Explore the vast range of titles available.

Statins lower high-sensitivity C-reactive protein (hsCRP) and cholesterol concentrations, and hypothesis generating analyses suggest that clinical outcomes improve in patients given statins who achieve hsCRP concentrations less than 2 mg/L in addition to LDL cholesterol less than 1·8 mmol/L (<70 mg/dL). However, the benefit of lowering both LDL cholesterol and hsCRP after the start of statin therapy is controversial. We prospectively tested this hypothesis. In an analysis of 15 548 initially healthy men and women participating in the JUPITER trial (87% of full cohort), we prospectively assessed the effects of rosuvastatin 20 mg versus placebo on rates of non-fatal myocardial infarction, non-fatal stroke, admission for unstable angina, arterial revascularisation, or cardiovascular death (prespecified endpoints) during a maximum follow-up of 5 years (median 1·9 years), according to on-treatment concentrations of LDL cholesterol (≥1·8 mmol/L or <1·8 mmol/L) and hsCRP (≥2 mg/L or <2 mg/L). We included all events occurring after randomisation. This trial is registered with ClinicalTrials.gov, number NCT00239681. Compared with placebo, participants allocated to rosuvastatin who achieved LDL cholesterol less than 1·8 mmol/L had a 55% reduction in vascular events (event rate 1·11 vs 0·51 per 100 person-years; hazard ratio [HR] 0·45, 95% CI 0·34–0·60, p<0·0001), and those achieving hsCRP less than 2 mg/L a 62% reduction (event rate 0·42 per 100 person-years; HR 0·38, 95% CI 0·26–0·56, p<0·0001). Although LDL cholesterol and hsCRP reductions were only weakly correlated in individual patients ( r values <0·15), we recorded a 65% reduction in vascular events in participants allocated to rosuvastatin who achieved both LDL cholesterol less than 1·8 mmol/L and hsCRP less than 2 mg/L (event rate 0·38 per 100 person-years; adjusted HR 0·35, 95% CI 0·23–0·54), versus a 33% reduction in those who achieved one or neither target (event rate 0·74 per 100 person-years; HR 0·67, 95% CI 0·52–0·87) (p across treatment groups <0·0001). In participants who achieved LDL cholesterol less than 1·8 mmol/L and hsCRP less than 1 mg/L, we noted a 79% reduction (event rate 0·24 per 100 person-years; HR 0·21, 95% CI 0·09–0·52). Achieved hsCRP concentrations were predictive of event rates irrespective of the lipid endpoint used, including the apolipoprotein B to apolipoprotein AI ratio. For people choosing to start pharmacological prophylaxis, reduction in both LDL cholesterol and hsCRP are indicators of successful treatment with rosuvastatin. AstraZeneca.

In the absence of vaccines or drugs, insecticides are the mainstay of Aedes-borne disease control. Their utility is challenged by the slow deployment of resources, poor community compliance and inadequate household coverage. Novel application methods are required. A 10% w/w metofluthrin \"emanator\" that passively disseminates insecticide from an impregnated net was evaluated in a randomized trial of 200 houses in Mexico. The devices were introduced at a rate of 1 per room and replaced at 3-week intervals. During each of 7 consecutive deployment cycles, indoor resting mosquitoes were sampled using aspirator collections. Assessments of mosquito landing behaviours were made in a subset of houses. Pre-treatment, there were no differences in Aedes aegypti indices between houses recruited to the control and treatment arms. Immediately after metofluthrin deployment, the entomological indices between the trial arms diverged. Averaged across the trial, there were significant reductions in Abundance Rate Ratios for total Ae. aegypti, female abundance and females that contained blood meals (2.5, 2.4 and 2.3-times fewer mosquitoes respectively; P<0.001). Average efficacy was 60.2% for total adults, 58.3% for females, and 57.2% for blood-fed females. The emanators also reduced mosquito landings by 90% from 12.5 to 1.2 per 10-minute sampling period (P<0.05). Homozygous forms of the pyrethroid resistant kdr alleles V410L, V1016L and F1534C were common in the target mosquito population; found in 39%, 24% and 95% of mosquitoes collected during the trial. This is the first randomized control trial to evaluate the entomological impact of any volatile pyrethroid on urban Ae. aegypti. It demonstrates that volatile pyrethroids can have a sustained impact on Ae. aegypti population densities and human-vector contact indoors. These effects occur despite the presence of pyrethroid-resistant alleles in the target population. Formulations like these may have considerable utility for public health vector control responses.

Background Spatial repellents can provide personal and household protection against biting vector mosquitoes by volatizing repellents into the air within a given area. Mosquito Shield™ is a transfluthrin passive emanator undergoing evaluation for malaria control. Studies evaluating its entomological impact against different local malaria vector populations would help guide its deployment in endemic countries. Methods A two-arm single-blinded small-scale household randomised entomological trial was conducted to assess the impact of Mosquito Shield™ on the human landing rate of wild pyrethroid-resistant Anopheles gambiae sensu lato ( s.l .) vector mosquitoes in houses in the Ganhoua village of the Zakpota District of central Benin. From a total of 30 houses, 15 were randomly allocated to receive Mosquito Shield™, while the remainder received a placebo product. The trial lasted through the life of the Mosquito Shield™ product (32 days). Mosquito sampling was performed by human landing catches at baseline and at 6 timepoints post-intervention (days 0–1, 7–8, 14–15, 21–22, 28–29 and 31–32). Collections were performed for 2 nights at each sampling time point. WHO cylinder bioassays were conducted during the trial with F1 An. gambiae s.l. mosquitoes that emerged from larvae from the study area to assess the intensity of resistance to pyrethroids in the wild vector population. Results The vector population in the study area showed a high intensity of resistance to pyrethroids. Baseline An. gambiae s.l. human landing rates were similar in houses in both study arms before product application (11.53/person/night vs 11.67/person/night, p > 0.05). A total of 5736 mosquitoes were collected in the placebo control arm and 3862 in the Mosquito Shield™ arm post-intervention. Overall An. gambiae s.l. post-intervention human landing rates were significantly lower in houses in the Mosquito Shield™ arm (18.13/person/night) compared to the houses in the placebo control arm (26.84/person/night, IRR = 0.658, p < 0.001). Over the lifespan of the product, Mosquito Shield™ provided a significant protective efficacy of 34.2% (22.1–44.4%, p < 0.001) against wild pyrethroid-resistant An. gambiae s.l. vectors compared to the placebo. Human landing rates of other nuisance vector mosquito species ( Culex and Mansonia ) were also reduced in houses treated with Mosquito Shield™ compared to the placebo. Conclusion Mosquito Shield™, a transfluthrin passive emanator, provided significant protection against pyrethroid-resistant malaria vectors to households in Benin. The spatial repellent shows potential to reduce malaria transmission by pyrethroid-resistant An. gambiae s.l. vector mosquitoes and cover gaps in malaria control when deployed to complement existing vector control interventions.

Spatial emanators (SE) are innovative tools for controlling indoor Aedes aegypti due to their relatively easy use and high efficacy. Large-scale implementation challenges include community adoption, particularly ensuring proper installation and timely replacement as SE efficacy wanes. We conducted a three-arm, open-label entomological cluster randomized controlled trial with a crossover design, involving 588 households, to assess the entomological effect of the community use of metofluthrin emanators. Arms were: \"no treatment\"; \"community-led deployment\" (CD), where the households were responsible for installing and replacing SE with minimal guidance; and \"managed deployment\" (MD), where the research team handled SE installation and replacement. Emanators were replaced every 3 weeks across four deployment cycles, followed by a crossover between the CD and MD arms. Indoor resting mosquitoes were collected using Prokopack aspirators, and human landing counts (HLCs) were conducted in a subset of 12 houses (4 by arm) at the first, fourth, fifth, and eighth SE replacement rounds. Values of each endpoint during all sampling periods were compared using generalized linear mixed effects models (GLMM), the coefficients of the best-fitting model estimated that SE intervention reduced the number of Ae. aegypti per house by 32.7% (95%CI = 16.2-46.0%) in the CD arm and 36.8% (21.1-49.3%) in the MD arm. HLCs accounted 74-94% efficacy (MD) and 35-79% (CD). The crossover analysis found no significant difference between periods and arms, demonstrating the community's ability to manage SE as effectively as research team, even without prior training. This trial suggests that safe, portable SE are suited to deployment by householders as a rapid response to local Aedes-borne disease outbreaks even in the presence of high pyrethroid resistance in the local Aedes population. In urban areas where effective coverage and resourcing is a challenge to control campaigns, community \"ownership\" of SE products may enhance the impact of insecticidal interventions.

Background: Statin therapy has been reported to be associated with new-onset diabetes. Angiotensin II-receptor blockers (ARBs) are effective antihypertensive drugs that have been reported to activate peroxisome proliferator-activated receptor γ (PPARγ) to differing extents, with favorable effects on glucose metabolism and the incidence of new-onset diabetes. Among the ARBs, telmisartan is a partial activator of PPARγ, irbesartan is a weak partial activator, and olmesartan has no effect on PPARγ activation. Objective: The goal of this study was to evaluate the effects on glucose homeostasis of combining rosuvastatin with ARBs of varying PPARγ-activating potency in Greek adults with impaired fasting glucose, mixed dyslipidemia, and stage 1 hypertension. Methods: This was a 24-week, randomized, open-label study. Inclusion criteria were impaired fasting plasma glucose (FPG) (100–125 mg/dL [5.6–6.9 mmol/L]), mixed dyslipidemia (LDL-C >160 mg/dL [4.14 mmol/L] and triglycerides >150 mg/dL [1.69 mmol/L]), and stage 1 hypertension (systolic blood pressure 140–159 mm Hg and/or diastolic blood pressure 90–99 mm Hg). After 12 weeks of dietary intervention, patients were randomly allocated to receive rosuvastatin 10 mg/d plus telmisartan 80 mg/d (RT group), irbesartan 300 mg/d (RI group), or olmesartan 20 mg/d (RO group) for 24 weeks. The primary end point was change in the following indices of glucose metabolism after 6 months of treatment: FPG, homeostasis model assessment of insulin resistance (HOMA-IR), HOMA of β-cell function (HOMA-B), and glycosylated hemoglobin (HbA 1c). Secondary end points included changes in anthropometric variables, blood pressure, serum lipids, and high-sensitivity C-reactive protein (hs-CRP). Tolerability was monitored throughout the study. Results: After the 12-week dietary intervention, 151 white patients (78 female, 73 male) met the inclusion criteria and were randomized to receive RT (n = 52), RI (n = 48), or RO (n = 51). The mean (SD) age of the 3 groups was 60 (10), 60 (10), and 58 (12) years, respectively; their mean weight was 79 (11), 81 (12), and 78 (11) kg. At 6 months, the RT group had a 29% decrease in HOMA-IR (from a median [range] of 2.6 [0.6–6.6] to 1.8 [0.5–5.1]), the RI group had a 16% increase (from 2.5 [0.5–6.2] to 2.9 [0.5–8.1]), and the RO group had a 14% increase (from 2.4 [0.5–7.9] to 2.7 [0.5–5.2]) (all, P < 0.05 vs baseline). The improvement in the RT group was statistically significant compared with the RI group ( P < 0.01) and the RO group ( P < 0.05). The changes from baseline in FPG and HbA 1c were not significant in any group. Fasting serum insulin decreased by 21% in the RT group (from 10.4 [2.4–28.1] to 8.2 [2.4–18.8] μU/mL), whereas it increased by 12% in the RI group (from 9.1 [2.0–26.5] to 10.2 [2.0–25.2] μU/mL) and by 8% in the RO group (from 10.1 [2.0–29.6] to 10.9 [2.0–19.1] μU/mL) (all, P < 0.05 vs baseline). Again, there was a significant difference between the RT group and the RI group ( P < 0.01) and RO group ( P < 0.05). Levels of hs-CRP decreased by 44% in the RT group (from 2.2 [0.3–7.9] to 1.2 [0.4–7.0] mg/L), by 12% in the RI group (from 2.2 [0.3–12.3] to 1.9 [0.2–11.4] mg/L), and by 22% in the RO group (from 2.1 [0.7-4.0] to 1.7 [0.7–6.2] mg/L). The difference was statistically significant for the RT group compared with baseline and with the RI and RO groups (all comparisons, P < 0.05). Blood pressure was significantly reduced from baseline in all 3 groups, with no significant differences between groups. No serious adverse events were reported during the study, nor were there any clinically significant elevations in aminotransferases or creatine kinase. Conclusion: In this small, randomized, open-label study, the RT combination had favorable effects on HOMA-IR, fasting serum insulin, and hs-CRP compared with the RI and RO combinations in Greek adults with impaired fasting glucose, mixed hyperlipidemia, and stage 1 hypertension.

Background and Objectives Administration of a loading dose of a statin (HMG-CoA reductase inhibitor) prior to percutaneous coronary intervention (PCI) contributes to protection from myocardial ischemic–reperfusion injury. This trial was designed to investigate the effect and mechanism of loading-dose rosuvastatin therapy before PCI in patients with acute coronary syndrome. Methods One hundred and forty-three patients with acute coronary syndrome were randomized to either the loading-dose (rosuvastatin 40 mg given 4 h before PCI) or conventional-dose (rosuvastatin 10 mg given 4 h before PCI) group. Blood samples were collected before and 0, 24, and 72 h post-PCI for measurement of serum cardiac troponin-I (cTn I), creatine kinase-MB (CK-MB), superoxide dismutase (SOD), reactive oxygen species (ROS), and malondialdehyde (MDA). Echocardiography and the major adverse cardiac/cerebrovascular events (MACCE) rate were followed up for 6 months post-PCI. Results Blood serum CK-MB and cTn I were significantly lower in the loading-dose group than in the conventional-dose group at 24 and 72 h post-PCI [CK-MB: 26.90 ± 3.22 vs. 32.96 ± 2.65 IU/L, P  = 0.024; 10.79 ± 4.65 vs. 15.18 ± 5.39 IU/L, P  = 0.021. cTn I: 0.046 ± 0.007 vs. 0.055 ± 0.002 ng/mL, P  = 0.015; 0.027 ± 0.006 vs. 0.041 ± 0.006 ng/mL, P  = 0.026]. Echocardiography at 6 months after PCI revealed significant improvement in cardiac function in the loading-dose group compared with the conventional-dose group ( P  < 0.05). The MACCE rate at 6 months after PCI in the loading-dose group was lower than in the conventional-dose group ( P  = 0.0428). The levels of MDA and ROS were decreased and the SOD level was significantly higher in the loading-dose group than in the conventional-dose group at 0, 24, and 72 h post-PCI ( P  < 0.05). Conclusion Administration of loading-dose rosuvastatin in patients with acute coronary syndrome prior to PCI exerts myocardial protection by inhibition of oxidative stress.

Serum creatinine–based estimates of glomerular filtration rate (eGFR) are frequently used to identify patients with chronic kidney disease and assess cardiovascular risk both in clinical trials and in clinical practice. Although change in eGFR may be useful to assess change in renal function in patients with chronic kidney disease, the utility of serum creatinine–based eGFR is uncertain, particularly among individuals with normal or only mildly impaired renal function. The goal of this study was to examine the relationship between baseline serum creatinine and eGFR, as well as changes in these parameters, in apparently healthy adults in a post hoc analysis of data obtained in participants in the JUPITER study (Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin). JUPITER was a randomized study of rosuvastatin 20 mg versus placebo in apparently healthy adults with high-sensitivity C-reactive protein levels ≥2.0 mg/L, LDL-C <130 mg/dL, and serum creatinine ≤2.0 mg/dL. Changes from baseline in serum creatinine and eGFR, based on the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations, were assessed in the entire population and in subsets classified according to baseline eGFR status. Baseline characteristics of the 16,279 JUPITER study participants (mean age, 66 years; 62% men; 72% white; and 58% with a history of hypertension) who had both a baseline and ≥1 postbaseline serum creatinine measurement were similar to the entire population of 17,802 patients who entered the trial. The mean age of the study population was 66 years, 62% were men, 72% were white, and 58% had a history of hypertension. Mean (SD) serum creatinine increased from baseline by 0.08 (0.16) mg/dL and 0.09 (0.14) mg/dL in the rosuvastatin and placebo groups, respectively ( P = 0.001) at year 1 and by 0.09 (0.18) and 0.10 (0.16) mg/dL ( P = 0.0045) at the final visit. Reductions in MDRD and CKD-EPI eGFR were ∼0.5 mL/min/1.73 m 2 greater with placebo than with rosuvastatin ( P < 0.004) at year 1 and the final visit. The magnitude of eGFR change was closely related to baseline eGFR, with greater reductions among subjects with eGFR ≥60 mL/min/1.73 m 2 in both the rosuvastatin and placebo groups. Among those with an eGFR ≥90 mL/min/1.73 m 2 , mean changes at year 1 and final visit ranged from –16 to –23 mL/min/1.73 m 2 with MDRD and CKD-EPI, respectively; in contrast, mean changes were <1 mL/min/1.73 m 2 in subjects with eGFR <60 mL/min/1.73 m 2 . In JUPITER, reductions in MDRD or CKD-EPI eGFR levels were greater in study participants with higher baseline eGFR levels but less in the rosuvastatin than in the placebo group. Future studies are required to assess the reliability of serum creatinine–based estimates of GFR to assess change in renal function, particularly among individuals with normal serum creatinine levels. ClinicalTrials.gov identifier: NCT00239681.

Preclinical and limited clinical data suggest that statins decrease the progressive decline in renal function that occurs in patients with renal disease. Pooled analysis of data obtained from a population of hyperlipidemic patients enrolled in the rosuvastatin (Crestor ® ) clinical development program permitted assessment of its effects on renal function both early and later in the course of treatment. Study participants were initially included in controlled clinical trials that evaluated the lipid-lowering efficacy and safety of rosuvastatin when compared with placebo or other lipid-lowering agents (i.e., atorvastatin, simvastatin, pravastatin, cholestyramine, fenofibrate or extended-release niacin). The median duration of treatment with the various doses of statins in these trials was approximately 8 weeks. Following completion of a controlled clinical trial, patients were permitted to enter an open-label extension trial and received rosuvastatin treatment. These data permitted assessment of renal function in a diverse group of over 10,000 patients who received rosuvastatin in its recommended dose range (5–40 mg) for up to 3.8 years. Mean serum creatinine concentrations were lower when compared with baseline both early and later in the course of rosuvastatin treatment. In contrast, no change in mean serum creatinine was observed with placebo. Mean glomerular filtration rates (GFR) predicted from the Modification of Diet in Renal Disease (MDRD) equation were higher when compared with baseline both early and later in the course of rosuvastatin treatment. No change in GFR was observed in the placebo group. Among patients who received long-term rosuvastatin treatment (≧96 weeks), GFR was unchanged or tended to increase, rather than decrease, when compared with baseline irrespective of age, gender, hypertensive or diabetic status, level of renal function (GFR ≧60 vs. <60 ml/min/1.73 m 2 ) at entry or urine dipstick protein status prior to or during the period of treatment. These findings suggest that rosuvastatin may arrest the progression of renal disease.

Background Statins are frequently administered to reduce low-density lipoprotein cholesterol (LDL-C) and vascular inflammation, because LDL-C and high sensitive C-reactive protein (hs-CRP) are associated with high risk for cardiovascular events. When statins do not reduce LDL-C to desired levels in high-risk patients with coronary artery disease (CAD), ezetimibe can be added or the statin dose can be increased. However, which strategy is more effective for treating patients with CAD has not been established. The present study compares anti-inflammatory effects and lipid profiles in patients with CAD and similar LDL-C levels who were treated by increasing the statin dose or by adding ezetimibe to the original rosuvastatin dose to determine the optimal treatment for such patients. Methods 46 patients with high-risk CAD and LDL-C and hs-CRP levels of >70 mg/dL and >1.0 mg/L, respectively, that were not improved by 4 weeks of rosuvastatin (2.5 mg/day) were randomly assigned to receive 10 mg (R10, n = 24) of rosuvastatin or 2.5 mg/day of rosuvastatin combined with 10 mg/day of ezetimibe (R2.5/E10, n = 22) for 12 weeks. The primary endpoint was a change in hs-CRP. Results Baseline characteristics did not significantly differ between the groups. At 12 weeks, LDL-C and inflammatory markers (hs-CRP, interleukin-6, tumour necrosis factor-alpha and pentraxin 3) also did not significantly differ between the two groups (LDL-C: R10 vs. R2.5/E10: -19.4 ± 14.2 vs. -22.4 ± 14.3 mg/dL). However, high-density lipoprotein cholesterol (HDL-C) was significantly improved in the R10, compared with R2.5/E10 group (4.6 ± 5.9 vs. 0.0 ± 6.7 mg/dL; p < 0.05). Conclusion Both enhanced therapies exerted similar anti-inflammatory effects under an equal LDL-C reduction in patients with high-risk CAD despite 2.5 mg/day of rosuvastatin. However, R10 elevated HDL-C more effectively than R2.5/E10. Trial registration UMIN000003746

Elevated C-reactive protein (CRP) is a common finding in patients with aortic stenosis (AS) and may be associated with rapid AS progression and worse outcome. The purpose of the study was to examine the role of high-sensitivity CRP and its interaction with rosuvastatin on the progression of AS. We measured CRP at baseline, 1 year, and end of follow-up in 260 patients with a median follow-up of 3.5 years. Analyses were performed based on baseline CRP tertiles and baseline CRP >3 and ≤3 mg/L. After adjustment for baseline characteristics, higher CRP levels were associated with age, female gender, body mass index, and lower high-density lipoprotein cholesterol levels but not with AS severity. Treatment with rosuvastatin led to a persistent decrease in CRP at 1 year and end of follow-up. Progression of AS was detected in patients in all 3 CRP tertiles, and rosuvastatin treatment had no impact on progression in all 3 tertiles. Similar findings were observed using CRP >3 mg/L as the cutpoint. Multiple linear regression showed that baseline AS velocity (P < .001), but not CRP, was the only predictor of progression of AS; age (P = .05) and baseline AS velocity (P < .001), but not CRP and rosuvastatin treatment, were predictors of outcome events. C-reactive protein does not predict severity, progression, and prognosis in patients with mild to moderate AS. Treatment with rosuvastatin reduces CRP levels but has no effect on the progression and clinical events of AS.