Editor's Choice - Effect of Statins on Total Mortality in Abdominal Aortic Aneurysm Repair: A Systematic Review and Meta-analysis.

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 (I2 = 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.

Long-term effects (> 24 months) of multiple lifestyle intervention on major cardiovascular risk factors among high-risk subjects: a meta-analysis.

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 (I2 = 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 (I2 = 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.

Falls in hospital: a case-control study.

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.

Khat chewing increases the risk for developing chronic liver disease: A hospital-based case-control study.

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).

Mediastinitis in open heart surgery: a systematic review and meta-analysis of risk factors.

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.

Risk factors for severe postpartum hemorrhage: a case-control study.

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.

Perioperative humoral stress response to laparoscopic versus open aortobifemoral bypass surgery.

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.

Pregnancy outcomes following maternal kidney transplantation: a national cohort study.

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.

Aetiology and diagnostics of paediatric hydrocephalus across Africa: a systematic review and meta-analysis.

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.

Randomized trial of cardiovascular prevention in Norway combining an in-hospital lifestyle course with primary care follow-up: the Hjerteløftet study.

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).

Critical appraisal of case-control studies of risk factors or etiology of Hyperemesis gravidarum.

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.

Remote Ischemic Conditioning in Patients with Acute Coronary Syndromes: A Systematic Review with Meta-Analysis and Trial Sequential Analysis.

OBJECTIVE: 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.

Helicobacter pylori infection and hyperemesis gravidarum: a systematic review and meta-analysis of case-control 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.

Effect of oral ß-blocker treatment on mortality in contemporary post-myocardial infarction patients: a systematic review and meta-analysis.

Aims: Guidelines concerning ß-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 ß-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 ß-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 ß-blockers and all-cause mortality. A possible beneficial effect in AMI survivors needs to be tested by large randomized clinical trials.

Thirty-day readmissions in surgical and transcatheter aortic valve replacement: A systematic review and meta-analysis.

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.

Atrial fibrillation and the risk for myocardial infarction, all-cause mortality and heart failure: A systematic review and meta-analysis.

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.

Prolonging the duration of single-shot intrathecal labour analgesia with morphine: A systematic review.

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 (I2=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.

Comparison of the acute-phase response after laparoscopic versus open aortobifemoral bypass surgery: a substudy of a randomized controlled trial.

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.

Thromboprophylaxis with low molecular weight heparin versus unfractionated heparin in intensive care patients: a systematic review with meta-analysis and trial sequential analysis.

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.

Toxoplasma prevalence among pregnant women in Norway: a cross-sectional study.

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.