Effect of statins on the development of renal dysfunction

Hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) decrease serum cholesterol. Dyslipidemia is believed to be associated with the development of renal dysfunction. It was postulated that statins may reduce the development of renal dysfunction. The effect of statin use on the development of renal dysfunction in 197,551 patients (Department of Veterans Affairs, Veterans Integrated Service Network 16 [VISN16] database) was examined. Of these patients, 29.5% (58,332 patients) were statin users and 70.5% (139,219 patients) were not. Development of renal dysfunction was defined as doubling of baseline creatinine or increase in serum creatinine > or =0.5 mg/dl from the first to last measurement with a minimum of 90 days in between. During 3.1 years of follow-up, 3.4% of patients developed renal dysfunction. After adjustment for demographics, diabetes mellitus, smoking, hypertension, and other medications (mainly angiotensin-converting enzyme inhibitors, calcium channel blockers, and aspirin), use of statins decreased the odds of developing renal dysfunction by 13% (odds ratio [OR] 0.87, 95% confidence interval [CI] 0.82 to 0.92, p <0.0001). The beneficial effect of statins appeared to be independent of the decrease in cholesterol. Other variables that affected the development of renal dysfunction were age (OR 1.04, 95% CI 1.03 to 1.04, p <0.0001), diabetes (OR 1.77, 95% CI 1.68 to 1.86, p <0.0001), hypertension (OR 1.11, 95% CI 1.02 to 1.2, p = 0.0153), and smoking (OR 1.12, 95% CI 1.02 to 1.24, p = 0.0244). In conclusion, statin use may retard the development of renal dysfunction. The beneficial effect of statins in preventing the development of renal dysfunction appears to be independent of their lipid-lowering effect.     

Continuous monitoring of mixed venous oxygen saturation in patients with acute myocardial infarction

Continuous measurement of mixed venous oxygen saturation (SvO2) has been suggested as an adjunct in monitoring critically ill patients. We evaluated SvO2 monitoring in 24 patients suffering from complicated myocardial infarctions. Cardiac output and arterial lactate levels were measured when there were persistent 5 percent changes in SvO2, and otherwise, every 12 hours or as indicated clinically. Increases in SvO2 by 5 and 10 percent corresponded with an increase in cardiac index in 78.5 percent and 75 percent of measurements, respectively. Decreases in SvO2 by 5 and 10 percent corresponded with decreases in cardiac index in 45.5 percent and 61 percent of measurements. Twenty percent changes in cardiac index showed dissimilar directional changes with SvO2 in 62 percent of cases. Arterial blood lactate levels correlated poorly with SvO2. Survivors had significantly higher mean SvO2 and cardiac indices than nonsurvivors (p less than 0.01). The clinical management of patients with myocardial infarction may not be altered in view of the limitations of SvO2 in reflecting tissue hypoxia. We conclude that continuous monitoring of SvO2 may not be a sensitive measure of cardiac output after acute myocardial infarction.     

High molecular weight kininogen inhibits thrombin-induced platelet aggregation and cleavage of aggregin by inhibiting binding of thrombin to platelets.

In this study we show that high molecular weight kininogen (HK) inhibited alpha-thrombin-induced aggregation of human platelets in a dose-dependent manner with complete inhibition occurring at plasma concentration (0.67 mumol/L) of HK. HK (0.67 mumol/L) also completely inhibited thrombin-induced cleavage of aggregin (Mr = 100 Kd), a surface membrane protein that mediates adenosine diphosphate (ADP)-induced shape change, aggregation, and fibrinogen binding. The inhibition of HK was specific for alpha- and gamma-thrombin-induced platelet aggregation, because HK did not inhibit platelet aggregation induced by ADP, collagen, calcium ionophore (A23187), phorbol myristate acetate (PMA), PMA + A23187, or 9,11-methano derivative of prostaglandin H2 (U46619). These effects were explained by the ability of HK, at physiologic concentration, to completely inhibit binding of 125I-alpha-thrombin to washed platelets. As a result of this action of HK, this plasma protein also completely inhibited thrombin-induced secretion of adenosine triphosphate, blocked intracellular rise in Ca2+ in platelets exposed to alpha- and gamma-thrombin, inhibited thrombin-induced platelet shape change, and blocked the ability of thrombin to antagonize the increase in intracellular cyclic adenosine monophosphate (cAMP) levels induced by iloprost. Because elevation of cAMP is known to inhibit binding of thrombin to platelets, we established that HK did not increase the intracellular concentration of platelet cAMP. Finally, HK did not inhibit enzymatic activity of thrombin. To study the role of HK in the plasma environment, we used gamma-thrombin to avoid fibrin formation by alpha-thrombin. Platelet aggregation induced by gamma-thrombin was also inhibited by HK in a dose-dependent manner. The EC50 (concentration to produce 50% of the maximum rate of aggregation) of gamma-thrombin for washed platelets was 7 nmol/L and increased to 102 nmol/L when platelets were suspended in normal human plasma. The EC50 for platelet aggregation induced by alpha-thrombin in plasma deficient in total kininogen was 40 nmol/L. When supplemented with HK at plasma concentration (0.67 mumol/L), the EC50 increased to 90 nmol/L, a value similar to that for normal human plasma. These results indicate that (1) HK inhibits thrombin-induced platelet aggregation and cleavage of aggregin by inhibiting binding of thrombin to platelets; (2) HK is a specific inhibitor of platelet aggregation induced by alpha- and gamma-thrombin; and (3) HK plays a role in modulating platelet aggregation stimulated by alpha-thrombin in plasma.     

More Money,Fewer Lives: The Cost Effectiveness of Welfare Reform in the United States

Objectives. We evaluated the economic benefits of Temporary Assistance to Needy Families (TANF) relative to the previous program, Aid to Families with Dependent Children (AFDC).Methods. We used pooled mortality hazard ratios from 2 randomized controlled trials—Connecticut Jobs First and the Florida Transition Program, which had follow-up from the early and mid-1990s through December 2011—and previous estimates of health and economic benefits of TANF and AFDC. We entered them into a Markov model to evaluate TANF’s economic benefits relative to AFDC and weigh them against the potential health threats of TANF.Results. Over the working life of the average cash assistance recipient, AFDC would cost approximately $28 000 more than TANF from the societal perspective. However, it would also bring 0.44 additional years of life. The incremental cost effectiveness of AFDC would be approximately $64 000 per life-year saved relative to TANF.Conclusions. AFDC may provide more value as a health investment than TANF. Additional attention given to the neediest US families denied cash assistance could improve the value of TANF.Aid to Families with Dependent Children (AFDC) was the primary cash assistance program in the United States until 1996.1 In that program, participants could receive cash assistance indefinitely. However, some policymakers questioned the logic of paying able-bodied citizens indefinitely because welfare might serve as an incentive to stay out of the workforce. These concerns were heard, and a number of randomized controlled trials were conducted in multiple states to test the effect of time limits for welfare benefits.2These randomized controlled trials found not only that time limits to cash assistance incentivized participants to move into the workforce, but also that they produced increases in earnings relative to traditional AFDC.2,3 Ultimately, these experiments contributed to the passage of the Personal Responsibility and Work Opportunity Reconciliation Act in 1996.1 This act was perhaps one of the most sweeping US policies enacted within the past 2 decades and one of the few large-scale policies to be passed on the basis of a large and convincing body of scientific evidence.1,4This act ended the federal guarantee of income support to poor families, replacing AFDC with a program called Temporary Assistance to Needy Families (TANF). Under TANF, states were given block grants along with relative autonomy over many aspects of welfare policy. Thus, TANF was implemented differently in different states, with some states offering much more generous benefits than others.5 The time limits in TANF were accompanied by incentives for work, such as earnings disregards (allowing recipients to remain on welfare even while earning money) and, in some instances, job training. As a result of TANF, welfare rolls have plummeted, saving taxpayer money and increasing family earnings.6However, despite these net benefits, both the early randomized controlled trials and later studies of the real-world impacts of TANF showed that some participants—almost all of whom were single women with children—were simply unable to get jobs.2,7 Risk factors for unemployment after the expiration of time limits may have included large family size, the presence of young children at home, or mothers who have a mental or physical disability.5,8–10 Those who could not garner employment after their time limits expired often had to rely on friends and family for survival.2,7,9,10Moreover, the earlier trials that uncovered these problems almost always coupled time limits with extensive benefits (such as child care) that are not provided under TANF in the vast majority of states today. As welfare rolls declined, states tended to spend the extra funds left over in their federal block grants on other, often unrelated programs.7 Therefore, one might expect more adverse outcomes in the real-world implementation of TANF than in the early randomized controlled trials. Fortunately, because states implemented TANF in different ways, these impacts were possible to study in a quasi-experimental manner. Studies exploiting spatiotemporal variations in implementation of time limits in the real world have shown similar benefits to the earlier randomized controlled trials,2,6,11,12 but also similar harms.7,10,13Specifically, TANF enrollees with preschool-aged children or larger families are both more likely to be food insecure and, at least among those required to enter the workforce quickly, in poorer mental health.7,9,10,14 Spatiotemporal analyses have suggested that time limits imposed under TANF were also associated with an overall increase in infant mortality.13 Long-term follow-up data from one such trial, Connecticut Jobs First (CJF), subsequently showed that treatment produced a nonsignificant 13% increase in mortality among all recipients and a nonsignificant 54% increase in mortality among women with more than 2 children.15 In the Florida Transition Program (FTP), treatment with time limits produced a 16% increase in mortality hazards.16 Whether this increase was statistically significant depended on the model specification. Taken together, these data suggest that women with smaller families and who are able bodied are better off under TANF than AFDC. However, women who cannot work because of disability or family obligations may have been better off with respect to health and longevity under AFDC than TANF. This hypothesis is supported by evidence that many women shifted from TANF to Supplemental Security Income, the program responsible for providing disability payments.17Despite its overall benefits, TANF is a program for which the nonpartisan US Government Accountability Office has pointed out that reform is needed, particularly with respect to provisions for those who are unable to work (e.g., because of caregiving responsibilities or poor mental or physical health).7 Although many experts have felt that TANF has been a success when evaluated on the basis of mean monetary and social impacts, we asked whether TANF retains its value when adverse health impacts are assessed.     

How to define pathologic pelvic floor descent in MR defecography during defecation?

Abdominal Radiology - To assess the extents of pelvic floor descent both during the maximal straining phase and the defecation phase in healthy volunteers and in patients with pelvic floor...