Bayesian network meta-regression hierarchical models using heavy-tailed multivariate random effects with covariate-dependent variances.

Network meta-analysis (NMA) is gaining popularity in evidence synthesis and network meta-regression allows us to incorporate potentially important covariates into network meta-analysis. In this article, we propose a Bayesian network meta-regression hierarchical model and assume a general multivariate t distribution for the random treatment effects. The multivariate t distribution is desired for heavy-tailed random effects and converges to the multivariate normal distribution when the degrees of freedom go to infinity. Moreover, in NMA, some treatments are compared only in a single study. To overcome such sparsity, we propose a log-linear regression model for the variances of the random effects and incorporate aggregate covariates into modeling the variance components. We develop a Markov chain Monte Carlo sampling algorithm to sample from the posterior distribution via the collapsed Gibbs technique. We further use the deviance information criterion and the logarithm of the pseudo-marginal likelihood for model comparison. A simulation study is conducted and a detailed analysis from our motivating case study is carried out to further demonstrate the proposed methodology.

Biphasic Postnatal Umbilical Cord Shortening.

INTRODUCTION: Variations in postnatal length of refrigerated, unfixed umbilical cords were studied over time to elucidate natural changes and times of stability. METHODS: Length was measured in 132 cords following severance, repeated at varying timed intervals and studied by analysis of variance and regression analysis. RESULTS: Data show immediate rapid initial phase shortening (mean 4.2+/-3.9 cm SD); an interval of lengthening; stable length at hours 3-4 following severance, a slower second phase shortening (mean 1.5+/-0.7 cm SD) beginning at 5 hours and peaking at 12 hours; and gradual lengthening to stable length after 23 hours. Overall, there was a significant net mean decrease of 3.49+/-2.29 cm SD. Shortening was greatest for intact long cord segments (p=0.0001), as much as 11 cm. Two highly significant models for predicting umbilical cord length at delivery (OL) were determined using the post-delivery lengths (Length) measured at different times following delivery (Hours), as follows:At ≤ 3 hours following delivery: OL=1.02xLength cm+1.11xHoursAt >3 hours following delivery: OL=1.07xLength+0.44xHours-0.01x(Hours)2. CONCLUSION: Cord lengths stabilized between hours 3-4 and after 23 hours following severance. Phase one shortening resembles vasoconstriction; phase two resembles rigor mortis. The models allow prediction of the original umbilical cord length at delivery, regardless of the time of measurement.

Bayesian inference for network meta-regression using multivariate random effects with applications to cholesterol lowering drugs.

Low-density lipoprotein cholesterol (LDL-C) has been identified as a causative factor for atherosclerosis and related coronary heart disease, and as the main target for cholesterol- and lipid-lowering therapy. Statin drugs inhibit cholesterol synthesis in the liver and are typically the first line of therapy to lower elevated levels of LDL-C. On the other hand, a different drug, Ezetimibe, inhibits the absorption of cholesterol by the small intestine and provides a different mechanism of action. Many clinical trials have been carried out on safety and efficacy evaluation of cholesterol lowering drugs. To synthesize the results from different clinical trials, we examine treatment level (aggregate) network meta-data from 29 double-blind, randomized, active, or placebo-controlled statins +/$-$ Ezetimibe clinical trials on adult treatment-naïve patients with primary hypercholesterolemia. In this article, we propose a new approach to carry out Bayesian inference for arm-based network meta-regression. Specifically, we develop a new strategy of grouping the variances of random effects, in which we first formulate possible sets of the groups of the treatments based on their clinical mechanisms of action and then use Bayesian model comparison criteria to select the best set of groups. The proposed approach is especially useful when some treatment arms are involved in only a single trial. In addition, a Markov chain Monte Carlo sampling algorithm is developed to carry out the posterior computations. In particular, the correlation matrix is generated from its full conditional distribution via partial correlations. The proposed methodology is further applied to analyze the network meta-data from 29 trials with 11 treatment arms.

Comparative analysis of retrograde intrarenal surgery and modified ultra-mini percutaneous nephrolithotomy in management of lower pole renal stones (1.5-3.5 cm).

BACKGROUND: To compare the safety and efficacy of retrograde intrarenal surgery (RIRS) and modified Ultra-mini percutaneous nephrolithotomy (UMP) in semi-supine combined lithotomy position for the management of 1.5-3.5 cm lower pole renal stones (LPSs). METHODS: A total of 63 patients with 1.5-3.5 cm LPSs who underwent RIRS (n = 33) or modified UMP (n = 30) in diameter between January 2017 and January 2019 were analyzed retrospectively. Modified UMP was performed in semi-supine combined lithotomy position and a 9.5/11.5 F ureteral access sheath (UAS) was inserted during the procedure in order to maintain low pelvic pressure and to facilitate the removal of stone fragments. Base-line parameters, stone characteristics, illness condition, operation time, postoperative hemoglobin (Hb) drop, postoperative creatinine (Cr) elevation, length of hospital stay, length of postoperative hospital stay, stone-free rate (SFR) and complications were compared between the two groups. RESULTS: There were no significant differences between the two groups in base-line parameters, stone characteristics and illness condition. The mean operating time of RIRS group was longer than UMP group (95.61 ± 21.9 vs. 55.0 ± 16.1 min, p < 0.001). The mean postoperative Hb drop was less in RIRS group (7.42 ± 4.7 vs. 15.70 ± 9.8 g/L, p < 0.001). The length of hospital stay and postoperative hospital stay for RIRS were shorter than UMP (4.76 ± 1.1 vs. 5.83 ± 0.8 d, p < 0.001, 2.97 ± 0.9 vs. 4.07 ± 0.9 d, p < 0.001). The Early SFR was higher in UMP group (54.5 vs. 80.0%, p < 0.050) while SFR at 1-month and 3-months postoperatively was similar in both groups (p = 0.504, p = 0.675). There were no significant differences between the two groups in complications (p = 0.228). CONCLUSION: For patients with 1.5-3.5 cm LPSs, both modified UMP and RIRS are safe and viable. The modified UMP technique was used in this study, application semi-supine combined lithotomy position and the retention of UAS can improve the surgical efficiency and maintain low pressure perfusion in the kidney, which resulted in superior treatment efficacy. Therefore, we highly recommend this technique for LPSs with heavy stone burdens.

Influence of metabolic syndrome factors and insulin resistance on the efficacy of ezetimibe/simvastatin and atorvastatin in patients with metabolic syndrome and atherosclerotic coronary heart disease risk.

BACKGROUND: Metabolic syndrome (MetS) and insulin resistance (IR) are increasing in prevalence, are associated with higher risk for coronary heart disease (CHD), and may potentially influence the responses to lipid-altering drug therapy. This study evaluated the effects of MetS factors (abdominal obesity, depleted high-density lipoprotein cholesterol [HDL-C], and elevated triglycerides, blood pressure, and fasting glucose) and IR on ezetimibe/simvastatin and atorvastatin treatment efficacy in patients with MetS. METHODS: This post-hoc analysis of a multicenter, 6-week, double-blind, randomized, parallel group study of 1128 subjects with hypercholesterolemia, MetS, and moderately high/high CHD risk evaluated the effects of baseline MetS factors/IR on percent change from baseline in lipids, apolipoproteins, and high-sensitivity C-reactive protein (hs-CRP), after treatment with the usual starting doses of ezetimibe/simvastatin (10/20 mg) versus atorvastatin (10 mg, 20 mg) and next higher doses (10/40 mg versus 40 mg). RESULTS: Ezetimibe/simvastatin and atorvastatin efficacy was generally consistent across MetS factor/IR subgroups. Ezetimibe/simvastatin produced greater incremental percent reductions in LDL-C, non-HDL-C, apolipoprotein B, total cholesterol, and lipoprotein ratios for all subgroups, and larger percent increases in HDL-C and apolipoprotein AI for all but non-obese and HDL-C ≥ 40 mg/dL subgroups than atorvastatin at the doses compared. Triglycerides, very-LDL-C, and hs-CRP results were more variable but similar between treatment groups. CONCLUSION: The magnitude of lipid-altering effects produced by each treatment regimen was generally similar across all MetS and IR subgroups. Ezetimibe/simvastatin produced greater percent reductions in most lipid fractions than atorvastatin at the dose comparisons studied, and all treatments were generally well tolerated. (Registered at clinicaltrials.gov: NCT00409773).

Bayesian inference for multivariate meta-analysis Box-Cox transformation models for individual patient data with applications to evaluation of cholesterol-lowering drugs.

In this paper, we propose a class of Box-Cox transformation regression models with multidimensional random effects for analyzing multivariate responses for individual patient data in meta-analysis. Our modeling formulation uses a multivariate normal response meta-analysis model with multivariate random effects, in which each response is allowed to have its own Box-Cox transformation. Prior distributions are specified for the Box-Cox transformation parameters as well as the regression coefficients in this complex model, and the deviance information criterion is used to select the best transformation model. Because the model is quite complex, we develop a novel Monte Carlo Markov chain sampling scheme to sample from the joint posterior of the parameters. This model is motivated by a very rich dataset comprising 26 clinical trials involving cholesterol-lowering drugs where the goal is to jointly model the three-dimensional response consisting of low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and triglycerides (TG) (LDL-C, HDL-C, TG). Because the joint distribution of (LDL-C, HDL-C, TG) is not multivariate normal and in fact quite skewed, a Box-Cox transformation is needed to achieve normality. In the clinical literature, these three variables are usually analyzed univariately; however, a multivariate approach would be more appropriate because these variables are correlated with each other. We carry out a detailed analysis of these data by using the proposed methodology.

Meta-analysis methods and models with applications in evaluation of cholesterol-lowering drugs.

In this paper, we propose a class of multivariate random effects models allowing for the inclusion of study-level covariates to carry out meta-analyses. As existing algorithms for computing maximum likelihood estimates often converge poorly or may not converge at all when the random effects are multi-dimensional, we develop an efficient expectation-maximization algorithm for fitting multi-dimensional random effects regression models. In addition, we also develop a new methodology for carrying out variable selection with study-level covariates. We examine the performance of the proposed methodology via a simulation study. We apply the proposed methodology to analyze metadata from 26 studies involving statins as a monotherapy and in combination with ezetimibe. In particular, we compare the low-density lipoprotein cholesterol-lowering efficacy of monotherapy and combination therapy on two patient populations (naïve and non-naïve patients to statin monotherapy at baseline), controlling for aggregate covariates. The proposed methodology is quite general and can be applied in any meta-analysis setting for a wide range of scientific applications and therefore offers new analytic methods of clinical importance.

metapack: An R Package for Bayesian Meta-Analysis and Network Meta-Analysis with a Unified Formula Interface.

Meta-analysis, a statistical procedure that compares, combines, and synthesizes research findings from multiple studies in a principled manner, has become popular in a variety of fields. Meta-analyses using study-level (or equivalently aggregate) data are of particular interest due to data availability and modeling flexibility. In this paper, we describe an R package metapack that introduces a unified formula interface for both meta-analysis and network meta-analysis. The user interface-and therefore the package-allows flexible variance-covariance modeling for multivariate meta-analysis models and univariate network meta-analysis models. Complicated computing for these models has prevented their widespread adoption. The package also provides functions to generate relevant plots and perform statistical inferences like model assessments. Use cases are demonstrated using two real data sets contained in metapack.

Monopolar Transurethral Resection of Prostate for Benign Prostatic Hyperplasia in Patients With and Without Preoperative Urinary Catheterization: A Prospective Comparative Study.

Background A significant proportion of patients undergo surgery for benign prostatic hyperplasia following acute urinary retention. Studies have reported conflicting results of improvement following transurethral surgery in these patients. Objective To compare perioperative complications and postoperative voiding parameters in patients undergoing monopolar transurethral resection of prostate with and without preoperative Foley catheterization. Methods A prospective non-randomized study was conducted in patients undergoing monopolar transurethral resection of prostate for symptomatic benign prostatic hyperplasia. Patients were divided into those with Foley catheterization preoperatively (n=52), and those without catheters (n=90). Change in hemoglobin level, the resected volume of prostate, complications and the need for postoperative catheterization were compared. Postoperative symptoms score using International Prostate Symptom Score, maximum flow rate and post-void residual volume were assessed at three months follow up. Results The mean operative duration, length of stay and resected volume were higher in those patients with catheters; however, no significant differences were noted for mean hemoglobin level change and need for postoperative recatheterization. Three patients in each group required recatheterization and, all were catheter-free at one week postoperatively. Complications developed in 16.1% (n=23) with most of them being Clavien I. Patients with catheters had a lower postoperative maximum flow rate than those without it (16.90 vs 19.75 mL/sec). Patients with catheters had a significantly better postoperative quality of life and symptom score. Conclusion Monopolar transurethral resection of prostate in patients with preoperative per-urethral Foley catheter for acute urinary retention had similar postoperative voiding parameters with comparable complication rates to those without a catheter.

Elevated high sensitivity C-reactive protein levels in aging men with low testosterone.

OBJECTIVE: We examined baseline data from a lipid treatment study to assess the relationship between testosterone (T) and the cardiovascular inflammatory marker, high sensitivity C-reactive protein (hsCRP). METHODS: The baseline T, hsCRP, lipid, glycemic, and anthropometric data were obtained from 467 men (mean age: 52 years). Inclusion criteria included low-density lipoprotein cholesterol > or = 3.4 to 4.9 mmol/l and triglycerides < or = 4.0 mmol/l. The baseline hsCRP levels were examined across the following T subgroups: <6.9 nmol/l (moderate to severe hypogonadism), 6.9 to <10.4 nmol/l (mild to moderate hypogonadism), 10.4 to <15 nmol/l (low-normal T), and > or = 15 nmol/l (normal T). RESULTS: The median hsCRP levels were significantly (p = 0.041) different across the four T subgroups; patients in the lower T subgroups had higher median hsCRP levels than patients in the higher T subgroups. The percentage of men with elevated hsCRP (>2 mg/l) was also significantly (p = 0.038) different across the four T subgroups; 83% of men with T < 6.9 nmol/l had elevated hsCRP compared with 40% with T > or = 15 nmol/l. CONCLUSIONS: This analysis demonstrated an inverse relationship between serum T and hsCRP in aging men. Urologists need to be aware that low T levels may not only adversely affect sexual function but also may worsen cardiovascular risk in aging, hypogonadal men.

Increased occurrence of marked elevations of lipoprotein(a) in ageing, hypercholesterolaemic men with low testosterone.

OBJECTIVE: We previously examined the inverse relationship between total serum testosterone (T) and the occurrence of the metabolic syndrome in ageing men using baseline data from two lipid treatment studies. We further examined baseline data from a subset of US men participating in one of these two studies to assess the relationship between T and the cardiovascular risk factor lipid, lipoprotein(a) [Lp(a)]. METHODS: Baseline T, lipid, glycaemic and anthropometric data were obtained from 107 men (mean age: 55 years). Inclusion criteria included low-density lipoprotein cholesterol > or = 3.4-4.9 mmol/l and triglycerides < or = 4.0 mmol/l. Baseline Lp(a) levels were examined across the following baseline T subgroups: <15 nmol/l (low/low-normal T) and > or = 15 nmol/l (normal T). RESULTS: There was an overall trend for a higher incidence of clinically significant Lp(a) elevations in men with low T; 17.1% of men in the low/low-normal T subgroup had an Lp(a) level > or = 3 times the upper limit of normal compared to 8.1% in the normal T subgroup. CONCLUSIONS: The data from this descriptive analysis suggest that ageing men with low serum T levels may have an increase in marked elevations in Lp(a), which would be expected to be associated with a significant increase in their cardiovascular event risk.

Effect of Dipeptidyl Peptidase 4 Inhibitors Used in Combination with Insulin Treatment in Patients with Type 2 Diabetes: A Systematic Review and Meta-analysis.

INTRODUCTION: To evaluate the efficacy and safety of dipeptidyl peptidase 4 inhibitors (DPP4i) used in combination with insulin in patients with type 2 diabetes mellitus (T2DM). METHODS: We searched the MEDLINE, Embase, and Cochrane library databases for randomized controlled trials (RCTs) published through June 2018. Studies with at least a 12-week treatment period were included to compare the addition of DPP4i to insulin with insulin control therapy. Meanwhile, groups on a stable insulin dosage (insulin-stable subgroup) or titrating insulin dosage (insulin-flexible subgroup) were analyzed separately. RESULTS: Twenty-one RCTs with 3697 patients randomized to a DPP4i/insulin treatment arm and 3538 to an insulin control arm were included. DPP4i, when added to insulin therapy, led to a significantly greater reduction in HbA1c (- 0.57%, 95% CI - 0.66, - 0.48) and provided significantly greater odds of achieving the HbA1c target < 7% (OR 3.45; 95% CI 2.58, 4.63). These effects were achieved in the context of a decrease in the daily insulin requirement, without increases in hypoglycemia risk and body weight, compared with the control treatment. Subgroup analysis showed control-adjusted reductions in HbA1c from baseline in the insulin-stable subgroup (-  0.64%; 95% CI - 0.74, - 0.53) and the insulin-flexible subgroup (- 0.43%; 95% CI - 0.56, - 0.30). Other results occurred similarly in both subgroups. CONCLUSIONS: The addition of DPP4i to insulin is associated with a statistically significant reduction in glycemic control as measured by HbA1c, fasting plasma glucose, and 2-h postprandial glucose, without increasing the risk of hypoglycemia and weight gain. These conclusions were also observed in both stable-dose and flexible-dose insulin subgroups.

Bayesian multivariate skew meta-regression models for individual patient data.

We examine a class of multivariate meta-regression models in the presence of individual patient data. The methodology is well motivated from several studies of cholesterol-lowering drugs where the goal is to jointly analyze the multivariate outcomes, low density lipoprotein cholesterol, high density lipoprotein cholesterol, and triglycerides. These three continuous outcome measures are correlated and shed much light on a subject's lipid status. One of the main goals in lipid research is the joint analysis of these three outcome measures in a meta-regression setting. Since these outcome measures are not typically multivariate normal, one must consider classes of distributions that allow for skewness in one or more of the outcomes. In this paper, we consider a new general class of multivariate skew distributions for multivariate meta-regression and examine their theoretical properties. Using these distributions, we construct a Bayesian model for the meta-data and develop an efficient Markov chain Monte Carlo computational scheme for carrying out the computations. In addition, we develop a multivariate L measure for model comparison, Bayesian residuals for model assessment, and a Bayesian procedure for detecting outlying trials. The proposed multivariate L measure, Bayesian residuals, and Bayesian outlying trial detection procedure are particularly suitable and computationally attractive in the multivariate meta-regression setting. A detailed case study demonstrating the usefulness of the proposed methodology is carried out in an individual patient data multivariate meta-regression setting using 26 pivotal Merck clinical trials that compare statins (cholesterol-lowering drugs) in combination with ezetimibe and statins alone on treatment-naïve patients and those continuing on statins at baseline.

Can initial vaginal bleeding patterns in etonogestrel implant users predict subsequent bleeding in the first 2 years of use?

OBJECTIVES: To evaluate if a simple method for characterizing vaginal bleeding patterns in etonogestrel contraceptive implant users can predict subsequent patterns and bleeding-related discontinuation over the first 2 years of use. STUDY DESIGN: We reanalyzed phase 3 study bleeding data for non-breastfeeding participants from the United States, Europe, Russia and Chile during the first 2 years of implant use to characterize and correlate bleeding patterns. We used 90-day reference periods with period 1.1 starting at Day 29 and ending at Day 118. We dichotomized bleeding patterns as "favorable" (amenorrhea, infrequent bleeding and normal frequency bleeding without prolonged bleeding) or "unfavorable' (prolonged and/or frequent bleeding) and tracked user groups based on these bleeding patterns in reference period 1.1 through Year 1 and from Year 1 through Year 2, respectively. RESULTS: We evaluated data from 537 and 428 women with up to 1 and 2 years use, respectively. Of the 325 (60.5%) women with favorable bleeding in reference period 1.1, 275 (84.6%) reported favorable bleeding also in reference period 2, 197 (60.6%) reported favorable bleeding throughout Year 1, and favorable bleeding in 75-85% of reference periods in Year 2. Among 212 (39.5%) women with unfavorable bleeding in reference period 1.1, 118 (55.7%) continued with unfavorable bleeding in reference period 2, while about 40%-50% reported favorable patterns in RP 2, 3 and/or 4. Initial favorable bleeding resulted in lower discontinuation rates than initial unfavorable bleeding in years 1 (3.7% vs 12.7%, p≪.0001) and 2 (2.5% vs 16.5%, p≪.0001). CONCLUSION: Implant users with favorable bleeding in the first reference period are likely to continue with favorable bleeding over the next 2 years. Initial bleeding patterns predict overall continuation rates in years 1 and 2. Implications Statement When evaluating vaginal bleeding in any 90-day reference period over 2 years of etonogestrel implant use, approximately 80% of women with favorable and 40% with unfavorable bleeding patterns will have favorable bleeding in the next reference periods. These findings can facilitate counseling regarding bleeding for women using the etonogestrel implant.

Long-term treatment with finasteride 1 mg decreases the likelihood of developing further visible hair loss in men with androgenetic alopecia (male pattern hair loss).

There are no reports on the effects of pharmacologic treatment on the likelihood of developing further visible hair loss in men with androgenetic alopecia (AGA). Our objectives were to examine whether finasteride 1 mg treatment decreases the likelihood of developing further visible hair loss in men with AGA. We conducted an analysis of global photographic assessment data from two Phase III trials in which 1553 men with AGA received finasteride 1 mg/day or placebo for up to 5 years. Finasteride 1 mg treatment led to a 93% decrease relative to placebo in the 5-year likelihood of developing further visible hair loss (95% CI: 89-97%; p < 0.001). We conclude that, in men with AGA, treatment with finasteride 1 mg/day over 5 years led to a marked and sustained decrease in the likelihood of developing further visible hair loss.

Progression of hair loss in men with androgenetic alopecia (male pattern hair loss): long-term (5-year) controlled observational data in placebo-treated patients.

Relatively little is known about the progression of androgenetic alopecia (AGA; male pattern hair loss) in untreated men. We evaluated the long-term (5-year) progression of AGA in men treated with placebo in a controlled clinical trial setting. We analyzed pooled data over 5 years from two replicate studies with finasteride 1 mg/day in men with predominantly vertex-pattern AGA. Each study consisted of an initial 1-year, randomized, double-blind, placebo-controlled base study and four consecutive, 1-year, double-blind, placebo-controlled extension studies. Change over time in scalp hair growth was evaluated by four predefined endpoints: scalp hair counts; assessment of standardized clinical photographs by an expert panel; investigator clinical assessment; and patient self-assessment. All four predefined endpoints demonstrated progressive scalp hair loss in men receiving placebo over the 5-year study period, with a loss of 239 hairs from baseline (26.3% decline in hair density) measured in the target area at 5 years (p < 0.001 vs. baseline). Similarly, visible progression of scalp hair loss was demonstrated by global photographic assessment, with 75% of placebo patients rated as worsened from baseline at 5 years. We found that scalp hair loss continued in a progressive manner over a 5-year period in placebo-treated men with AGA.

Bayesian Inference for Multivariate Meta-regression with a Partially Observed Within-Study Sample Covariance Matrix.

Multivariate meta-regression models are commonly used in settings where the response variable is naturally multi-dimensional. Such settings are common in cardiovascular and diabetes studies where the goal is to study cholesterol levels once a certain medication is given. In this setting, the natural multivariate endpoint is Low Density Lipoprotein Cholesterol (LDL-C), High Density Lipoprotein Cholesterol (HDL-C), and Triglycerides (TG) (LDL-C, HDL-C, TG). In this paper, we examine study level (aggregate) multivariate meta-data from 26 Merck sponsored double-blind, randomized, active or placebo-controlled clinical trials on adult patients with primary hypercholesterolemia. Our goal is to develop a methodology for carrying out Bayesian inference for multivariate meta-regression models with study level data when the within-study sample covariance matrix S for the multivariate response data is partially observed. Specifically, the proposed methodology is based on postulating a multivariate random effects regression model with an unknown within-study covariance matrix Σ in which we treat the within-study sample correlations as missing data, the standard deviations of the within-study sample covariance matrix S are assumed observed, and given Σ, S follows a Wishart distribution. Thus, we treat the off-diagonal elements of S as missing data, and these missing elements are sampled from the appropriate full conditional distribution in a Markov chain Monte Carlo (MCMC) sampling scheme via a novel transformation based on partial correlations. We further propose several structures (models) for Σ, which allow for borrowing strength across different treatment arms and trials. The proposed methodology is assessed using simulated as well as real data, and the results are shown to be quite promising.

Implementation of Ultramini Percutaneous Nephrolithotomy for Treatment of 2-3 cm Kidney Stones: A Preliminary Report.

BACKGROUND AND PURPOSE: Miniatured percutaneous nephrolithotomy (PCNL) techniques such as micro-PCNL (microperc) and ultramini-PCNL (UMP) are usually indicated for renal stones <2 cm. We present our preliminary report of treating patients with 2 to 3 cm renal stones using UMP in a semisupine combined lithotomy position associated with a retrograde ureteral access sheath (UAS). METHODS: From April 2013 to January 2014, we implemented 13F UMP for 22 patients with renal stones that were 2 to 3 cm with the patient positioned in a 45-degree semisupine combined lithotomy position. A retrograde 9.5/11.5F UAS was placed for maintaining low intrarenal pressure and debris drainage. Flexible ureteroscopy was used for stones inaccessible through the primary percutaneous tract in two patients. A 200-µ holmium laser was used for stone disintegration. Intrapelvic pressure was measured using an open end 5F ureteral catheter inserted through the UAS. RESULTS: All 22 cases were completed successfully. The mean preoperative stone size was 26.6 ± 4.7 mm (range 21-32 mm), mean operative time was 85.7 ± 18.0 minutes (range 47-112 min), and mean hemoglobin drop was 1.2 ± 0.3 g/dL (range 0.5-2.2 g/dL). Intrapelvic pressure during the surgical procedure ranged 5 to 10 cm H2O. The mean hospital stay was 3.1 ± 1.8 days (range 2-5 d). Complete stone clearance was 18/22 (81.8%) with solo UMP and 20/22 (90.9%) when associated with retrograde intrarenal surgery (RIRS). No major intra- or postoperative complications occurred. CONCLUSION: Implementation of UMP for the treatment of patients with renal stones 2-3 cm is feasible and safe. The procedure is less invasive and has a faster recovery period. Intraoperative retrograde UAS decreases intrarenal pressure, facilitates removal of stone fragments, and also allows simultaneous RIRS for stones in an inaccessible calix.

Effects of simvastatin on C-reactive protein in mixed hyperlipidemic and hypertriglyceridemic patients.

This study examined the effects of simvastatin on C-reactive protein (CRP) and other inflammatory markers in study subjects with significant elevations in triglyceride (TG) blood levels. CRP, vascular cellular adhesion molecule (VCAM), serum amyloid A (SAA), and interleukin 6 (IL-6) were measured in archived plasma samples from 2 multicenter, randomized, double-blind, placebo-controlled studies designed to examine the lipid-altering efficacy of simvastatin in study subjects with elevated TGs. In the first study, 130 study subjects with mixed hyperlipidemia (low-density lipoprotein [LDL] cholesterol > or =130 mg/dl; TGs 300 to 700 mg/dl) received placebo or simvastatin 40 or 80 mg once daily for three 6-week periods in a complete-block crossover design. In the second study, 195 study subjects with hypertriglyceridemia (TGs 300 to 900 mg/dl) received daily doses of placebo or simvastatin 20, 40, or 80 mg for 6 weeks. Significant but weak correlations were observed between baseline CRP values and baseline levels of LDL cholesterol and high-density lipoprotein (HDL) cholesterol, but not with TGs. CRP was also correlated with body mass index and fasting levels of glucose and insulin. Treatment with simvastatin 20, 40, and 80 mg led to significant reductions in CRP plasma levels versus placebo (p <0.05). Although CRP change was weakly correlated with changes in LDL cholesterol, TGs, and HDL cholesterol, results of regression analyses showed that only baseline CRP and treatment allocation were significant predictors of CRP response after 6 weeks of study drug administration. Simvastatin had no effect on VCAM, SAA, or IL-6. In summary, simvastatin significantly reduced CRP in patients with mixed hyperlipidemia and hypertriglyceridemia.

Comparative effects of simvastatin and atorvastatin in hypercholesterolemic patients with characteristics of metabolic syndrome.

BACKGROUND: Hypercholesterolemic patients with metabolic syndrome (MS) are at high risk for coronary heart disease. The National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) guidelines provide the option of aggressively lowering low-density lipoprotein cholesterol (LDL-C) in hypercholesterolemic patients with MS. OBJECTIVE: The lipid-modifying efficacy of simvastatin and atorvastatin in hypercholesterolemic patients with MS as defined by NCEP ATP III was assessed. METHODS: A post hoc subgroup analysis was performed on data from a 36-week, multicenter (54 sites worldwide), randomized, double-blind, parallel-group, dose-escalation (forced-titration) study designed to assess the effects of simvastatin (40-80 mg) and atorvastatin (20-80 mg) on high-density lipoprotein cholesterol (HDL-C) and apolipoprotein (apo) A-I levels in patients with LDL-C > or = 160 mg/dL. Patients were classified as having MS if they met >/=3 of the following criteria: (1) triglyceride (TG) level > or =150 mg/dL; (2) HDL-C <40 mg/dL (men) or <50 mg/dL (women); (3) secondary diagnosis of type 2 diabetes mellitus and/or taking antidiabetic medication and/or fasting serum glucose (FSG) level > or =110 mg/dL; (4) secondary diagnosis of hypertension and/or taking antihypertensive medication and/or systolic blood pressure (SBP)/diastolic blood pressure (DBP) > or =130/ > or =85 mm Hg; and (5) body mass index (BMI) > or =30 kg/m(2) (surrogate for waist circumference). RESULTS: Of 808 evaluable patients, 212 (26.2%) were classified as having MS at baseline. Compared with the non-MS subgroup, MS patients were slightly older and more likely to be female. They also had higher BMI, SBP/DBP, FSG, and TG levels, and lower HDL-C and apo A-I levels than non-MS patients. The simvastatin group contained 99 patients; the atorvastatin group, 113 patients. Both drugs produced large reductions in total cholesterol, LDL-C, non-HDL-C, TG, and apo B, with atorvastatin producing slightly greater reductions in TG. However, simvastatin consistently produced larger increases in HDL-C and apo A-I than atorvastatin, especially at higher doses. After 36 weeks of treatment, 47.7% and 48.5% in the simvastatin and atorvastatin groups, respectively, no longer met > or =3 of the MS criteria. CONCLUSIONS: In hypercholesterolemic patients with characteristics of MS, simvastatin and atorvastatin had comparable beneficial effects on apo B-containing atherogenic lipids and lipoproteins, and MS status was effectively modified by both drugs. However, although atorvastatin produced slightly larger decreases in TG, simvastatin produced larger increases in HDL-C.