***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: This pilot aims to better underst and the market for childcare in Saudi Arabia – both the supply and dem and sides – and to design a r and omized controlled experiment to test whether access to affordable day care ( in the form of subsidies , for example ) would incentivize Saudi mothers to search actively for employment and to remain employed once they are hired . In addition , the study seeks to underst and the degree to which employment early on in one ’s life impacts employment in later stages . The pilot will provide information on the groups of women the experiment should target , appropriate levels for the childcare subsidy , and the quality and current geographic locations of daycare sites . Expected Impact Determine the effects of facilitating childcare access on Saudi women ’s employment . PRINCIPAL INVESTIGATORS  Boston University Patricia Cortes  Harvard University Claudia Goldin  Swarthmore College Jennifer The high prevalence of hypercholesterolemia in kidney transplant recipients probably contributes to the high cardiovascular mortality in these patients . Except for diet , there is no generally recommended cholesterol-lowering treatment . We conducted a double-blind , r and omized , placebo-controlled study with low-dose simvastatin in 40 ciclosporin (CS)-treated kidney transplant recipients during 16 weeks , focusing on side effects and dose finding . In the simvastatin group , the mean serum total and LDL cholesterol concentrations decreased by 23 and 33 % , respectively , and the mean serum HDL cholesterol concentration increased by 12 % , after 4 weeks of treatment with simvastatin 10 mg daily . Increasing the dose to 20 mg daily in a few patients only result ed in marginal further reductions of the serum cholesterol concentrations at the expense of doubling the plasma simvastatin 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitory activity concentrations . The differences between the changes in the serum cholesterol concentrations in the simvastatin group and the negligible changes in the placebo group were statistically significant . There was no case of proximal myopathy and the serum creatine kinase concentrations did not differ between treatment groups . In conclusion , low-dose simvastatin appears to be a well tolerated and efficacious cholesterol-lowering treatment in CS-treated kidney transplant recipients .  Simvastatin 10 mg daily seems to be the most suitable dose for the majority of these patients Purpose of review To review recent publications concerning the epidemiology and management of cardiovascular disease in the stages of chronic kidney disease . Recent findings Chronic kidney disease is a state of increased risk for atherosclerotic and cardiomyopathic disease . The mechanisms of cardiovascular disease probably change with the different stages of chronic kidney disease . Both proteinuria and decreased glomerular filtration rate are probably independent cardiovascular disease risk factors , although the impact of the latter is modest . Traditional risk factors are important predictors of cardiovascular disease in chronic kidney disease . Recent r and omized controlled trials and cohort studies have supported interventions for smoking cessation , blood pressure control , renin – angiotensin system blockade , the correction of lipid abnormalities , and utilizing antiplatelet agents . Some uraemia-related risk factors predict the development of cardiovascular disease , particularly hypoalbuminaemia , inflammation , anaemia , and homocysteinaemia . However , r and omized controlled trials of anaemia correction and of an increased quantity of dialysis were negative . Summary The role of oxidant stress , divalent ion abnormalities , various lipid abnormalities and other potential factors require further investigation . To determine whether these uraemia-related factors are markers of cardiovascular disease risk or are actually cardiotoxic requires additional r and omized controlled trials The incidence of cardiovascular disease ( CVD ) is very high in patients with chronic kidney ( CKD ) disease and in kidney transplant recipients . Indeed , available evidence for these patients suggests that the 10‐year cumulative risk of coronary heart disease is at least 20 % , or roughly equivalent to the risk seen in patients with previous CVD . Recently , the National Kidney Foundation 's Kidney Disease Outcomes Quality Initiative ( K/DOQI ) published guidelines for the diagnosis and treatment of dyslipidemias in patients with CKD , including transplant patients . It was the conclusion of this Work Group that the National Cholesterol Education Program Guidelines are generally applicable to patients with CKD , but that there are significant differences in the approach and treatment of dyslipidemias in patients with CKD compared with the general population . In the present document we present the guidelines generated by this workgroup as they apply to kidney transplant recipients . Evidence from the general population indicates that treatment of dyslipidemias reduces CVD , and evidence in kidney transplant patients suggests that judicious treatment can be safe and effective in improving dyslipidemias . Dyslipidemias are very common in CKD and in transplant patients . However , until recently there have been no adequately powered , r and omized , controlled trials examining the effects of dyslipidemia treatment on CVD in patients with CKD . Since completion of the K/DOQI guidelines on dyslipidemia in CKD , the results of the Assessment of Lescol in Renal Transplantation ( ALERT ) Study have been presented and published . Based on information from r and omized trials conducted in the general population and the single study conducted in kidney transplant patients , these guidelines , which are a modified version of the K/DOQI dyslipidemia guidelines , were developed to aid clinicians in the management of dyslipidemias in kidney transplant patients . These guidelines are divided into four sections . The first section ( Introduction ) provides the rationale for the guidelines , and describes the target population , scope , intended users , and methods . The second section presents guidelines on the assessment of dyslipidemias  ( guidelines 1–3 ) , while the third section offers guidelines for the treatment of dyslipidemias  ( guidelines 4–5 ) . The key guideline statements are supported mainly by data from studies in the general population , but there is an urgent need for additional studies in CKD and in transplant patients . Therefore , the last section outlines recommendations for research BACKGROUND Renal transplant recipients are at increased risk of premature cardiovascular disease . Although statins reduce cardiovascular risk in the general population , their efficacy and safety in renal transplant recipients have not been established . We investigated the effects of fluvastatin on cardiac and renal endpoints in this population . METHODS We did a multicentre , r and omised , double-blind , placebo-controlled trial in 2102 renal transplant recipients with total cholesterol 4.0 - 9.0 mmol/L. We r and omly assigned patients fluvastatin ( n=1050 ) or placebo ( n=1052 ) and follow up was for 5 - 6 years . The primary endpoint was the occurrence of a major adverse cardiac event , defined as cardiac death , non-fatal myocardial infa rct ion ( MI ) , or coronary intervention procedure . Secondary endpoints were individual cardiac events , combined cardiac death or non-fatal MI , cerebrovascular events , non-cardiovascular death , all-cause mortality , and graft loss or doubling of serum creatinine . Analysis was by intention to treat . FINDINGS After a mean follow-up of 5.1 years , fluvastatin lowered LDL cholesterol concentrations by 32 % . Risk reduction with fluvastatin for the primary endpoint ( risk ratio 0.83 [ 95 % CI 0.64 - 1.06 ] , p=0.139 ) was not significant , although there were fewer cardiac deaths or non-fatal MI ( 70 vs 104 , 0.65 [ 0.48 - 0.88 ] p=0.005 ) in the fluvastatin group than in the placebo group . Coronary intervention procedures and other secondary endpoints did not differ significantly between groups . INTERPRETATION Although cardiac deaths and non-fatal MI seemed to be reduced , fluvastatin did not generally reduce rates of coronary intervention procedures or mortality . Overall effects of fluvastatin were similar to those of statins in other population During the last decades , transplantation has become an established tool for the treatment of terminal organ failure . Beside immunological factors , hyperlipidemia is the main problem after heart transplantation  , causing rapid transplant coronary artery disease ( TxCAD ) and poor long-term prognosis at the beginning of the transplantation . Heart transplant recipients are now effectively treated with lipid lowering substances , of which HMG-CoA-reductase inhibitors are the most potent . However , treatment with these substances correlates with an increased risk for the development of rhabdomyolysis due to therapy with the immunosuppressive cyclosporine A. Our study monitored the safety and efficacy of treatment with the HMG-CoA reductase inhibitor fluvastatin in heart transplant recipients compared to healthy controls . We investigated 10 patients receiving immunosuppressive therapy consisting of cyclosporine A , prednisone , and azathioprine who had increased concentrations of LDL-cholesterol ( LDL-C ) , and 10 age-matched healthy controls . The patients were treated with 40 mg/day fluvastatin for 4 weeks and 20 mg/day for 4 additional weeks . Control individuals received 40 mg/day fluvastatin for 4 weeks only . Parameters of  fluvastatin pharmacokinetics ( maximum concentration of the drug ( Cax , ) , time ( tmax ) to reach Cmax , area under the concentration vs. time curve ( AUCOh 24h ) , elimination halflife time ( t,2 ) ) , apparent total body clearance ( CL ) , blood cyclosporine A concentration , plasma lipids , and safety parameters were determined in both study groups at the beginning of the study and after 4 weeks . The latter were determined in the patient group also after 8 and 12 weeks . Treatment with 40 mg/day fluvastatin caused a significant decrease in total cholesterol ( patients : 5.47 ± 1.32 mmol/L vs. 7.30 ± 1.83 mmol/L ; controls : 4.69 ± 0.64 mmolIL vs. 5.81 ± 0.72 mmol/L ) , LDL-C ( patients : 3.28 + 1.25 mmol/L vs. 5.00 ± 1.85 mmol/L ; controls : 2.58 ± 0.63 mmol/L vs. 3.50 ± 0.70 mmolJL ) , and triglycerides ( patients : 1.99 ± 0.77 mmol/L vs. 2.50 ± 1.00 mmol/L ; controls : 1.24 ± 0.46 mmolIL vs. 1.72 ± 0.67 mmol/L ) in both study groups , whereas HDL-C was not significantly changed ( patients : 1.29 ± 0.35 mmol/L vs. 1.17 ± 0.32 mmol/L ; controls : 1.55 ± 0.30 mmol/L vs. 1.53 ± 0.26 mmol/L ) . Values of C,,m , and AUCOh 24h were higher in the patient group than in the control group ( day 1 , patients vs. controls , Cma , : 869.4 ± 604.0 ng/mL vs. 211.9 ± 113.9 ng/mL ; AUCOh24h : 1948.8 ± 1347.9 ng/mL*h vs. 549.4 ± 247.4 ng/mLh ) , whereas the corresponding value of CL was lower in the patient group ( 33.3 ± 24.5 L/h vs. 107.9 ± 95.8 L/h ) , and the values of t , , , . and t,2 showed no differences . In addition , values of C,,m , and AUCOb 24h after administration of 40 mg/day fluvastatin for 4 weeks in both groups were slightly higher than at the beginning , whereas the value of CL was slightly lower ( day 28 , patients vs. controls , C,,a , : 1530.4 ± 960.4 ng/mL vs. 254.7 ± 199.8 ng/mL ; AUCOb-240 : 2615.3 ± 1379.4 ng/mL*h vs. 841.8 ± 421.4 ng/mL*h ; CL : day 28 , 21.4 ± 15.3 L/h vs. 61.5 ± 36.6 L/h ) . Except for an intermittent increase of creatine kinase , safety parameters showed no increases within the observation period . Our data suggest that fluvastatin  effectively lowers plasma concentrations of cholesterol and LDL-C in patients after heart transplantation , however , the metabolism of fluvastatin is affected by concomitant therapy with cyclosporine A.  Serum concentrations  of fluvastatin should be monitored in cases of concomitant therapy with other substances interfering in the metabolism by competing cytochrome enzymes BACKGROUND Patients with chronic kidney disease are at increased risk for cardiovascular disease , but the efficacy and safety of simvastatin and aspirin are unknown in this patient group . METHODS Patients were r and omly assigned in a 2 x 2 factorial design to the 
    Output:
    
The Assessment of Lescol in Renal Transplant trial , the largest trial so far , suggested that dyslipidemia management with statins in RTRs is associated with a significant reduction in the incidence of cardiac death and nonfatal myocardial infa rct ion ( although differences in the combined primary end point were not statistically significant ) .