Predictive Factors for the Peri-operative Outcome of Ureteroscopic Lithotripsy for Proximal Ureteric Stones.

BACKGROUND: Proximal ureteric stones are considered one of challenging location for lithotripsy using semirigid ureteroscopes. Aim of the study was to assess clinical and radiological characteristics associated with outcome of lithotripsy using semirigid ureteroscope for proximal ureteric stones. METHODS: Prospective observational study was done on patients who underwent semirigid ureteroscopic lithotripsy for proximal ureteric stone. Stone and ureteral mormphomeric parameters were documented from computed tomography urogram. Stone free status and complication rates were studied. To determine predictive factors for outcomes, multivariate regression analysis and receiver operative curve were used. RESULTS: One hundred patients were included in study. Demographic characteristics, stone size, density and mode of lithotripsy had no impact on stone free rate or complications. The mean ureteral wall thickness(p = 0.002), distance of stone from pelvi-ureteric junction(p = 0.005), degree of hydronephrosis(p = 0.0001) and peri-ureteric fat stranding (p = 0.038) were found to have significant association with stone free rate on univariate analysis. On multivariate analysis, mild hydronephrosis(p = 0.003) and distance of stone from pelvi-ureteric junction(p = 0.022) were significant for stone free rate. CONCLUSIONS: Mean ureteral wall thickness, stone distance from pelvi-ureteric junction, presence of peri-ureteric fat stranding and hydronephrosis affect stone free rate on univariate analysis. On multivariate analysis for stone free rate, stone distance from pelvi-ureteric junction and mild hydronephrosis were significant. There was no significant impact of any stone or ureteral morphometry on complication rate.

Prostatic Urethral Length as a Predictor for Surgery in Benign Prostatic Hyperplasia.

BACKGROUND: Benign prostatic hyperplasia is associated with structural and morphological changes including elongation of prostatic urethral length. The aim of our study was to assess whether prostatic urethral length could predict need of surgery in patients with benign prostatic hyperplasia. METHODS: This prospective observational study was conducted over a 12-months duration. All the patients who presented with lower urinary tract symptoms secondary to benign prostatic hyperplasia were evaluated with International Prostate Severity Score, serum Prostate Specific Antigen, Transrectal Ultrasound was done to measure prostatic urethral length, prostate volume, Intravesical prostatic protusion and Post-void Residual Urine. Patients not responding to medical treatment and complications secondary to benign prostatic hyperplasia underwent surgery. Logistic regression analysis was performed to identify risk factors associated with surgery. RESULTS: A total of 153 patients were included in the study. Eighty-three (54.2%) patients underwent surgery during the study period. Prostate volume, intravesical prostatic protrusion, post-void residual volume, serum prostate specific antigen, and prostatic urethral length were significantly higher in the surgical group. The mean prostatic urethral length in the surgical group was 39.47 + 10.2 mm and in the nonsurgical group was 26.20 + 6.72 mm (p <0.0001). According to the ROC curve-based prediction of surgery, the area under the curve for PUL was 0.866 and the best cutoff value was 31.5mm (81% sensitivity and 84.3% specificity). CONCLUSIONS: BPH patients with longer PUL may require surgical management. PUL measured by TRUS may be a predicting factor for the need of surgery in BPH Keywords: Benign prostatic hyperplasia; lower urinary tract symptoms; prostatic urethral length.

Does Relocation of Lower Pole Stone During Retrograde Intrarenal Surgery Improve Stone-Free Rate? A Prospective Randomized Study.

Purpose: The aim of this study was to compare the stone-free rate (SFR) of in situ treatment vs relocation and lithotripsy for lower pole stones of less than 2 cm following retrograde intrarenal surgery (RIRS). Methods: This prospective randomized study was undertaken from June 2019 to May 2020 in patients undergoing RIRS for lower pole renal stones less than 2 cm in diameter. Patients were randomized into two groups: in situ lithotripsy group and relocation lithotripsy group. The in situ lithotripsy group underwent laser lithotripsy for lower pole stones without relocation of the calculus, and the relocation lithotripsy group had their stones relocated to a favorable location using a tipless Nitinol basket, followed by laser lithotripsy. Laser lithotripsy was achieved using the holmium:YAG (Ho:YAG) laser (120 W) with a 200-µm laser fiber. A Double-J stent was placed in all patients at the end of the procedure. Patient demographics, stone characteristics, operative outcomes, and complications were evaluated. The SFR was determined at 1 month postoperatively with a kidney, ureter, and bladder radiograph (KUB) and ultrasound KUB. Results: Sixty-eight patients were included in the study: in situ group (n = 35) and relocation group (n = 33). The mean stone size and stone density were similar between the groups. The total operative duration, lasing duration, and total energy used were similar between the groups. At the 1-month follow-up, the complete SFR was 85.7% and 91% in the in situ lithotripsy and relocation lithotripsy groups, respectively (p = 0.506). Conclusions: Relocation followed by subsequent laser lithotripsy was associated with similar SFRs as with in situ laser lithotripsy for lower pole renal calculi less than 2 cm in diameter following RIRS using the Ho:YAG laser.

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.

Comparative Study of Percutaneous Nephrolithotomy in Supine and Prone Positions.

BACKGROUND: The aim of the study is the compare efficacy and safety of percutaneous nephrolithotomy in supine and prone positions. Percutaneous nephrolithotomy is conventionally performed in prone position but in recent years numbers of supine percutaneous nephrolithotomies is increasing globally. METHODS: The hospital based cross-sectional observational study was conducted in the Department of Urology, Bir Hospital from July 2018 to January 2020. A total of 81 consecutive patients undergoing percutaneous nephrolithotomy were divided into two groups, with 38 patients in Supine (Group 1) and 43 patients in Prone (Group 2) positions, respectively. Patient's demographics, access time, operative duration, stone free rate, radiation dose and duration, irrigation fluid volume, post-operative hemoglobin drop and complications were compared. RESULTS: Demographic and stone characteristics were comparable in both groups. Supine Group (Group 1) had significantly shorter operative duration than Prone Group (Group 2), 44.63 ± 12.44minsvs 53.02 ±12.67mins (p< 0.04). The mean radiation duration was 99.11 ± 61.17secs in Group 1 and 108.40 ± 51.65 secs in Group 2 (p=0.46), respectively. Although the mean radiation dose was lower in Group 1 (375.1µGym2) than in Group 2 (465.7 µGym2), it was not statistically significant(p=0.24). The stone free rate at 1 month duration were comparable with 92.1% and 93.02% in Group 1 and Group 2 respectively (p=0.16). Overall complication rates were similar in both groups (15.7% in Group 1 vs 16.2% in Group 2), respectively. None of the patients in both groups had complications higher than Clavien IIIa. CONCLUSIONS: PCNL in supine position has significantly shorter operative time with similar complications and stone free rates as compared to prone position.

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.

Stone Clearance by Computed Tomography after Percutaneous Nephrolithotomy: A Descriptive Cross-sectional Study.

INTRODUCTION: Percutaneous nephrolithotomy has the highest stone free rate among other procedures with relatively higher complication rate. Post-operative imaging after stone surgeries has not been uniform. This study was done to study about the stone clearance by computed tomography after percutaneous nephrolithotomy. METHODS: The descriptive cross-sectional study was conducted in the Department of Urology, Bir Hospital for six months duration. The patients undergoing percutaneous nephrolithotomy and those with intra-operative fluoroscopic clearance were evaluated with a low dose computed tomography after 48 hours to assess residual fragments its size and location. Patient's demographics, stone characteristics and complications were compared between the stone free and with residual stone patients. RESULTS: Out of 72 percutaneous nephrolithotomy performed, 40 patients were included in the study. Low dose computed tomography kidney, ureter and bladder after 48 hours of surgery detected residual fragments in 11 (27.5%) patients. The RFs size of <4mm were found in 7 (63.63%) of cases whereas RFs of >4mm were found in 4 (36.36%). The stone size was 352.47 ± 97.47 mm2 and 254.79 ± 172.68mm2 in group with residual fragments and stone free group respectively. CONCLUSIONS: Low dose computed tomography kidney, ureter and bladder done for assessment of stone clearance after 48 hours of percutaneous nephrolithomy detected residual in around one fourth of patients, however majority of them had residual fragments <4mm. Intra-operative fluoroscopic clearance may over estimate stone clearance after percutaneous nephrolithomy as about one third of patients still may have residual fragments of >4mm size.

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 flexible hierarchical skew heavy-tailed multivariate meta regression models for individual patient data with applications.

A flexible class of multivariate meta-regression models are proposed for Individual Patient Data (IPD). The methodology is well motivated from 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. The research goal is to jointly analyze the multivariate outcomes, Low Density Lipoprotein Cholesterol (LDL-C), High Density Lipoprotein Cholesterol (HDL-C), and Triglycerides (TG). These three continuous outcome measures are correlated and shed much light on a subject's lipid status. The proposed multivariate meta-regression models allow for different skewness parameters and different degrees of freedom for the multivariate outcomes from different trials under a general class of skew t-distributions. The theoretical properties of the proposed models are examined and an efficient Markov chain Monte Carlo (MCMC) sampling algorithm is developed for carrying out Bayesian inference under the proposed multivariate meta-regression model. In addition, the Conditional Predictive Ordinates (CPOs) are computed via an efficient Monte Carlo method. Consequently, the logarithm of the pseudo marginal likelihood and Bayesian residuals are obtained for model comparison and assessment, respectively. A detailed analysis of the IPD meta data from the 26 Merck clinical trials is carried out to demonstrate the usefulness of the proposed methodology.

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.

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.

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.

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.

Tamsulosin versus tadalafil as a medical expulsive therapy for distal ureteral stones: A prospective randomized study.

PURPOSE: This study aimed to compare the safety and efficacy of tamsulosin and tadalafil as medical expulsive therapy for distal ureteral stones. MATERIALS AND METHODS: This prospective randomized study was conducted at the Department of Urology of Bir Hospital over a period of 12 months in patients with distal ureteral stones sized 5 to 10 mm. Patients were randomly divided into 2 groups: group A received tamsulosin 0.4 mg and group B received tadalafil 10 mg at bedtime for 2 weeks. Stone expulsion rate, number of ureteric colic episodes and pain score, analgesic requirements, and adverse drug effects were noted in both groups. Statistical analyses were performed by using Student t-test and chi-square test. RESULTS: Altogether 85 patients, 41 in group A and 44 in group B, were enrolled in the study. The patients' average age was 31.72±12.63 years, and the male-to-female ratio was 1.5:1. Demographic profiles, stone size, and baseline investigations were comparable between the 2 groups. The stone expulsion rate was significantly higher in the tadalafil group than in the tamsulosin group (84.1% vs. 61.0%, p=0.017). Although the occurrence of side effects was higher with tadalafil, this difference was not significant (p=0.099). There were no serious adverse effects. CONCLUSIONS: Tadalafil has a significantly higher stone expulsion rate than tamsulosin when used as a medical expulsive therapy for distal ureteral stones sized 5-10 mm. Both drugs are safe, effective, and well tolerated with minor side effects.

Inverse relationship between high-density lipoprotein cholesterol raising and high-sensitivity C-reactive protein reduction in older patients treated with lipid-lowering therapy.

BACKGROUND: Little is known regarding relationships between high-sensitivity C-reactive protein (hsCRP) and lipoproteins other than low-density lipoprotein cholesterol (LDL-C). High-density lipoprotein (HDL), with both anti-inflammatory and cholesterol-mediating effects, is of particular interest. This exploratory analysis assessed associations between hsCRP and lipids in older (>65 years) patients with moderate and/or high cardiovascular disease risk, before and after treatment with ezetimibe/simvastatin (E/S) or atorvastatin (ATV). METHODS: An analysis of a multicenter, randomized, double-blind, 12-week study. Correlations were assessed in 1054 patients with both baseline and 12-week hsCRP ≤ 10 mg/L, pooled across doses of E/S (10/20 and 10/40 mg) and ATV (10, 20, and 40 mg), and combined E/S + ATV treatments. Because of multiple comparisons, observed relationships were considered significant only if P values were < .01. RESULTS: Correlations between baseline levels of hsCRP and either LDL-C, non-HDL-C, or apolipoprotein B were weak and nonsignificant in the E/S, ATV, and E/S + ATV groups. After 12 weeks of treatment, these correlations increased slightly and significantly in all groups, except for LDL-C in the ATV group. HDL-C was significantly but inversely correlated with hsCRP in the ATV and E/S + ATV groups at baseline, and in all groups at 12 weeks. Only with HDL-C did change correlate with change in hsCRP in both the E/S and combined groups. CONCLUSIONS: Relationships between hsCRP and lipid factors in older patients were weak at baseline and somewhat stronger after treatment. HDL-C was inversely and consistently correlated with baseline and 12-week on-treatment hsCRP and with therapy-induced changes in HDL-C and hsCRP.

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-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.