Focal Segmental Glomerulosclerosis Patient Baseline Characteristics in the Sparsentan Phase 3 DUPLEX Study.

Introduction: The phase 3 DUPLEX trial is evaluating sparsentan, a novel, nonimmunosuppressive, single-molecule dual endothelin angiotensin receptor antagonist, in patients with focal segmental glomerulosclerosis (FSGS). Methods: DUPLEX (NCT03493685) is a global, multicenter, randomized, double-blind, parallel-group, active-controlled study evaluating the efficacy and safety of sparsentan 800 mg once daily versus irbesartan 300 mg once daily in patients aged 8 to 75 years (USA/UK) and 18 to 75 years (ex-USA/UK) weighing ≥20 kg with biopsy-proven FSGS or documented genetic mutation in a podocyte protein associated with FSGS, and urine protein-to-creatinine ratio (UP/C) ≥1.5 g/g. Baseline characteristics blinded to treatment allocation are reported descriptively. Results: The primary analysis population includes 371 patients (336 adult, 35 pediatric [<18 years]) who were randomized and received study drug (median age, 42 years). Patients were White (73.0%), Asian (13.2%), Black/African American (6.7%), or Other race (7.0%); and from North America (38.8%), Europe (36.1%), South America (12.7%), or Asia Pacific (12.4%). Baseline median UP/C was 3.0 g/g; 42.6% in nephrotic-range (UP/C >3.5 g/g [adults]; >2.0 g/g [pediatrics]). Patients were evenly distributed across estimated glomerular filtration rate (eGFR) categories corresponding to chronic kidney disease (CKD) stages 1 to 3b. Thirty-three patients (9.4% of 352 evaluable samples) had pathogenic or likely pathogenic (P/LP) variants of genes essential to podocyte structural integrity and function, 27 (7.7%) had P/LP collagen gene (COL4A3/4/5) variants, and 14 (4.0%) had high-risk APOL1 genotypes. Conclusions: Patient enrollment in DUPLEX, the largest interventional study in FSGS to date, will enable important characterization of the treatment effect of sparsentan in a geographically broad and clinically diverse FSGS population.

Therapeutic Phlebotomy in Patients with Grade 1 Hypertension: A Randomized-Controlled Trial.

Aim: Study aim was to investigate the effects of therapeutic phlebotomy on ambulatory blood pressure in patients with grade 1 hypertension. Methods: In this randomized-controlled intervention study, patients with unmedicated hypertension grade 1 were randomized into an intervention group (phlebotomy group; 500 mL bloodletting at baseline and after 6 weeks) and a control group (waiting list) and followed up for 8 weeks. Primary endpoint was the 24-h ambulatory mean arterial pressure between the intervention and control groups after 8 weeks. Secondary outcome parameters included ambulatory/resting systolic/diastolic blood pressure, heart rate, and selected laboratory parameters (e.g., hemoglobin, hematocrit, erythrocytes, and ferritin). Resting systolic/diastolic blood pressure/heart rate and blood count were also assessed at 6 weeks before the second phlebotomy to ensure safety. A per-protocol analysis was performed. Results: Fifty-three hypertension participants (56.7 ± 10.5 years) were included in the analysis (n = 25 intervention group, n = 28 control group). The ambulatory measured mean arterial pressure decreased by -1.12 ± 5.16 mmHg in the intervention group and increased by 0.43 ± 3.82 mmHg in the control group (between-group difference: -1.55 ± 4.46, p = 0.22). Hemoglobin, hematocrit, erythrocytes, and ferritin showed more pronounced reductions in the intervention group in comparison with the control group, with significant between-group differences. Subgroup analysis showed trends regarding the effects on different groups classified by serum ferritin concentration, body mass index, age, and sex. Two adverse events (AEs) (anemia and dizziness) occurred in association with the phlebotomy, but no serious AEs. Conclusions: Study results showed that therapeutic phlebotomy resulted in only minimal reductions of 24-h ambulatory blood pressure measurement values in patients with unmedicated grade 1 hypertension. Further high-quality clinical studies are warranted, as this finding contradicts the results of other studies.

Efficacy and Safety of Ozenoxacin Cream for Treatment of Adult and Pediatric Patients With Impetigo: A Randomized Clinical Trial.

Importance: Ozenoxacin, a novel topical antibacterial agent with potent bactericidal activity against gram-positive bacteria, has been developed as a cream with 1% active drug for the treatment of impetigo, a highly contagious bacterial skin infection. Objectives: To evaluate the efficacy, safety, and tolerability of ozenoxacin cream, 1%, after 5-day twice-daily topical treatment in patients with impetigo. Design, Setting, and Participants: This randomized, double-blind, vehicle-controlled clinical trial included patients 2 months or older with impetigo who were enrolled at centers in 6 countries from June 2, 2014, through May 30, 2015. Data were analyzed based on intention to treat from July 9 through July 22, 2015. Interventions: Patients were randomized 1:1 to receive topical ozenoxacin or placebo control. Main Outcomes and Measures: Efficacy was measured using the Skin Infection Rating Scale and microbiological culture. Safety and tolerability were also evaluated. Results: Among the 411 patients who received treatment (210 males [51.1%]; mean [SD] age, 18.6 [18.3] years), ozenoxacin demonstrated superior clinical success compared with placebo, which was evident after 5 days of therapy (112 of 206 [54.4%] vs 78 of 206 [37.9%]; P = .001). Ozenoxacin also demonstrated superior microbiological success compared with placebo after 2 days of therapy (109 of 125 [87.2%] vs 76 of 119 [63.9%]; P = .002). Ozenoxacin was well tolerated, with 8 of 206 patients experiencing adverse effects, with only 1 of these potentially related to the study treatment; none were serious. Conclusions and Relevance: Topical ozenoxacin is effective and well tolerated in the treatment of impetigo in patients 2 months and older. This effect is demonstrated by rapid onset of response and superior clinical and microbiological response compared with placebo. Topical ozenoxacin represents a novel option for the treatment of impetigo. Trial Registration: ClinicalTrials.gov Identifier: NCT02090764.

Clinical performance of an elastomeric lumbar disc replacement: Minimum 12 months follow-up.

BACKGROUND: Elastomeric disc replacements have been developed to restore normal shock absorption and physiologic centers of rotation to the degenerated disc. The Physio-L Artificial Lumbar Disc is an elastomeric disc which uses a compliant polycarbonate-polyurethane core with enhanced endurance properties. The objective of this study was to evaluate the safety and efficacy of the Physio-L through a 12-month follow-up period in a prospective, nonrandomized clinical trial. METHODS: Twelve patients who met the inclusion/exclusion criteria were enrolled in the study. Eight patients received a single implant (L5-S1) and 4 received a 2-level implantation (L4-5 and L5-S1). Patients were assessed preoperatively and postoperatively at 6 weeks and 3, 6, and 12 months. Primary outcomes included the VAS, ODI, a radiographic analysis of implant condition, incidence of major complications, and reoperations. Secondary outcomes included SF-36, ROM at index and adjacent levels and disc height. RESULTS: All patients completed the 12-month follow-up evaluations. Through 12 months, the Physio-L devices have remained intact with no evidence of subsidence, migration, or expulsion. VAS low-back pain and ODI scores improved significantly at all follow-up periods compared to preoperative scores. The range of motion of 13.3° ± 5.5° at the index level was considered normal. Overall, patients were satisfied with an average score of 83.5 ± 26.8 mm. When comparing the device to other artificial discs, the current device showed a clinically relevant improvement in both ODI and VAS scores at all follow-up time points. Statistically significant improvements in both scores were observed at 12 months (P < .05). CONCLUSION: The Physio-L is safe and efficacious, as demonstrated by improved pain relief and functional recovery without any implant failures, significant device related complications, or adverse incidents. The clinical results for VAS and ODI were superior to other marketed artificial lumbar discs such as the Charité and ProDisc-L at the same follow-up timeframes.

Randomized controlled comparison of two cognitive behavioral therapies for obese children: mother versus mother-child cognitive behavioral therapy.

BACKGROUND: Parent-child treatments have been shown to be superior to child-focused treatments of childhood obesity. Yet until now, the comparative effectiveness of parent-only and parent-child approaches has been little studied. METHOD: Fifty-six obese children and their families were randomly assigned to a 16-session cognitive behavioral therapy (CBT) for the parents only or for a combined treatment of parents and children. Children's percent overweight, the body mass index of their mothers, and behavioral and psychological problems of children and mothers were assessed. RESULTS: Both treatments reduced children's percent overweight significantly and equally by 6-month follow-up. Also both treatments provided similar results in reducing general behavior problems (externalizing and internalizing behavior problems), global and social anxiety, and depression. CONCLUSIONS: Our results point to a comparable efficacy of the two treatments. Further, psychological well-being of both mothers and children can be improved in a CBT for obese children and their parents. Future studies should focus on finding ways to improve the adherence of families to long-term treatment of obesity in childhood.

The effect of pre-vertebroplasty tumor ablation using laser-induced thermotherapy on biomechanical stability and cement fill in the metastatic spine.

A biomechanical study comparing simulated lytic vertebral metastases treated with laser-induced thermotherapy (LITT) and vertebroplasty versus vertebroplasty alone. To investigate the effect of tumor ablation using LITT prior to vertebroplasty on biomechanical stability and cement fill patterns in a standardized model of spinal metastatic disease. Vertebroplasty in the metastatic spine is aimed at reducing pain, but is associated with risk of cement extravasation in up to 10%. Six pairs of fresh-frozen cadaveric thoracolumbar spinal motion segments were tested in axial compression intact, with simulated metastases and following percutaneous vertebroplasty with or without LITT. Canal narrowing under load, pattern of cement fill, load to failure, and LITT temperature and pressure generation were collected. In all LITT specimens, cement filled the defect without extravasation. The canal extravasation rate was 33% in specimens treated without LITT. LITT and vertebroplasty yielded a trend toward improved posterior wall stability (P = 0.095) as compared to vertebroplasty alone. Moderate rises in temperature and minimal pressure generation was seen during LITT. In this model, elimination of tumor by LITT, facilitates cement fill, enhances biomechanical stability and reduces the risk of cement extravasation.

Load balance in total knee arthroplasty: an in vitro analysis.

BACKGROUND: One of the goals of total knee arthroplasty (TKA) is to balance the loads between the compartments of the knee. An instrumented load cell that measures compartment loads in real time is utilized to evaluate conventional, qualitative methods of achieving this balance. METHODS: TKA was performed on 10 cadaveric knees. Prior to and after load balancing, compartment forces were measured at flexion angles of 0-90 degrees. Knees were randomly assigned into one of two groups, based upon whether or not the surgeons could visualize the load cell's output during balancing. RESULTS: Prior to attempting load balance, there were significant differences between the medial and lateral compartment loads for all knees (p < 0.05). After attempting balance with the aid of the load cell, there was equal load balance at all angles studied. Without the aid of the load cell, balance was not consistently achieved at every angle. CONCLUSIONS: Conventional load balancing techniques in TKA are not perfect.

Biomechanical comparison of intramedullary nail and blade plate fixation for tibiotalocalcaneal arthrodesis.

OBJECTIVE: Tibiotalocalcaneal arthrodesis is used to manage severe bone loss, arthritis, and/or instability. The goal is to relieve pain through a stable, well-aligned hindfoot and ankle. The purpose of this study was 2-fold: to biomechanically compare 1) initial stability, and 2) the effect of bone density on the stability of intramedullary nail and blade plate fixation in tibiotalocalcaneal arthrodesis. DESIGN: Biomechanical study using anatomic specimens. METHODS: Ankle and subtalar joint capsules were exposed for 7 pairs of fresh-frozen anatomic specimens. One ankle from each pair was instrumented with an interlocked intramedullary nail inserted retrograde across the subtalar and ankle joint while the contralateral hind foot was stabilized with a lateral cannulated blade plate. Specimen stability was tested in plantar/dorsiflexion and inversion/eversion to a maximum bending moment of 12 Nm and in internal/external rotation to a maximum torque of 7 Nm. Physical measurements of bone density were made to determine its effect on stability. MAIN OUTCOME MEASURES: Maximum angular displacement of the constructs in plantarflexion, dorsiflexion, inversion, eversion, internal rotation, and external rotation. RESULTS: No significant differences were observed between the plated and nailed constructs in the 3 loading configurations (Power = 0.77). Only 6 pairs were included in the results because of fixation failures. A small but significant reduction in internal rotation alone of 1.8 degrees was found with the plated compared with the nailed construct (P = 0.045). Reduced stability was associated with lower bone density in torsion and inversion/eversion in the plated constructs (r = 0.67- 0.87) with a similar trend seen in torsion in the nailed constructs (r = 0.5). CONCLUSION: Initial construct stabilities and the effect of reduced bone density were found to be similar between the blade plate and the intramedullary nail in tibiotalocalcaneal arthrodesis, thus implant choice may be based on other clinical factors, such as surgeon preference or soft-tissue status.

Biomechanical stability of intramedullary nailed high proximal third tibial fractures with cement augmented proximal screws.

OBJECTIVE: Intramedullary nailing of nonarticular proximal tibia fractures can be affected by bone density resulting in loss of stability, fixation, and malalignment in osteopenic bone. This study was designed to quantify the biomechanical effects of augmenting proximal screws with cement in intramedullary nailing of high proximal third tibial fractures. DESIGN: In vitro biomechanical study using anatomic specimens. METHODS: Reamed nails were inserted into seven pairs of fresh-frozen cadaveric proximal tibiae and secured using two oblique and two transverse proximal screws. Paired tibiae were randomly assigned into two groups: cemented and noncemented proximal screw-holes. Bone cement was injected into the screw-holes before screw insertion in the cemented tibiae. Specimens were then tested in flexion/extension and varus/valgus to 12 Nm and in torsion to 7 Nm. Physical measurements of bone density were obtained to determine the effect of density on stability. MAIN OUTCOME MEASURES: Stability of the construct in both groups was analyzed and compared statistically using paired t tests. RESULTS: Cement augmentation of the proximal screws significantly increased mechanical stability in torsion and varus/valgus load configurations, with average decreases in rotational motion of 5.4 degrees +/- 1.6 degrees and 5.1 degrees +/- 5 degrees respectively. No change in stability was observed in flexion/extension loading. A trend toward decreased stability was seen in the uncemented construct in varus/valgus; cement augmentation of the proximal screws eliminated this effect. CONCLUSIONS: Lower bone density decreased the stability of the uncemented construct; however, cement augmentation of the proximal screws showed a trend to eliminate this effect in the varus/valgus loading configuration and should be considered when nailing proximal third tibial fractures in osteoporotic patients.

Biomechanical assessment of stability in the metastatic spine following percutaneous vertebroplasty: effects of cement distribution patterns and volume.

Percutaneous vertebroplasty is a minimally invasive, radiologically guided procedure whereby bone cement is injected into structurally weakened vertebrae to provide added biomechanical stability. In addition to treating osteoporotic vertebral fractures, this technique is also used to relieve pain by stabilizing metastatically compromised vertebrae that are at risk of pathologic burst fracture. Optimal cement distribution patterns to improve biomechanical stability to metastatically involved vertebral bodies remain unknown. This study aimed to determine the effect of cement location and volume of cement injected during percutaneous vertebroplasty on improving vertebral stability in a metastatically-compromised spinal motion segment using a parametric poroelastic finite element model. A three-dimensional parametric finite element model of a thoracic spinal motion segment was developed and analyzed using commercially available software. A total of 16 metastatic pre and post vertebroplasty scenarios were investigated using a serrated spherical representation of tumor tissue and various geometric representations of polymethylmethacrylate (PMMA). The effect of vertebroplasty on vertebral bulge, a measure of posterior vertebral body wall motion as an indicator of burst fracture initiation, was assessed. In all cases, vertebroplasty reduced vertebral bulge, but the risk of the initiation of burst fracture was minimized with cement located posterior to the tumor, near the posterior vertebral body wall. Vertebral bulge decreased by up to 62% with 20% cement injection. These findings demonstrate that location and distribution of cement within the vertebral body has a noticeable effect on the restoration of biomechanical stability following percutaneous vertebroplasty.

[Outpatient treatment of childhood and adolescent obesity]. / Ambulante Behandlung Adipositas im Kindes- und Jugendalter.

OBJECTIVES: Obesity in childhood is an increasing problem in both industrial and developing countries. Prevalence rates are up 15% in the U.S.A. and up 10% in Europe. The present paper gives an overview of current research on medical and psychosocial problems associated with childhood obesity. Treatment options are introduced and 24 studies are reviewed in detail with regard to treatment characteristics and outcome. METHODS: Medline and PsycINFO searches for outpatient treatment studies on childhood obesity between 1966 and 2003 were carried out. RESULTS: The limited comparability of the studies necessarily restricts their generalizability. CONCLUSIONS: Implications for the treatment of childhood obesity and further research are discussed.

Pressurization of the metastatic femur during prophylactic intramedullary nail fixation.

BACKGROUND: Venting during prophylactic nailing of metastatic femoral lesions may decrease intramedullary pressures and the risk of fat and tumor embolization. This study aimed to quantify maximum intramedullary pressure levels and durations, and to examine tumor displacement during prophylactic reamed intramedullary nailing of vented and nonvented metastatically involved femora. METHODS: Proximal metastatic defects were simulated in six pairs of cadaveric femora and prophylactically treated using reamed intramedullary nailing with or without proximal and distal vents. Maximum pressures, durations of pressure exceeding embolic threshold levels (25 and 200 mm Hg), and tumor displacement were recorded. RESULTS: Maximum pressures and durations of pressure exceeding embolic thresholds decreased more than 50% with venting (p < 0.05). Distal pressures surpassed the 25-mm Hg threshold even with venting. Post-test sectioning showed increased tumor disbursement in vented specimens. CONCLUSIONS: Venting reduces pressurization during prophylactic reamed intramedullary nailing of femoral metastases, but may increase the spread of tumor to extraskeletal tissue if vented tissue is not contained.

Metastatic burst fracture risk prediction using biomechanically based equations.

Clinical guidelines are a useful adjunct to select patients with spinal metastases for prophylactic intervention. The objective of this study is to determine the ability of biomechanically based models to accurately predict metastatic burst fracture risk. Ninety-two vertebrae with osteolytic spinal metastases were examined retrospectively. Vertebrae were categorized as burst fractured, wedge fractured, or intact and analyzed using three predictive models: vertebral bulge (maximum radial displacement under load), vertebral axial displacement (maximum axial displacement under load), and a volumetric estimate of tumor size. The load-bearing capacity parameter (tumor volume, bone mineral density, disc quality, pedicle involvement) was determined from computed tomography while the load-bearing requirement parameter (pressure load, loading rate) was determined using computed tomography and patient records (retrieved for 37 patients [52%]). Fracture prediction was optimized using the vertebral bulge model considering only load-bearing capacity with a specificity, sensitivity, and confidence interval of 1 to yield a clear threshold for burst fracture risk. Fracture prediction in the other two models, vertebral axial displacement considering only load-bearing capacity and tumor size, also was strong with receiver-operator curve values of 0.992 and 0.988, respectively. The predictive power of these models can provide useful clinical information for prophylactic decision-making.

Volumetric quantification of cement leakage following percutaneous vertebroplasty in metastatic and osteoporotic vertebrae.

OBJECT: The goal of this study was to quantify volumetrically cement fill and leakage in patients with osteoporotic and metastatic vertebral lesions undergoing percutaneous vertebroplasty and to establish whether these factors have any clinical significance at follow up. METHODS: Digital computerized tomography data were retrospectively collected from all cases at the authors' institution in which percutaneous vertebroplasty was performed for osteoporosis or metastatic disease. Patient selection was based on the consensus of a multidisciplinary team consisting of an orthopedic surgeon, an oncologist, and a neuroradiologist. A semiautomated thresholding technique was used to measure vertebral body volume, the volume of cement injected directly into the vertebra, and the volume of cement leakage. Pain-related scores were collected at four early stages of treatment, and all clinical complications were recorded. Cement leakage was found in 87.9% of vertebrae treated with percutaneous vertebroplasty. In osteoporotic vertebrae it occurred mainly in the disc, whereas in metastatic lesions, it was found in multiple areas. Irrespective of leakage, both patients with osteoporotic and metastatic disease experienced significant immediate pain relief postoperatively. CONCLUSIONS: Although there was no correlation between cement fill or cement leakage and pain relief, there exists a risk of serious complications due to cement leakage.

Contribution of ED admissions to inpatient hospital revenue.

Emergency department (ED) practices are traditionally profiled in terms of their patient encounters. Such evaluations reflect a preponderance of outpatient visits while crediting income from admitted patients to traditional hospital-based services. This study evaluates the contribution of ED admissions to inpatient hospital revenue. The study was set at an urban tertiary care community hospital with university affiliation. Information referable to ED patients was collected from the hospital's Universal Billing Code (UB-92)-based patient information warehouse. Data fields referable to hospital charges, insurance type, and disposition were used for analysis of a 1-year period from September 1, 1998 to August 31, 1999. Statistical analysis was through chi square and ANOVA. During the study period 33,174 patients were treated in the ED with 6,671 (20%) admitted to inpatient services. Total hospital charges for all ED patients during this time were $107 million dollars with $9.1 million (8.5%) generated from discharged patients and $98.0 million (91.5%) from admitted ED patients (P <.001). Mean charges for individual discharged patients were $344.10 whereas for individual admitted patients mean charges were $14,692.28. (P <.001) Medicaid and self pay represented 55.4% of the insurance coverage for discharged ED patients whereas these same insurance classes accounted for only 16.3% of admitted patients. (P <.001) Medicare visits accounted for 12.7% of discharged ED patients but 60.7% of admitted patients (P <.001). Total hospital gross revenue for inpatient services for the study period was $288 million of which 34% was contributed from admitted ED patients. ED services represent a major source of inpatient hospital revenue. The recognition of the ED's potential in this area may be lost if income from patients admitted through the ED is credited to traditional hospital-based services.

An anthropometric study of the distal ulna: implications for implant design.

Arthroplasty of the distal ulna is frequently used for distal radioulnar joint disorders; however, prosthetic failures are common. An implant replicating the ulna may be advantageous from the viewpoint of joint kinematics, wear, and fixation. The geometry of 40 distal ulnas was quantified by computed tomography scanning and radiography. Ulnar head diameter (16.8 +/- 1.6 mm), canal diameter (8.3 +/- 1.6 mm), eccentricity of the head relative to the shaft (2.5 +/- 1.4 mm), and angle of articulation (176 degrees +/- 29 degrees ) were measured. No correlation was found between the diameters of the ulnar head and intramedullary canal (R(2) = 0.2). A modular head-stem system with an eccentric offset may best reproduce the geometry of the distal ulna.