2 Minute Medicine Rewind August 23 – August 30, 2015
Perioperative Bridging Anticoagulation in Patients with Atrial Fibrillation
Anticoagulation with warfarin for stroke prevention in atrial fibrillation must be interrupted in patients who undergo elective operations. The need to bridge anticoagulation during the perioperative period is uncertain. In this international multicenter study, the authors performed a randomized, double-blind, placebo-controlled trial in which after perioperative interruption of warfarin therapy patients were randomly assigned to receive bridging anticoagulation therapy with low-molecular-weight heparin or matching placebo administered subcutaneously twice daily, from 3 days before the procedure until 24 hours before the procedure and then for 5 to 10 days after the procedure. The authors hypothesized that forgoing bridging anticoagulation would be noninferior to bridging with low molecular weight heparin for the prevention of perioperative arterial thromboembolism and would be superior to bridging with respect to major bleeding. The authors found the incidence of arterial thromboembolism was 0.4% in the non-bridging group and 0.3% in the bridging group (95% CI, −0.6 to 0.8; P = 0.01 for noninferiority). The incidence of major bleeding was 1.3% in the no-bridging group and 3.2% in the bridging group (relative risk, 0.41; 95% CI, 0.20 to 0.78; P = 0.005 for superiority). Therefore the authors concluded that in the perioperative period for patients on warfarin, forgoing bridging anticoagulation was noninferior to perioperative bridging with low-molecular-weight heparin for the prevention of arterial thromboembolism and decreased the risk of major bleeding.
Lack of high quality evidence currently exists regarding obstetrical outcomes between family physicians and obstetricians. For example, none of the published studies have adjusted for unmeasured factors that might affect a mothers choice of delivery provider and the outcomes that result. The authors of this study aimed to address these issues by performing a retrospective population-based cohort study of all Canadian hospital births between 2006 and 2009 to compare perinatal mortality and maternal morbidity and mortality for deliveries by family physicians and obstetricians using instrumental variable methodology. The authors found that there were 3600 perinatal deaths and 14 394 cases of maternal morbidity among 799 823 infants and 793 053 mothers at 390 hospitals. Comparing family physicians to obstetricians, the relative risk of perinatal mortality was 0.98 (95% CI 0.85–1.14) and of maternal morbidity was 0.81 (95% CI 0.70–0.94) according to logistic regression. The respective relative risks were 0.97 (95% CI 0.58–1.64) and 1.13 (95% CI 0.65–1.95) according to instrumental variable methods. Therefore, there was a similar risk of perinatal mortality and adverse maternal outcomes when comparing the two different physicians. However, further research needs to investigate whether there are differences between these groups in terms of other perinatal outcomes.
Shared Predisposition in the Association Between Cannabis Use and Subcortical Brain Structure
Cannabis use has been linked to alterations in brain structure of developing youth. The purpose of this study was to examine whether cannabis exposure, age at onset of use, and lifetime frequency of use were associated with whole-brain volume, amygdala, hippocampus, ventral striatal or orbitofrontal cortex volumes. The second objective was to quantify the degree to which shared genetic and individual specific environmental factors contributed to these associations. In this study, authors conducted a cross-sectional diagnostic interview, behavioral and neuroimaging study from 2012 to 2014 with 262 participants to investigate the abovementioned questions. The authors found that despite cannabis exposure being related to a smaller left amygdala (approximately 2.3%; P = .007) and right ventral striatum volumes (approximately 3.5%; P < .005), these volumetric differences were within the range of normal variation. The association between left amygdala volume and cannabis use was largely owing to shared genetic factors (ρ = −0.43; P = .004). Importantly, brain volumes did not differ between sex-matched siblings. Both the exposed and unexposed siblings in pairs discordant for cannabis exposure showed reduced amygdala volumes relative to members of concordant unexposed pairs (fixed effect = 12.56; t = 2.97; P = .003). These results provide evidence that the observed cannabis- related volumetric differences were well within the range of normal variation. When using a simple index of exposure (ie, ever vs never use), the authors found no evidence for the causal influence of cannabis exposure on amygdala volume.
Temporal course and pathologic basis of unawareness of memory loss in dementia
It remains uncertain how common unawareness of memory impairment is in persons with dementia, its timing of onset, or why some are apparently affected more than others. The purpose of this study was to characterize the natural history and neuropathologic basis of unawareness of memory loss in late-life dementia. The authors used three longitudinal clinical-pathologic cohort studies with 2,092 elderly patients who had no memory or cognitive impairment at baseline. Annual evaluations included clinical classification of dementia plus self-rating and performance testing of memory. At death, there was a uniform neuropathologic examination to quantify 7 dementia-related pathologies. The authors found that memory ratings were modestly correlated with memory performance. In a subset of 239 persons who developed dementia, episodic memory awareness was stable until a mean of 2.6 years before dementia onset (95% CI 22.7, –1.6) after which memory awareness declined rapidly (mean annual change 20.32, 95% CI –0.37, –0.28). In addition, older age at baseline was associated with later onset of memory unawareness. Neuropathology at death showed transactive response DNA-binding protein 43 (TDP-43) pathology, tau tangles, and gross cerebral infarcts were related to decline in memory awareness. The results suggest that declining awareness of memory impairment occurs approximately 2-3 years before the onset of dementia and is an essentially inevitable manifestation of late-life dementia.
Smoking cessation is a major target for diabetes management. Important to quantify is the excess mortality and morbidity risks associated with smoking. The authors performed a systematic review and meta-analysis of prospective cohort studies to evaluate the relation of active smoking with risk of total mortality and cardiovascular events among diabetic patients. A total of 89 cohort studies were included in the systematic review. For total mortality, the pooled adjusted RR associated with smoking was 1.55 (95% CI 1.46-1.64) for total mortality (48 studies with 1,132,700 participants and 109,966 deaths). For cardiovascular mortality the pooled adjusted RR was 1.49 (CI 1.29-1.71) (13 studies with 37,550 participants and 3,163 deaths). Compared to non-smokers, former smokers were at a moderately elevated risk of total mortality (1.19; 1.11-1.28), cardiovascular mortality (1.15; 1.00-1.32), cardiovascular disease (1.09; 1.05-1.13) and coronary heart disease (1.14; 1.00-1.30), but not for stroke (1.04; 0.87-1.23). These results provide evidence that active smoking is a significant modifiable factor for adverse health consequences in diabetic patients. In addition, smoking cessation was associated with reduced risks compared to active smoking.
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