assess methodological study quality, we applied critical appraisal checklists provided by the Joanna Briggs Institute. The study was registered in Prospero (CRD42020219038)., Findings: Our search yielded 3783 results, of which 1880 (49·7%) were duplicates and were removed. The remaining 1903 abstracts were screened and 122 (6·4%) full articles were sought for retrieval; of these, we included 38 studies from 18 African countries that studied a total of 6565 children. The pooled proportion of postinfectious hydrocephalus was 28% (95% CI 22-36), non-postinfectious hydrocephalus was 21% (95% CI 13-30), and of spinal dysraphism was 16% (95% CI 12-20), with substantial heterogeneity. The pooled proportion of hydrocephalus of unclear aetiology was 20% (95% CI 13-28)., Interpretation: Our findings suggest that postinfectious hydrocephalus is the single most common cause of paediatric hydrocephalus in Africa. For targeted investments to be optimal, there is a need for consensus regarding the aetiological classification of hydrocephalus and improved access to diagnostic services., Funding: Rikshospitalet, Oslo University Hospital, Oslo, Norway., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Glove-related hand urticaria is probably underdiagnosed and is an important differential diagnosis in suspected cases of contact allergy., Case Presentation: A nurse in her twenties presented with recurrent immediate-onset erythematous eruption with burning sensation on the dorsal hands after wearing disposable gloves. This occurred irrespective of the type of disposable gloves used. Patch testing, serological analysis for latex IgE and prick tests with latex and different glove materials all gave negative results. Dermographism was demonstrated on her back, and symptoms were reproduced after wearing disposable gloves. Symptoms were less severe when a looser-fitting glove was worn. She was treated with antihistamines and intensified barrier cream, and was recommended to wear loose-fitting gloves at work. She experienced no effect from antihistamines but some improvement from barrier protection., Interpretation: Glove-related hand urticaria should be suspected in healthcare workers with immediate-onset urticarial reaction to multiple glove types, negative allergy tests and the presence of dermographism. Symptoms may be reproduced when wearing a tight-fitting glove.

Background: The evidence of the long-term effects of multiple lifestyle intervention on cardiovascular risk is uncertain. We aimed to summarize the evidence from randomized clinical trials examining the efficacy of lifestyle intervention on major cardiovascular risk factors in subjects at high cardiovascular risk., Methods: Eligible trials investigated the impact of lifestyle intervention versus usual care with minimum 24 months follow-up, reporting more than one major cardiovascular risk factor. A literature search updated April 15, 2020 identified 12 eligible studies. The results from individual trials were combined, using fixed and random effect models, using the standardized mean difference (SMD) to estimate effect sizes. Small-study effect was evaluated, and heterogeneity between studies examined, by subgroup and meta-regression analyses, considering patient- and study-level variables., Results: Small-study effect was not identified. Lifestyle intervention reduced systolic blood pressure modestly with an estimated SMD of - 0.13, 95% confidence interval (CI): - 0.21 to - 0.04, with moderate heterogeneity (I 2  = 59%), corresponding to a mean difference of approximately 2 mmHg (MD = - 1.86, 95% CI - 3.14 to - 0.57, p = 0.0046). This effect disappeared in the subgroup of trials judged at low risk of bias (SMD = 0.02, 95% CI - 0.08 to 0.11). For the outcome total cholesterol SMD was - 0.06, 95% CI - 0.13 to 0.00, with no heterogeneity (I 2  = 0%), indicating no effect of the intervention., Conclusion: Lifestyle intervention resulted in only a modest effect on systolic blood pressure and no effect on total cholesterol after 24 months. Further lifestyle trials should consider the challenge of maintaining larger long-term benefits to ensure impact on cardiovascular outcomes.

Objective: The aim was to summarise the evidence from published epidemiological studies investigating the efficacy of statin therapy on long term survival in patients after abdominal aortic aneurysm (AAA) repair., Data Sources: This study was a systematic review with critical appraisal and meta-analysis of observational studies., Review Methods: A systematic literature search was carried out throughout February 2020, revealing 14 eligible cohort studies of which 11 were judged to be of high quality. A random effects model was used to synthesise results, and heterogeneity between studies examined by subgroup and meta-regression analyses considering patient and study related variables. Small study effect was evaluated., Results: The pooled estimate showed that statin treatment among 69 790 AAA patients with a median follow up of 3.1 years was associated with a 35% relative reduction in total mortality (rate ratio 0.65, 95% confidence interval 0.57-0.73) with moderate heterogeneity (I 2  = 68%) and no small study effect., Conclusion: Evidence from this systematic review indicates a beneficial effect of statins on long term survival in patients treated by AAA repair., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Aims: Falls among inpatients are common. The method used by The Norwegian Patient Safety Campaign to measure the adverse events is the Global Trigger Tool, which does not look at the causation for falls. This study was aimed at investigating major risk factors for falls in the hospital setting., Methods: This retrospective case-control study was conducted at Telemark Hospital in Norway, in the period from September 2012 to August 2014. A total of 842 patients from three wards were included, whereof 172 cases had experienced one or more fall(s) during hospitalisation and 670 random controls had not fallen. Data were analysed according to a pragmatic strategy., Results: Compared with patients who did not fall, patients who fell were 21 times more likely to have poor balance (OR = 21.50, 95% CI: 10.26-45.04) and 19 times more likely to have very poor balance (OR = 19.62, 95% CI: 9.55-40.27), twice as likely to be men (OR = 1.82, 95% CI: 1.24-2.68), and 50% increased probability of fall with every 10 year increase of age (OR = 1.51, 95% CI: 1.34-1.69). Furthermore, the patients who fell were more likely to use antidepressant drugs (OR = 3.85, 95% CI: 1.09-13.63), antipsychotic drugs (OR = 3.27, 95% CI: 1.94-5.51), anxiolytic/hypnotic drugs (OR = 1.80, 95% CI: 1.22-2.67) and antiepileptic drugs (OR = 1.13, 95% CI: 1.11-4.06) than patients who did not fall., Conclusions: During hospital stay, patients who fell had a higher risk profile than patients who did not fall. Clinicians should work to improve patients' safety and reduce the risk of falls by accurately assessing balance and mobility as a form of primary prevention. We recommend that a review of the patient medications should be conducted upon falling, as a form of a secondary preventive strategy against falls., (© 2019 The Authors. Scandinavian Journal of Caring Sciences published by John Wiley & Sons Ltd on behalf of Nordic College of Caring Science.)

Objective. We aimed to summarize the evidence from observational studies examining the risk factors of the incidence of mediastinitis in open heart surgery. Design. The study was a systematic review and meta-analysis of cohorts and case-control studies. Material and methods. We searched the literature and 74 studies with at least one risk factor were identified. Both fixed and random effects models were used. Heterogeneity between studies was examined by subgroup and meta-regression analysis. Publication bias or small study effects were evaluated and corrected by limit meta-analysis. Results. When correcting for small study effect, presence of obesity as estimated from 43 studies had Odds Ratio OR = 2.26. (95% CI: 2.17-2.36). This risk was increasing with decreasing latitude of study place. Presence of diabetes mellitus from 63 studies carried an OR = 1.90 (95% CI: 1.59-2.27). Presence of Chronic Obstructive Pulmonary Disease (COPD) from 30 studies had an OR = 2.59 (95% CI: 2.22-2.85). Presence of bilateral intramammary graft (BIMA) from 23 studies carried an OR = 2.54 (95% CI: 2.07-3.13). This risk was increasing with increasing frequency of female patients in the study population. Conclusion. Evidence from this study showed the robustness of the risk factors in the pathogenesis of mediastinitis. Preventive measures can be implemented for reducing obesity, especially in lower latitude countries. Furthermore, it is mandatory to monitor perioperative hyperglycemias with continuous insulin infusion. Use of skeletonized BIMA carries higher risk of mediastinitis especially in female patients without evidence of beneficial effect on survival for the time being.

Aims: Guidelines concerning β-blocker treatment following acute myocardial infarction (AMI) are based on studies undertaken before the implementation of reperfusion and secondary prevention therapies. We aimed to estimate the effect of oral β-blockers on mortality in contemporary post-AMI patients with low prevalence of heart failure and/or reduced left ventricular ejection fraction., Methods and Results: A random effects model was used to synthetize results of 16 observational studies published between 1 January 2000 and 30 October 2017. Publication bias was evaluated, and heterogeneity between studies examined by subgroup and random effects meta-regression analyses considering patient-related and study-level variables. The pooled estimate showed that β-blocker treatment [among 164 408 (86.8%) patients, with median follow-up time of 2.7 years] was associated with a 26% reduction in all-cause mortality [rate ratio (RR) 0.74, 95% confidence interval (CI) 0.64-0.85] with moderate heterogeneity (I2 = 67.4%). The patient-level variable mean age of the cohort explained 31.5% of between study heterogeneity. There was presence of publication bias, or small study effect, and when controlling for bias by the trim and fill simulation method, the effect disappeared (adjusted RR 0.90, 95% CI 0.77-1.04). Also, small study effect was demonstrated by a cumulative meta-analysis starting with the largest study showing no effect, with increasing effect as the smaller studies were accumulated., Conclusion: Evidence from this study suggests that there is no association between β-blockers and all-cause mortality. A possible beneficial effect in AMI survivors needs to be tested by large randomized clinical trials.

Background: The 30-day all-cause readmission rate after surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR) vary substantially. We conducted a systematic review and meta-analysis to examine the overall incidence, causes, and risk factors of 30-day all-cause readmission rate after SAVR and TAVR., Methods: Eight medical research databases were searched; Cochrane, Medline, Embase, UpToDate, PROSPERO, National Guideline Clearinghouse, SweMed and Oria. We followed The Preferred Reporting Items for Systematic reviews and Meta-analysis (PRISMA) for this study., Results: Thirty-three articles were included in the systematic review, 32 of which were appropriate for the meta-analysis. Overall, 17% (95% CI: 16-18%) of patients in the SAVR group, and 16% (95% CI: 15-18%) in the TAVR groups were readmitted within 30 days. Heart failure, arrhythmia, infection, and respiratory problems were the most frequent causes of all-cause readmission after SAVR and TAVR. Most frequent reported prior risk factors for all-cause readmission following TAVR were diabetes, chronic lung disease/chronic obstructive pulmonary disease, atrial fibrillation, kidney problems, and transapical approach/nonfemoral access. For SAVR, no risk factors for 30-day all-cause readmission were reported in the literature to date., Conclusion: In conclusion, the overall proportion of 30-day all-cause readmission after SAVR and TAVR are high. Interventions to prevent avoidable readmissions ought to be developed and implemented., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The chewing of the leaves of Catha edulis (khat) has been implicated in the development of liver disease, but no controlled observations have been undertaken. The objective of the present study was to determine whether khat chewing is associated with development of chronic liver disease (CLD). A case-control study was conducted at two public hospitals in Harar, Ethiopia, between April 2015 and April 2016. A consecutive sample of 150 adult hospital attendees with CLD were included as cases, and 300 adult hospital attendees without clinical or laboratory evidence of CLD were included as controls. Khat consumption was quantified in "khat years"; 1 khat year was defined as daily use of 200 g of fresh khat for 1 year. A logistic regression model was used to control for confounders. There was a significant association between chewing khat and the risk for developing CLD (crude odds ratio, 2.64; 95% confidence interval [CI], 1.56-4.58). In men, this risk, following adjustment for age, alcohol use, and chronic hepatitis B/C infection, increased with increasing khat exposure; thus, compared to never users the adjusted odds ratios were for low khat exposure 3.58 (95% CI 1.05-12.21), moderate khat exposure 5.90 (95% CI 1.79-19.44), and high khat exposure 13.03 (95% CI 3.61-47.02). The findings were robust in a post hoc sensitivity analysis in which individuals with identifiable risk factors for CLD were excluded., Conclusion: A significant association was observed between chewing khat and the risk for developing CLD, and in men the association was strong and dose-dependent, suggesting a causal relationship; as the prevalence of khat chewing is increasing worldwide, these findings have major public health implications. (Hepatology 2018;68:248-257)., (© 2018 by the American Association for the Study of Liver Diseases.)

Background In contemporary atrial fibrillation trials most deaths are cardiac related, whereas stroke and bleeding represent only a small subset of deaths. We aimed to evaluate the long-term risk of cardiac events and all-cause mortality in individuals with atrial fibrillation compared to no atrial fibrillation. Design A systematic review and meta-analysis of studies published between 1 January 2006 and 21 October 2016. Methods Four databases were searched. Studies had follow-up of at least 500 stable patients for either cardiac endpoints or all-cause mortality for 12 months or longer. Publication bias was evaluated and random effects models were used to synthesise the results. Heterogeneity between studies was examined by subgroup and meta-regression analyses. Results A total of 15 cohort studies was included. Analyses indicated that atrial fibrillation was associated with an increased risk of myocardial infarction (relative risk (RR) 1.54, 95% confidence interval (CI) 1.26-1.85), all-cause mortality (RR 1.95, 95% CI 1.50-2.54) and heart failure (RR 4.62, 95% CI 3.13-6.83). Coronary heart disease at baseline was associated with a reduced risk of myocardial infarction and explained 57% of the heterogeneity. A prospective cohort design accounted for 25% of all-cause mortality heterogeneity. Due to there being fewer than 10 studies, sources of heterogeneity were inconclusive for heart failure. Conclusions Atrial fibrillation seems to be associated with an increased risk of subsequent myocardial infarction in patients without coronary heart disease and an increased risk of, all-cause mortality and heart failure in patients with and without coronary heart disease.

Minimally invasive surgery seems to reduce hormonal stress response to surgery, but has not previously been examined in major abdominal vascular surgery. Aortic cross-clamping time and operation time is known to be longer in the totally laparoscopic aortobifemoral bypass (LABF) as compared to open aortobifemoral bypass (OABF). The main objective of our study was to measure the hormonal stress response during surgery and aortic cross-clamping in patients undergoing a totally laparoscopic versus an open aortobifemoral bypass. This was a sub-study of a larger randomized controlled multicentre trial. Thirty consecutive patients with severe aortoiliac occlusive disease were randomized to either a laparoscopic (LABF) or an open (OABF) procedure. The surgical stress response was measured by perioperative monitoring of adrenocorticotropic hormone (ACTH), aldosterone, metanephrine and cortisol at eight different time-points. During surgery. there was an increase in all humoral stress markers in both groups. The analysis of covariance showed increased levels of cortisol and ACTH in open group at 24 h time-point as compared to the baseline and this difference was statistically significant between the two groups, which indicate an earlier return to baseline levels in the laparoscopic group. Results from the General Estimated Equations (GEE) model indicate that LABF generates a lower level of metanephrine and higher level of aldosterone as compared to OABF. In conclusion, although they have higher levels of ACTH, aldosterone and cortisol during surgery, the patients operated with a laparoscopic aortobifemoral bypass achieve earlier hormonal homeostasis after surgery compared to open aortobifemoral bypass.

Background: In high-income countries, the incidence of severe postpartum hemorrhage (PPH) has increased. This has important public health relevance because severe PPH is a leading cause of major maternal morbidity. However, few studies have identified risk factors for severe PPH within a contemporary obstetric cohort., Methods: We performed a case-control study to identify risk factors for severe PPH among a cohort of women who delivered at one of three hospitals in Norway between 2008 and 2011. A case (severe PPH) was classified by an estimated blood loss ≥1500 mL or the need for blood transfusion for excessive postpartum bleeding. Using logistic regression, we applied a pragmatic strategy to identify independent risk factors for severe PPH., Results: Among a total of 43,105 deliveries occurring between 2008 and 2011, we identified 1064 cases and 2059 random controls. The frequency of severe PPH was 2.5% (95% confidence interval (CI): 2.32-2.62). The most common etiologies for severe PPH were uterine atony (60%) and placental complications (36%). The strongest risk factors were a history of severe PPH (adjusted OR (aOR) = 8.97, 95% CI: 5.25-15.33), anticoagulant medication (aOR = 4.79, 95% CI: 2.72-8.41), anemia at booking (aOR = 4.27, 95% CI: 2.79-6.54), severe pre-eclampsia or HELLP syndrome (aOR = 3.03, 95% CI: 1.74-5.27), uterine fibromas (aOR = 2.71, 95% CI: 1.69-4.35), multiple pregnancy (aOR = 2.11, 95% CI: 1.39-3.22) and assisted reproductive technologies (aOR = 1.88, 95% CI: 1.33-2.65)., Conclusions: Based on our findings, women with a history of severe PPH are at highest risk of severe PPH. As well as other established clinical risk factors for PPH, a history of severe PPH should be included as a risk factor in the development and validation of prediction models for PPH.

Background and Aims: Single-shot spinal with bupivacaine plus fentanyl or sufentanil is commonly used as analgesia during labour, but the short duration limits the clinical feasibility. Different drugs have been added to prolong the analgesic duration. The additional effect of intra-thecal morphine has been studied during labour pain as well as after surgery. We assessed whether adding morphine to intra-thecal bupivacaine+fentanyl or sufentanil prolongs pain relief during labour., Methods: Meta-analysis of placebo-controlled randomized clinical trials of analgesia prolongation after single-shot intrathecal morphine ≤250μg during labour when given in combination with bupivacaine+fentanyl or sufentanil. After identifying 461 references, 24 eligible studies were evaluated after excluding duplicate publications, case reports, studies of analgesia after caesarean delivery, and epidural labour analgesia. Mean duration in minutes was the primary outcome measure and was included in the calculation of the standardized mean difference. Duration was defined as the time between a single shot spinal until patient request of rescue analgesia. All reported side effects were registered. Results of individual trials were combined using a random effect model. Cochrane tool was used to assess risk of bias., Results: Five randomized placebo-controlled clinical trials (286 patients) were included in the meta-analysis. A dose of 50-250μg intrathecal morphine prolonged labour analgesia by a mean of 60.6min (range 3-155min). Adding morphine demonstrated a medium beneficial effect as we found a pooled effect of standardized mean difference=0.57 (95% CI: -0.10 to 1.24) with high heterogeneity (I 2 =88.1%). However, the beneficial effect was statistically non-significant (z=1.66, p=0.096). The lower-bias trials showed a small statistically non-significant beneficial effect with lower heterogeneity. In influential analysis, that excluded one study at a time from the meta-analysis, the effect size appears unstable and the results indicate no robustness of effect. Omitting the study with highest effects size reduces the pooled effect markedly and that study suffers from inadequate concealment of treatment allocation and blinding. Trial quality was generally low, and there were too few trials to explore sources of heterogeneity in meta-regression and stratified analyses. In general, performing meta-analyses on a small number of trials are possible and may be helpful if one is aware of the limitations. As few as one more placebo-controlled trial would increase the reliability greatly., Conclusions: Evidence from this systematic review suggests a possible beneficial prolonging effect of adding morphine to spinal analgesia with bupivacaine+fentanyl or +sufentanil during labour. The study quality was low and heterogeneity high. No severe side effects were reported. More adequately-powered randomized trials with low bias are needed to determine the benefits and harms of adding morphine to spinal local anaesthetic analgesia during labour., Implications: Epidural analgesia is documented as the most effective method for providing pain relief during labour, but from a global perspective most women in labour have no access to epidural analgesia. Adding morphine to single shot spinal injection of low dose bupivacaine, fentanyl or sufentanil may be efficacious but needs to be investigated., (Copyright © 2016 Scandinavian Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)

Introduction: Internal design flaws in previous reports of pregnancies following kidney transplantation have been outlined, and the need for a validation has been stated. The aim of this study was to collect information about obstetrical and neonatal outcomes in all Norwegian pregnancies following maternal kidney transplantation, and to compare these data with the general Norwegian population., Material and Methods: A retrospective cohort study based on 1 272 000 deliveries in Norway between 1969 and 2013. All data were collected from medical records. From the source population, we compared 119 first deliveries in kidney transplanted women with 238 first deliveries in nontransplanted women. An explanatory strategy was used in the analysis., Results: The risk of preeclampsia was significantly increased in kidney-transplanted women compared with nontransplanted women (adjusted incidence rate ratio: 6.06, 95% confidence interval 3.18-11.55). Additionally, preeclampsia in kidney-transplanted women was early onset (diagnosed <34 gestational weeks) in half of the cases. There were also persistent risks of cesarean delivery (adjusted incidence rate ratio 4.14, 95% confidence interval 2.56-6.66), preterm delivery (adjusted incidence rate ratio 4.45, 95% confidence interval 2.13-9.30) and a birthweight below the 10th centile (22.7% vs. 9.7%) in the kidney-transplanted group. A high proportion (63%) of the kidney-transplanted women with chronic hypertension developed preeclampsia., Conclusions: Using consistent diagnostic criteria, this study shows high rates of maternal and neonatal complications in pregnancies following kidney transplantation. In particular, we reveal a high rate of early-onset preeclampsia requiring operative preterm delivery, conferring long-term risks on both the mother and child., (© 2016 Nordic Federation of Societies of Obstetrics and Gynecology.)

Measurements of serum thyroglobulin (Tg) with sensitive immunoassays are of great importance for the management of patients with differentiated thyroid carcinomas. However, interference of circulating autoantibodies to Tg (hTgAb) hampers the usefulness of most assays. We have produced a panel of monoclonal antibodies (mAbs) selected to bind Tg in the presence of Tg autoantibodies and developed a sensitive immunoassay for Tg with minor interference by hTgAbs. The antibodies were characterized by cross-inhibition and immunoassay combination studies, as well as affinity estimation. The within-run and total imprecision of the assay were determined with 2664 samples in 60 separate runs. The most sensitive assay combination with superior protection against autoantibodies consisted of two solid phase mAbs and two tracer mAbs with distinct binding sites. The assay was linear and displayed a wide dynamic range up to 1342 μg/l with a functional sensitivity of 0.1 μg/l and a total imprecision of less than 10 %. There was good agreement between the new high sensitive immunofluorometric assay (IFMA) and two well-established Tg assays from Brahms Kryptor and Roche Diagnostics. Mean difference between the new IFMA and the Kryptor assay was 0.059 μg/l with a 95 % confidence interval of -0.032 to 0.151 μg/l, whereas the mean difference between the new IFMA and the Roche assay was -0.80 μg/l with a 95 % confidence interval of -1.24 to -0.35 μg/l.

Purpose: To compare benefits and harms of low molecular weight heparin (LMWH) versus unfractionated heparin (UFH) as thromboprophylaxis in intensive care unit (ICU) patients., Methods: We conducted a systematic review with meta-analysis and trial sequential analysis (TSA) of randomised controlled trials (RCTs) comparing LMWH with UFH as thromboprophylaxis in adult ICU patients. We searched Ovid Medline, PubMed, Embase, Cochrane Library, UpToDate, Guidelines International Network, PROSPERO and the metaRegister of Controlled Trials through 3 December 2014. Random effects risk ratios (RR) and 95% confidence intervals (CI) were derived for the endpoints deep vein thrombosis (DVT), pulmonary embolism (PE), major bleeding, mortality and net clinical benefit (any DVT, any PE, major bleeding and/or mortality)., Results: Eight RCTs (5567 patients) were included, whereof two were considered to have overall low risk of bias. Pooled analyses showed that LMWH compared with UFH reduced the risk of any DVT (RR 0.84, 95% CI 0.71-0.98, p = 0.03) and resulted in a net clinical benefit (RR 0.90, 95% CI 0.83-0.97, p = 0.01). There was no statistically significant difference in the risk of any PE (RR 0.65, 95% CI 0.41-1.03, p = 0.06), major bleeding (RR 0.99, 95% CI 0.77-1.28, p = 0.96) or mortality (RR 0.93, 95% CI 0.78-1.12, p = 0.43). TSA supported the results of the conventional analysis on the outcome net clinical benefit but not on risk of any DVT., Conclusions: Evidence from this systematic review revealed a beneficial effect of LMWH compared with UFH when used as thromboprophylaxis in ICU patients.

Infection by Toxoplasma gondii may lead to complications in the foetus if the mother suffers from primary infection during pregnancy. Previously infected women have produced toxoplasma-specific IgG antibodies. The most recent study on prevalence of toxoplasma IgG in the Norwegian pregnant population was conducted 20 years ago. The present study is part of a research programme initiated by the Norwegian Institute of Public Health. We aimed to update the knowledge regarding the prevalence of toxoplasma IgG among pregnant women in Norway. In this cross-sectional study, sera from 1922 pregnant women in Buskerud (992) and Sør-Trøndelag counties (930) in Norway were collected consecutively. The presence of toxoplasma IgG was identified by values ≥8 IU/mL using an ELISA test. The overall prevalence of toxoplasma IgG seropositivity was 9.3% (95% CI 8.1-10.7); Sør-Trøndelag 10.4% (95% CI 8.6-12.6) and Buskerud 8.3% (95% CI 6.7-10.2). There was no difference between the counties (p = 0.13), and the result did not differ from prevalences found in 1974 (12.1%) and 1994 (10.7%). We found a higher prevalence among women ≥40 years (OR 2.65, 95% CI 1.30-5.42). The prevalence of toxoplasma IgG among pregnant women in Norway is low and has been stable during the last decades., (© 2015 APMIS. Published by John Wiley & Sons Ltd.)

Migraine with aura is associated with an increased incidence of stroke and cardiovascular disease, but the biological mechanisms are poorly understood. This study examined the incidence of metabolic syndrome and its relationship to migraine with and without aura and to nonmigraine headache. In the population-based the Nord-Trøndelag Health Study (HUNT), 19,895 individuals were followed for the development of metabolic syndrome, with a median follow-up time of 11.3 years. Headache diagnoses were based on a validated headache questionnaire, and metabolic syndrome was based on a modified version of the National Cholesterol Education Program's Adult Treatment Panel (ATP) III criteria, using objective anthropometric measurements and blood biochemistry. Using the Poisson regression model, migraine with aura was associated with an increased risk for developing metabolic syndrome. The effect was modified by smoking, with an adjusted incident risk ratio (IRR) among smokers of 2.10 (95% CI 1.53-2.89) and among nonsmokers of 1.39 (95% CI 1.03-1.86), when compared to headache-free controls. A moderate risk increase was seen for migraine without aura (IRR 1.26, 95% CI 1.12-1.42) and nonmigraine headache (IRR 1.22, 95% CI 1.13-1.32), not modified by smoking. The results suggest that traditional risk factors may be one of the mechanisms through which migraine with aura is linked to an increased risk for cardiovascular disease. A heightened vigilance concerning cardiovascular risk factors in this patient group may be warranted., (Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)

Community-acquired urinary tract infection (CA-UTI) is the most common infection caused by extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae, but the clinical epidemiology of these infections in low prevalence countries is largely unknown. A population based case-control study was conducted to assess risk factors for CA-UTI caused by ESBL-producing E. coli or K. pneumoniae. The study was carried out in a source population in Eastern Norway, a country with a low prevalence of infections caused by ESBL-producing Enterobacteriaceae. The study population comprised 100 cases and 190 controls with CA-UTI caused by ESBL-producing and non-ESBL-producing E. coli or K. pneumoniae, respectively. The following independent risk factors of ESBL-positive UTIs were identified: Travel to Asia, The Middle East or Africa either during the past six weeks (Odds ratio (OR) = 21; 95% confidence interval (CI): 4.5-97) or during the past 6 weeks to 24 months (OR = 2.3; 95% CI: 1.1-4.4), recent use of fluoroquinolones (OR = 16; 95% CI: 3.2-80) and β-lactams (except mecillinam) (OR = 5.0; 95% CI: 2.1-12), diabetes mellitus (OR = 3.2; 95% CI: 1.0-11) and recreational freshwater swimming the past year (OR = 2.1; 95% CI: 1.0-4.0). Factors associated with decreased risk were increasing number of fish meals per week (OR = 0.68 per fish meal; 95% CI: 0.51-0.90) and age (OR = 0.89 per 5 year increase; 95% CI: 0.82-0.97). In conclusion, we have identified risk factors that elucidate mechanisms and routes for dissemination of ESBL-producing Enterobacteriaceae in a low prevalence country, which can be used to guide appropriate treatment of CA-UTI and targeted infection control measures.

Chronic musculoskeletal complaints (MSCs) are among the major health problems, and cross-sectional studies suggest an association between smoking and MSCs. The causal relationship, however, is not known. The present study is designed to assess the association between smoking and chronic MSCs, and is based on data from a large longitudinal cohort study of all inhabitants ⩾20years in Nord-Trøndelag County (Helse Undersøkelsen i Nord-Trøndelag -HUNT), conducted in 1995-97 (HUNT 2) and 2006-08 (HUNT 3). The study population consisted of 15,134 subjects without chronic MSCs and valid exposure data on smoking at baseline (HUNT 2). The outcome was defined as presence of chronic MSCs at follow-up (HUNT 3). The results show that smoking at baseline represents a 20% increased risk (IRR=1.20, 95% CI 1.14-1.27, P=0.0001) for chronic MSCs at follow-up. The risk for chronic MSCs by daily smoking decreased with increasing age up to 50years; after this, there was no significant association. The results show that modifiable risk factors like smoking should be included in public health intervention programs for MSCs., (Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)

Introduction: After completed anticoagulant treatment for acute VTE, both the subsequent mortality and risk of recurrent VTE are high, probably related to the frequent presence of serious disease in these patients. The aim of the study was to determine survival and recurrence in selected patients with good life-expectancy, and to evaluate risk factors., Methods: The 323 patients were followed for median 7.4 years (range 4.1-11.9) after cessation of anticoagulation. Survival analysis and Cox-regression were used for univariate and multivariate analysis., Results: The cumulative incidence of survival after 5 years was 93.4%. Standardised mortality ratio was 1.42 for men and 1.28 for women. Patients without a transient risk factor prior to the index VTE were associated with higher risk of mortality compared to risk of mortality in patients with a transient risk factor (hazard ratio (HR) 2.81; 95% CI 1.40-5.62). Recurrence of VTE after 5 years was 19.0%. A persistent risk factor or a spontaneous VTE was associated with higher risk of recurrence compared to a transient risk factor (HR 2.39; 95% CI 1.44-3.95). Elevated D-dimer levels increased the risk, and immobilisation prior to the index VTE reduced the risk of recurrence. Sex, age and thrombophilia were not independent risk factors for recurrence., Conclusions: Despite a low mortality rate in this selected cohort, the recurrence rate and risk factors for recurrence were similar to findings reported in unselected populations. VTE unrelated to a transient risk factor was associated with increased mortality compared to mortality in patients with a transient risk factor., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Objective: Critical appraisal of published case-control studies examining the etiology or risk factors of Hyperemesis gravidarum (HG)., Materials and Methods: We searched the Medline/PubMed database from 1966 to February 12, 2009. A total of 48 case-control studies were retrieved and each article was evaluated using a structured assessment devised for the purpose., Results: The case-control studies were published between 1978 and 2008. The majority investigated hormonal, gastrointestinal, and metabolic risk factors associated with hyperemesis gravidarum (37 studies). Selection bias and non-response received insufficient attention in many articles. Sample size varied widely with a median number of 40 cases and 42 controls. Association uncommonly was expressed by odds ratios and confidence intervals (9 studies), confounding rarely controlled for (10 studies) and few examined effect modification (2 studies)., Conclusion: We are concerned as far the inadequacies in the design, analysis, and reporting of case-control studies examining the etiology of HG. It is mandatory to follow adequate clinical research methodology in executing and reporting such studies.

Objective: To summarize the evidence from epidemiological studies examining the association between Helicobacter pylori infection and hyperemesis gravidarum., Design: Systematic review and meta-analysis of case-control studies., Material and Methods: We searched the Medline/PubMed, Embase, Cinahl, ISI Web of Science and Biological Abstracts databases from 1966 to 17 June 2008 and finally Google Scholar. A total of 25 case-control studies were identified. Both fixed-effect and random-effect models were used to synthesize the results of individual studies. The Cochran Q, tau(2) of between-study variance and index of heterogeneity (I(2)) were used to evaluate heterogeneity. Heterogeneity between studies was examined by subgroup and random effect meta-regression analyses. Publication bias was evaluated., Results: Publication bias was not observed. The random model pooled estimate was odds ratio = 3.32, 95 % confidence interval (CI): 2.25-4.90. A high heterogeneity was pinpointed (I(2) = 80 %, 95 % CI: 65-89). Subgroup analysis and meta-regression showed a weaker association in studies with a clear definition of hyperemesis gravidarum compared to studies without this condition, and weaker association in recent studies compared to earlier studies. Meta-regression showed that these two study characteristics explained 40% of heterogeneity between studies., Conclusions: Exposure to H. pylori appears to be associated with an increased risk of hyperemesis gravidarum. The residual heterogeneity might have different reasons. Given the high prevalence of H. pylori, the public health consequence of H. pylori with regard to hyperemesis gravidarum may be important.

Background: The etiology of Hyperemesis gravidarum (HG) is unclear. To test the hypothesis of an association between Helicobacter pylori infection and HG, an institution-based case-control study was performed at Aker University Hospital (AUH) during 1994-1999., Material and Method: From the same source population, 244 incident cases of HG and 244 pregnant women free of the disease (controls) were consecutively identified., Results: H. pylori were noted in 105 cases and 58 control subjects. The presence of H. pylori increased the risk of HG more than two fold (OR = 2.42, 95% CI: 1.64-3.57, P < 0.001). This association was much stronger in Africans as compared to non-Africans (OR = 5.26, 95% CI: 1.04-26.57 vs. OR = 1.67, 95% CI: 1.07-2.61) after controlling for the confounding effect of maternal age. A gradient effect of exposure to H. pylori, determined by presence of specific IgG antibody in serum, and increased frequency of HG was present in Africans (test for linear trend P = 0.05) and non-Africans (test for linear trend P = 0.004)., Conclusion: These results indicate that H. pylori increase the risk of HG with a dose-response pattern and stronger in Africans.