Warfarin anticoagulation and outcomes in patients with atrial fibrillation: a systematic review and metaanalysis

OBJECTIVE: To examine the relationship between international normalized ratio (INR) and outcomes (major bleeding events and strokes) in patients with atrial fibrillation (AF) receiving anticoagulation with warfarin. METHODS: A systematic review and metaanalysis of studies published in the English language between January 1, 1985, and October 30, 2002, was performed. MEDLINE (PubMed), Current Contents, and relevant reference lists were searched. Studies enrolling patients with nonvalvular AF receiving warfarin anticoagulation were eligible for inclusion if they reported stroke and/or major bleeding events in relation to INR, or time spent in therapeutic range. The risk of bleeds in overanticoagulated patients (INR > 3) and the risk of strokes in underanticoagulated patients (INR < 2) were assessed. RESULTS: Twenty-one studies (6,248 patients) met all inclusion criteria. Of the 21 studies, a target conventional INR of 2 to 3 was used in 9 studies. An INR < 2, compared with an INR > or = 2, was associated with an odds ratio (OR) for ischemic events of 5.07 (95% confidence interval [CI], 2.92 to 8.80). An INR > 3, compared with an INR < or = 3, was associated with an OR for bleeding events of 3.21 (95% CI, 1.24 to 8.28). On average, in the four studies with a target INR range of 2 to 3, patients with AF receiving warfarin spent 61% of time within, 13% of time above, and 26% below the therapeutic range. CONCLUSION: Available evidence indicates that in patients with nonvalvular AF, the risk of ischemic stroke with insufficient warfarin anticoagulation (INR < 2), and the risk of bleeding events with overanticoagulation (INR > 3) are significantly higher relative to patients with AF maintained within the recommended INR of 2 to 3. However, the published data are sparse, heterogeneous, and primarily reported from clinical trials. More studies evaluating clinical outcomes in relation to INR are needed, especially in a real-world setting.     

The Safety and Efficacy of Approaches to Liver Resection: A Meta-Analysis

Background:The aim of this study is to compare the safety and efficacy of conventional laparotomy with those of robotic and laparoscopic approaches to hepatectomy.Database:Independent reviewers conducted a systematic review of publications in PubMed and Embase, with searches limited to comparative articles of laparoscopic hepatectomy with either conventional or robotic liver approaches. Outcomes included total operative time, estimated blood loss, length of hospitalization, resection margins, postoperative complications, perioperative mortality rates, and cost measures. Outcome comparisons were calculated using random-effects models to pool estimates of mean net differences or of the relative risk between group outcomes. Forty-nine articles, representing 3702 patients, comprise this analysis: 1901 (51.35%) underwent a laparoscopic approach, 1741 (47.03%) underwent an open approach, and 60 (1.62%) underwent a robotic approach. There was no difference in total operative times, surgical margins, or perioperative mortality rates among groups. Across all outcome measures, laparoscopic and robotic approaches showed no difference. As compared with the minimally invasive groups, patients undergoing laparotomy had a greater estimated blood loss (pooled mean net change, 152.0 mL; 95% confidence interval, 103.3–200.8 mL), a longer length of hospital stay (pooled mean difference, 2.22 days; 95% confidence interval, 1.78–2.66 days), and a higher total complication rate (odds ratio, 0.5; 95% confidence interval, 0.42–0.57).Conclusion:Minimally invasive approaches to liver resection are as safe as conventional laparotomy, affording less estimated blood loss, shorter lengths of hospitalization, lower perioperative complication rates, and equitable oncologic integrity and postoperative mortality rates. There was no proven advantage of robotic approaches compared with laparoscopic approaches.     

Prähospitale Behandlung des akuten Koronarsyndroms unter DOAK-Dauertherapie

Die Anaesthesiologie - Trotz steigender Inzidenz von Patienten, die unter einer Dauertherapie mit einem direkten oralen Antikoagulans (DOAK) ein akutes Koronarsyndrom („acute coronary...     

Robotic Versus Laparoscopic Colorectal Surgery

Background:

Robotic approaches have become increasingly used for colorectal surgery. The aim of this study is to examine the safety and efficacy of robotic colorectal procedures in an adult population.

Study Design:

A systematic review of articles in both PubMed and Embase comparing laparoscopic and robotic colorectal procedures was performed. Clinical trials and observational studies in an adult population were included. Approaches were evaluated in terms of operative time, length of stay, estimated blood loss, number of lymph nodes harvested, and perioperative complications. Mean net differences and odds ratios were calculated to examine treatment effect of each group.

Results:

Two hundred eighteen articles were identified, and 17 met the inclusion criteria, representing 4,342 patients: 920 robotic and 3,422 in the laparoscopic group. Operative time for the robotic approach was 38.849 minutes longer (95% confidence interval: 17.944 to 59.755). The robotic group had lower estimated blood loss (14.17 mL; 95% confidence interval: –27.63 to –1.60), and patients were 1.78 times more likely to be converted to an open procedure (95% confidence interval: 1.24 to 2.55). There was no difference between groups with respect to number of lymph nodes harvested, length of stay, readmission rate, or perioperative complication rate.

Conclusions:

The robotic approach to colorectal surgery is as safe and efficacious as conventional laparoscopic surgery. However, it is associated with longer operative time and an increased rate of conversion to laparotomy. Further prospective randomized controlled trials are warranted to examine the cost-effectiveness of robotic colorectal surgery before it can be adopted as the new standard of care.     

Psychosocial group prevention and intervention programs for children and adolescents

Psychosocial group interventions provide a potent venue for promoting children's social competencies, self-regulation, and problem solving in a natural peer group context. Three exemplary prevention and intervention group programs were described that are empirically supported, theoretically rich, and flexible for application in residential care settings. Special considerations are offered for designing and implementing groups with this population.     

Factors influencing physicians' reported use of anticoagulation therapy in nonvalvular atrial fibrillation: a cross-sectional survey

BACKGROUND: Some elderly patients with nonvalvular atrial fibrillation (NVAF) who might benefit from warfarin therapy do not receive it. OBJECTIVE: The goal of this cross-sectional study was to identify physicians' attitudes and beliefs that are associated with their reported use of warfarin in case scenarios. METHODS: A self-administered survey was mailed to a cross-section of general internists randomly selected from a national pool of physicians in the American Medical Association Masterfile. Fourteen clinical vignettes were used, incorporating various comorbid conditions and risk factors for either major bleeding episode or embolic cerebrovascular accident (CVA). The outcome measure was the number of case vignettes for which warfarin was recommended. RESULTS: A total of 142 completed surveys (33% of 426 eligible respondents; 109 men, and 32 women [1 respondent did not provide gender]; mean [SD] age, 45 [10] years) were received. The median number of case vignettes for which warfarin was recommended was 10 (interquartile range, 8-12). We found no relationship between the perceived benefits of warfarin and its use in the case vignettes. However, the perceived risk for warfarin associated hemorrhage was strongly associated with reported warfarin use (P < 0.001). The physicians in our sample provided estimates of the annual rate of warfarin-associated intracerebral hemorrhage that were >10-fold higher than literature-based estimates, and physicians providing higher risk estimates tended to use warfarin less often. On multivariate logistic regression, physicians who recommended warfarin use in more vignettes were less likely to report anticipated regret of committing an error of omission (ischemic CVA in an untreated NVAF patient) (P < 0.001) or a loss-aversive risk preference (P = 0.027), and had a lower perceived annual risk for hemorrhage with warfarin (P < 0.001). Physician age, sex, primary mechanism of reimbursement, academic appointment, and the NVAF patient volume all were unrelated to warfarin use. CONCLUSIONS: Although the decision to use warfarin in NVAF was not driven by the perceived benefit, the perceived risks strongly affected warfarin use. Response bias is a potential limitation, but our data strongly suggest that physicians' attitudes toward anticipated regret and risk aversion can impact on their treatment recommendations.     

Chronic oesophageal stricture due to moniliasis.

A case of persistent oesophageal stricture due to moniliasis, which developed while the patient was symptomatic, is reported. The value and therapeutic implications of performing a repeat barium swallow even if the disease appears to be quiescent are discussed.     

Melatonin suppression of aerobic glycolysis (Warburg effect), survival signalling and metastasis in human leiomyosarcoma

Leiomyosarcoma (LMS) represents a highly malignant, rare soft tissue sarcoma with high rates of morbidity and mortality. Previously, we demonstrated that tissue‐isolated human LMS xenografts perfused in situ are highly sensitive to the direct anticancer effects of physiological nocturnal blood levels of melatonin which inhibited tumour cell proliferative activity, linoleic acid (LA) uptake and metabolism to 13‐hydroxyoctadecadienoic acid (13‐HODE). Here, we show the effects of low pharmacological blood concentrations of melatonin following oral ingestion of a melatonin supplement by healthy adult human female subjects on tumour proliferative activity, aerobic glycolysis (Warburg effect) and LA metabolic signalling in tissue‐isolated LMS xenografts perfused in situ with this blood. Melatonin markedly suppressed aerobic glycolysis and induced a complete inhibition of tumour LA uptake, 13‐HODE release, as well as significant reductions in tumour cAMP levels, DNA content and [³H]‐thymidine incorporation into DNA. Furthermore, melatonin completely suppressed the phospho‐activation of ERK 1/2, AKT, GSK3β and NF‐kB (p65). The addition of S20928, a nonselective melatonin antagonist, reversed these melatonin inhibitory effects. Moreover, in in vitro cell culture studies, physiological concentrations of melatonin repressed cell proliferation and cell invasion. These results demonstrate that nocturnal melatonin directly inhibited tumour growth and invasion of human LMS via suppression of the Warburg effect, LA uptake and other related signalling mechanisms. An understanding of these novel signalling pathway(s) and their association with aerobic glycolysis and LA metabolism in human LMS may lead to new circadian‐based therapies for the prevention and treatment of LMS and potentially other mesenchymally derived solid tumours.