Glyceryl trinitrate (GTN), also known as nitroglycerin, has been used to treat angina and heart failure for more than 130 years. Recently, it was shown that mitochondrial aldehyde dehydrogenase-2 (ALDH2) is responsible for formation of NO, the metabolite needed for GTN efficacy. In the present study, we show that the common G-to-A polymorphism in exon 12 of ALDH2 -resulting in a Glu504Lys replacement that virtually eliminates ALDH2 activity in both heterozygotes and homozygotes -is associated with a lack of efficacy of sublingual GTN in Chinese subjects. We also show that the catalytic efficiency (V max /K m ) of GTN metabolism of the Glu504 protein is approximately 10-fold higher than that of the Lys504 enzyme. We conclude that the presence of the Lys504 allele contributes in large part to the lack of an efficacious clinical response to nitroglycerin; we recommend that this genetic factor be considered when administering nitroglycerin to patients, especially Asians, 30-50% of whom possess the inactive ALDH2*2 mutant allele.
OBJECTIVEHypoglycemia is associated with failure to show cardiovascular benefit and increased mortality of intensive glycemic control in randomized clinical trials. This retrospective cohort study aimed to examine the impact of hypoglycemia on vascular events in clinical practice.RESEARCH DESIGN AND METHODSPatients with type 2 diabetes were identified by ICD-9-CM codes (250.xx except for 250.x1 and 250.x3) between 1 January 2004 and 1 September 2010 from the Veterans Integrated Service Network 16. Index date was defined as the first date of new antihyperglycemic medications (index treatment). Patients with 1-year preindex records of hypoglycemia, cardiovascular, and microvascular diseases were excluded. The hypoglycemia group was identified by ICD-9-CM codes (250.8, 251.0, 251.1, and 251.2) within the index treatment period. A propensity score–matched group was used as control subjects. Cardiovascular events, microvascular complications, and all-cause death were compared using Kaplan-Meier analysis and Cox proportional hazards regression model.RESULTSAmong the unmatched sample (N = 44,261), the hypoglycemia incidence rate was 3.57/100 patient-years. The matched sample (hypoglycemia group: n = 761; control group: n = 761) had a median follow-up of 3.93 years, mean age of 62.6 ± 11.0 years, and preindex HbA1c of 10.69 ± 2.61%. The 1-year change in HbA1c was similar (hypoglycemia group −0.51 vs. control group −0.32%, P = 0.7244). The hypoglycemia group had significantly higher risks of cardiovascular events (hazard ratio 2.00 [95% CI 1.63–2.44]) and microvascular complications (1.76 [1.46–2.11]) but no statistical mortality difference. Patients with at least two hypoglycemic episodes were at higher risks of vascular events than those with one episode (1.53 [1.10–1.66]).CONCLUSIONSHypoglycemia is associated with higher risks of incident vascular events. Patients with hypoglycemia should be monitored closely for vascular events.
Aim: To systematically evaluate the effect of working environment on implicit rationing of nursing care. Background: Research has established direct and indirect associations between work environment and adverse patient outcomes. However, the causal nature of this relationship is uncertain, and implicit rationing has been proposed as a mediating factor between the work environment and patient outcomes. Method: Eight databases were searched for articles published between May 2000 and May 2019. Results: The reviewed articles provided evidence for the negative correlation between working environment and implicit rationing in 15 studies, and one of the studies showed that the correlation was not strong. There were differences in the levels of implicit rationing in different hospitals, units and shifts. Conclusion: The degree of influence of various factors in the working environment on implicit rationing is different. In addition, the working environment is only one of the factors that affects implicit rationing. Implications for Nursing Management: Nursing managers initiatives to improve nurses' work environments should include improve nurses' perception of the adequacy of staffing and resources and improving teamwork to decrease nursing care left undone, so as to improve nurse outcomes and quality of care.
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