Army and Navy ECHO Pain Telementoring Improves Clinician Opioid Prescribing for Military Patients: an Observational Cohort Study.

BACKGROUND: Opioid overdose deaths occur in civilian and military populations and are the leading cause of accidental death in the USA. OBJECTIVE: To determine whether ECHO Pain telementoring regarding best practices in pain management and safe opioid prescribing yielded significant declines in opioid prescribing. DESIGN: A 4-year observational cohort study at military medical treatment facilities worldwide. PARTICIPANTS: Patients included 54.6% females and 46.4% males whose primary care clinicians (PCCs) opted to participate in ECHO Pain; the comparison group included 39.9% females and 60.1% males whose PCCs opted not to participate in ECHO Pain. INTERVENTION: PCCs attended 2-h weekly Chronic Pain and Opioid Management TeleECHO Clinic (ECHO Pain), which included pain and addiction didactics, case-based learning, and evidence-based recommendations. ECHO Pain sessions were offered 46 weeks per year. Attendance ranged from 1 to 3 sessions (47.7%), 4-19 (32.1%, or > 20 (20.2%). MAIN MEASURES: This study assessed whether clinician participation in Army and Navy Chronic Pain and Opioid Management TeleECHO Clinic (ECHO Pain) resulted in decreased prescription rates of opioid analgesics and co-prescribing of opioids and benzodiazepines. Measures included opioid prescriptions, morphine milligram equivalents (MME), and days of opioid and benzodiazepine co-prescribing per patient per year. KEY RESULTS: PCCs participating in ECHO Pain had greater percent declines than the comparison group in (a) annual opioid prescriptions per patient (- 23% vs. - 9%, P < 0.001), (b) average MME prescribed per patient/year (-28% vs. -7%, p < .02), (c) days of co-prescribed opioid and benzodiazepine per opioid user per year (-53% vs. -1%, p < .001), and (d) the number of opioid users (-20.2% vs. -8%, p < .001). Propensity scoring transformation-adjusted results were consistent with the opioid prescribing and MME results. CONCLUSIONS: Patients treated by PCCs who opted to participate in ECHO Pain had greater declines in opioid-related prescriptions than patients whose PCCs opted not to participate.

Progression of atherosclerosis versus arterial stiffness with age within and between arteries in systemic lupus erythematosus.

The progression of atherosclerosis versus arterial stiffness with age within and between arteries has not been defined. Systemic lupus erythematosus (SLE) is a human model of accelerated arterial disease that may permit this determination. 76 SLE patients (69 women, age 37 ± 12 years) and 26 age-and-sex-matched controls (22 women, age 34 ± 11 years) underwent transesophageal echocardiography and carotid ultrasonography for assessment of atherosclerosis [plaques and intima-media thickening (IMT)] and arterial stiffness [increased pressure-strain elastic modulus (PSEM)] of the descending thoracic aorta and carotid arteries. Since IMT is highly associated with plaques, IMT was used as a marker of atherosclerosis to assess its progression in relation with age and PSEM. Aortic and carotid plaques, IMT, and PSEM were greater in patients than in controls (all p ≤ 0.05). Within the aorta and within the carotid arteries, the average percent increases per decade of age for IMT versus PSEM were similar in patients (8.55% versus 9.33% and 3.39% versus 2.46%, respectively) and controls (5.53% versus 6.60% and 4.75% versus 3.49%, respectively) (all p ≥ 0.58). However, in SLE patients, the average percent increases per decade of age for IMT and PSEM were higher in the aorta than in the carotid arteries (8.55% and 9.33% versus 3.39% and 2.46%, respectively, both p ≤ 0.03). In patients with SLE, atherosclerosis and arterial stiffness progress with age parallel to each other within arteries, but divergently between arteries with different anatomy and hemodynamics.

ENDO ECHO IMPROVES PRIMARY CARE PROVIDER AND COMMUNITY HEALTH WORKER SELF-EFFICACY IN COMPLEX DIABETES MANAGEMENT IN MEDICALLY UNDERSERVED COMMUNITIES.

OBJECTIVE: To determine whether participation in a multidisciplinary telementorship model of healthcare delivery improves primary care provider (PCP) and community health worker (CHW) confidence in managing patients with complex diabetes in medically underserved regions. METHODS: We applied a well-established healthcare delivery model, Project ECHO (Extension for Community Healthcare Outcomes), to the management of complex diabetes (Endo ECHO) in medically underserved communities. A multidisciplinary team at Project ECHO connected with PCPs and CHWs at 10 health centers across New Mexico for weekly videoconferencing virtual clinics. Participating PCPs and CHWs presented de-identified patients and received best practice guidance and mentor-ship from Project ECHO specialists and network peers. A robust curriculum was developed around clinical practice guidelines and presented by weekly didactics over the ECHO network. After 2 years of participation in Endo ECHO, PCPs and CHWs completed self-efficacy surveys comparing confidence in complex diabetes management to baseline. RESULTS: PCPs and CHWs in rural New Mexico reported significant improvement in self-efficacy in all measures of complex diabetes management, including PCP ability to serve as a local resource for other healthcare providers seeking assistance in diabetes care. Overall self-efficacy improved by 130% in CHWs ( P<.0001) and by 60% in PCPs ( P<.0001), with an overall large Cohen's effect size. CONCLUSION: Among PCPs and CHWS in rural, medically underserved communities, participation in Endo ECHO for 2 years significantly improved confidence in complex diabetes management. Application of the ECHO model to complex diabetes care may be useful in resource-poor communities with limited access to diabetes specialist services. ABBREVIATIONS: CHW = community health worker; CME = Continuing Medical Education; ECHO = Extension for Community Healthcare Outcomes; FQHC = federally qualified health center; PCP = primary care provider.

Correlation of neurocognitive function and brain lesion load on magnetic resonance imaging in systemic lupus erythematosus.

Neurocognitive dysfunction and brain injury on magnetic resonance imaging (MRI) are common in patients with systemic lupus erythematosus (SLE) and are associated with increased morbidity and mortality. However, brain MRI is expensive, is restricted by payers, and requires high expertise. Neurocognitive assessment is an easily available, safe, and inexpensive clinical tool that may select patients needing brain MRI. In this cross-sectional and controlled study, 76 SLE patients (69 women, age 37 ± 12 years) and 26 age and gender-matched healthy subjects (22 women, age 34 ± 11 years) underwent assessment of attention, memory, processing speed, executive function, motor function, and global neurocognitive function. All subjects underwent brain MRI with T1-weighted, fluid-attenuated inversion recovery (FLAIR), and diffusion-weighted imaging. Hemispheric and whole brain lesion load in cm3 were determined using semi-automated methods. Neurocognitive z-scores in all clinical domains were significantly lower and whole brain and right and left hemispheres brain lesion load were significantly greater in patients than in controls (all p ≤ 0.02). There was significant correlation between neurocognitive z-scores in all domains and whole brain lesion load: processing speed (r = - 0.46; p < 0.0001), attention (r = - 0.42; p < 0.001), memory (r = - 0.40; p = 0.0004), executive function (r = - 0.25; p = 0.03), motor function (r = - 0.25; p = 0.05), and global neurocognitive function (r = - 0.38; p = 0.006). Similar correlations were found for brain hemisphere lesion loads (all p ≤ 0.05). These correlations were strengthened when adjusted for glucocorticoid therapy and SLE disease activity index. Finally, global neurocognitive z-score and erythrosedimentation rate were the only independent predictors of whole brain lesion load (both p ≤ 0.007). Neurocognitive measures and brain lesion load are worse in SLE patients than in controls. In SLE patients, neurocognitive z-scores correlate negatively with and independently predict brain lesion load. Therefore, neurocognitive testing may be an effective clinical tool to select patients needing brain MRI.

A model for conditional male trimorphisms.

Conditional dimorphisms are widespread in color, morphology, behavior, and life history. Such traits have been successfully modeled in game theory as conditional strategies, and in quantitative genetics as threshold traits. Conditional trimorphisms have recently been unveiled, and here we combine the rock-paper-scissors (RPS) model of game theory and the environmental threshold (ET) model of quantitative genetics to model trimorphisms that are environmentally induced and result from the expression of two thresholds. We investigated the tactic fitness structure for maintenance of alternative reproductive tactics in scarab dung beetles that constitute the first known examples of conditional male trimorphism. We parameterized a novel ternary fitness landscape that explains how conditional male trimorphism in these beetles can be maintained. We tracked changes in tactic frequencies in a wild population of Phanaeus triangularis and detected fitness intransitivity consistent with RPS dynamics. Quantitative predictions of our model compare favorably with corresponding observed parameters. The ternary landscape further reveals how geographic populations of these beetles can evolve between conditional trimorphism and dimorphism. The ternary model also suggests that polyphenic systems could potentially evolve between conditional and purely genetic mediation.

Distal tibia allograft for glenohumeral instability: does radius of curvature match?

BACKGROUND: A distal tibia osteochondral allograft is a potential graft option for glenoid reconstruction because the distal tibia may have a similar radius of curvature (ROC) as the glenoid. This study evaluated ROC mismatch as measured on computed tomography (CT) scans between the glenoid, distal tibia, and humeral head. METHODS: Bilateral CT images were formatted for 10 decedents from the Office of the Medical Investigator database, giving 20 specimens per anatomic location. The ROCs of the glenoid, distal tibia, and humeral head were measured. A statistical model was generated to assess ROC mismatch of randomly paired distal tibias and glenoids. RESULTS: The mean ± standard deviation ROC was 2.9 ± 0.25 cm for the glenoid, 2.3 ± 0.21 cm for the distal tibia, and 2.5 ± 0.12 cm for the humeral head. No differences were found in laterality, intraobserver, or interobserver measurements. The least-squares difference in the ROC between the glenoid and tibia was 0.57 cm, glenoid and humerus was 0.40 cm, and humerus and tibia was 0.17 cm. Only 22% of randomly paired distal tibias and glenoids had a difference in ROC of 0.3 cm or less. CONCLUSION: CT measurement of the ROC of the glenoid, distal tibia, and humeral head is reliable and reproducible. The probability of obtaining a random distal tibia allograft with a similar ROC to the glenoid is low. Obtaining ROC measurements of the injured glenoid and the distal tibia allograft specimen before use for glenoid reconstruction may be useful.

Cycling Versus Continuous Mode In Neuromodulator Programming: A Crossover, Randomized, Controlled Trial.

This is a randomized, controlled, blind, crossover trial comparing cycling versus continuous programming of a sacral neuromodulator in women diagnosed with overactive bladder (OAB). At 6 months, treatment order significantly affected Overactive Bladder Questionnaire - Short Form (OABq-SF) symptom scores. The cycling followed by continuous stimulation group had superior OABq-SF scores (p > 0.02).

Long-Term Blood-Brain Barrier Permeability Changes in Binswanger Disease.

BACKGROUND AND PURPOSE: The blood-brain barrier (BBB) is disrupted in small vessel disease patients with lacunes and white matter hyperintensities (WMHs). The relationship of WMHs and regional BBB permeability changes has not been studied. We hypothesized that BBB disruption occurs in normal appearing WM and regions near the WMHs. To test the hypothesis, we repeated BBB permeability measurements in patients with extensive WMHs related to Binswanger disease. METHODS: We selected a subset of 22 Binswanger disease subjects from a well-characterized larger prospective vascular cognitive impairment cohort. We used 16 age-matched controls for comparison. The abnormal WM permeability (WMP) was measured twice for several years using dynamic contrast-enhanced magnetic resonance imaging. WMP maps were constructed from voxels above a predetermined threshold. Scans from first and second visits were coregistered. WM was divided into 3 regions: normal appearing WM, WMH ring, and WMH core. The ring was defined as 2 mm on each side of the WMH border. WMP was calculated in each of the 3 specific regions. We used paired t test, ANOVA, and Fisher exact test to compare individual changes. RESULTS: WMP was significantly higher in subjects than in controls (P<0.001). There was no correlation between WMH load and WMP. High permeability regions had minimal overlap between first and second scans. Nine percent of WMP was within the WMHs, 49% within the normal appearing WM, and 52% within the WMH ring (P<0.001; ANOVA). CONCLUSIONS: Increased BBB permeability in normal appearing WM and close to the WMH borders supports a relationship between BBB disruption and the development of WMHs.

Reversible increase in maximal cortisol secretion rate in septic shock.

OBJECTIVE: Cortisol clearance is reduced in sepsis and may contribute to the development of impaired adrenocortical function that is thought to contribute to the pathophysiology of critical illness-related corticosteroid insufficiency. We sought to assess adrenocortical function using computer-assisted numerical modeling methodology to characterize and compare maximal cortisol secretion rate and free cortisol half-life in septic shock, sepsis, and healthy control subjects. DESIGN: Post hoc analysis of previously published total cortisol, free cortisol, corticosteroid-binding globulin, and albumin concentration data. SETTING: Single academic medical center. PATIENTS: Subjects included septic shock (n = 45), sepsis (n = 25), and healthy controls (n = 10). INTERVENTIONS: I.v. cosyntropin (250 µg). MEASUREMENTS AND MAIN RESULTS: Solutions for maximal cortisol secretion rate and free cortisol half-life were obtained by least squares solution of simultaneous, nonlinear differential equations that account for free cortisol appearance and elimination as well as reversible binding to corticosteroid-binding globulin and albumin. Maximal cortisol secretion rate was significantly greater in septic shock (0.83 nM/s [0.44, 1.58 nM/s] reported as median [lower quartile, upper quartile]) compared with sepsis (0.51 nM/s [0.36, 0.62 nM/s]; p = 0.007) and controls (0.49 nM/s [0.42, 0.62 nM/s]; p = 0.04). The variance of maximal cortisol secretion rate in septic shock was also greater than that of sepsis or control groups (F test, p < 0.001). Free cortisol half-life was significantly increased in septic shock (4.6 min [2.2, 6.3 min]) and sepsis (3.0 min [2.3, 4.8 min] when compared with controls (2.0 min [1.2, 2.6 min]) (both p < 0.004). CONCLUSIONS: Results obtained by numerical modeling are consistent with comparable measures obtained by the gold standard stable isotope dilution method. Septic shock is associated with generally not only higher levels but also greater variance of maximal cortisol secretion rate when compared with control and sepsis groups. Additional studies would be needed to determine whether assessment of cortisol kinetic parameters such as maximal cortisol secretion rate and free cortisol half-life is useful in the diagnosis or management of critical illness-related corticosteroid insufficiency.

Lambl's Excrescences: Association with Cerebrovascular Disease and Pathogenesis.

BACKGROUND: Lambl's excrescences (LEx) are detected by transesophageal echocardiography (TEE) and are characterized as thin, elongated, and hypermobile structures located at the leaflets' coaptation point of the heart valves. The association of LEx with cerebrovascular disease (CVD) is still undefined and yet patients with LEx and suspected CVD receive unproven effective antiplatelet or anticoagulant therapy or even undergo valve surgery. Also, the association of LEx with aging and atherogenic, inflammatory, or thrombogenic parameters has not been reported. METHODS: Seventy-seven patients with systemic lupus erythematosus (SLE) (71 women, age 37 ± 12 years) and 26 age- and sex-matched healthy controls (22 women, age 34 ± 11 years) prospectively underwent routine history and physical exam, transcranial Doppler, brain MRI, TEE, carotid duplex, and clinical and laboratory evaluations of atherogenesis, inflammation, platelet activity, coagulation, and fibrinolysis. Subjects without stroke/TIA on enrollment (with and without LEx) had a median follow-up of 57 months. RESULTS: On enrollment, 33 (43%) of 77 patients had CVD manifested as acute stroke/TIA (23 patients), cerebromicroembolism by transcranial Doppler (17 patients), or cerebral infarcts by MRI (14 patients). Mitral or aortic valve LEx were equally frequent in healthy controls (46%) as in patients with and without any CVD (39 and 43%), stroke/TIA (35 and 43%), cerebromicroembolism (41 and 42%), or cerebral infarcts (36 and 43%) (all p ≥ 0.72). Also, other mechanisms for CVD other than LEx such as Libman-Sacks vegetations, patent foramen ovale or interatrial septal aneurysm, aortic or carotid atherosclerosis, or thrombogenesis were found in ≥94% of patients with CVD. In addition, 36 subjects with and 44 without LEx had similar low incidence of stroke/TIA (1 (1.3%) and 2 (2.5%), respectively, p = 1.0) during follow-up. Finally, LEx were not associated with aging, atherogenic risk factors, atherosclerosis, inflammation, or thrombogenesis. CONCLUSIONS: In this study, LEx are similarly prevalent in healthy controls and SLE patients, are not associated with CVD, and are not associated with pathogenic risk factors. Therefore, the study findings suggest that LEx may not be cardioembolic substrates, may not represent pathologic valve structures, and may not require therapy.

Risk factors for lower urinary tract injury at the time of hysterectomy for benign reasons.

OBJECTIVES: To identify risk factors associated with lower urinary tract injury at the time of performing hysterectomy for benign indications. METHODS: We conducted a multi-center case-control study of women undergoing hysterectomy for benign disease. Cases were identified via ICD-9 codes for lower urinary tract injury at the time of hysterectomy from 2007 to 2011: controls were two subsequent hysterectomies following the index case in the same institution that did not have lower urinary tract injury. Logistic regression was used to perform univariate and multivariate comparisons between groups. RESULTS: At 7 centers, 135 cases and 270 controls were identified. Cases comprised 118 bladder injuries and 25 ureteral injuries; 8 women had both bladder and ureteral injury. Bladder injury was associated with a history of prior cesarean section OR 2.9 (95% CI 1.7-5), surgery by a general obstetrician and gynecologist OR 2.4 (95% CI 1.2-5.2), and total abdominal hysterectomy OR1.9 (95%CI 1.06-3.4). Ureteral injury was more likely among women who underwent laparoscopic-assisted vaginal hysterectomy (LAVH) OR 10.4 (95%CI 2.3-46.6) and total abdominal hysterectomy (TAH) OR 4.7 (95% CI 1.4-15.6). CONCLUSION: Bladder injury at the time of benign hysterectomy is associated with a prior history of Cesarean section and TAH as well as surgery by generalist OB-GYN; ureteral injury is associated with LAVH and TAH.

Goal attainment after treatment in patients with symptomatic pelvic organ prolapse.

OBJECTIVE: The objectives of this study were to: (1) assess differences in goal attainment of self-described goals after treatment of symptomatic pelvic organ prolapse (POP) for women who chose surgery compared to women who chose pessary; and (2) compare patient global improvement between groups. STUDY DESIGN: Women who had symptomatic stage ≥II prolapse presenting for care of POP to the urogynecology clinic at the University of New Mexico were recruited. Patients listed up to 3 goals they had for their treatment. In addition, they completed the short forms of the Pelvic Floor Distress Inventory (PFDI-20), the POP/Urinary Incontinence Sexual Questionnaire, and the Body Image Scale. Goals listed by patients were then categorized into 10 categories. Each of the listed goals was categorized based on a consensus of 5 providers. At 3 months' follow-up patients listed if they had met their self-described goals on a scale of 0-10 and also answered the Patient Global Improvement Index (PGI-I). RESULTS: There were no significant differences between the 2 groups' baseline characteristics. Surgery patients ranked their goal attainment higher than pessary patients for all the 3 goals listed. Similarly, PGI-I scores were also higher in the surgical (2.4 ± 1.1) than the pessary (1.93 ± 0.8) treatment groups (P < .04). Patients in the surgery group also had better symptom improvement as measured by the PFDI-20 (P < .02). CONCLUSION: Patients who chose surgery had better global improvement and met their goals better compared to patients who chose pessary.

High serum levels of free cortisol indicate severity of cirrhosis in hemodynamically stable patients.

BACKGROUND AND AIM: We investigated: (i) the association between severity of cirrhosis and serum levels of free cortisol (SFC) and total cortisol (STC), measured before and 30 min after (T(30)) the low-dose 1-µg short synacthen test (LD-SST); and (ii) the prognostic value of SFC and STC. METHODS: Consecutive, hemodynamically stable, cirrhotic patients (34 Child-Pugh class A, 29B, and 32C) underwent the LD-SST. Patients were followed for at least 12 months to assess non-transplant-related mortality. RESULTS: Child-Pugh class C patients had significantly higher basal levels of SFC than Child-Pugh class A or B patients. Prevalence of suspected adrenal dysfunction ranged between 7.4% (T(0) STC < 138 nmol/L) and 49.4% (change in STC < 250 nmol/L) according to the threshold used. In receiver-operator curve analysis, the area-under-the-curve values were 0.67 for T(30) SFC (0.51-0.79), 0.81 for Child-Pugh score (0.70-0.88), and 0.79 for albumin level (0.63-0.88). During the follow-up period, 16 patients with high T(30) SFC (≥ 78.9 nmol/L) (26.2%) and one patient with low T(30) SFC (< 78.9 nmol/L) (3.4%) died (P = 0.027 for high vs low T(30) SFC, log-rank test). Albeit not statistically significant, the risk of death for patients with T(30) SFC ≥ 78.9 nmol/L was fivefold higher than for patients with lower levels after adjusting for cirrhosis severity and level of albumin. CONCLUSIONS: One-year, non-transplant-related mortality is high among patients with T(30) levels of SFC ≥ 78.9 nmol/L (26.2%). These findings might result from latent inflammatory stress in hemodynamically stable cirrhotic patients, detected by adrenal testing.

Four-Compartment Diffusion Model of Cortisol Disposition: Comparison With 3 Alternative Models in Current Clinical Use.

Context: Estimated rates of cortisol elimination and appearance vary according to the model used to obtain them. Generalizability of current models of cortisol disposition in healthy humans is limited. Objective: Development and validation of a realistic, mechanistic model of cortisol disposition that accounts for the major factors influencing plasma cortisol concentrations in vivo (Model 4), and comparison to previously described models of cortisol disposition in current clinical use (Models 1-3). Methods: The 4 models were independently applied to cortisol concentration data obtained for the hydrocortisone bolus experiment (20 mg) in 2 clinical groups: healthy volunteers (HVs, n = 6) and corticosteroid binding globulin (CBG)-deficient (n = 2). Model 4 used Fick's first law of diffusion to model free cortisol flux between vascular and extravascular compartments. Pharmacokinetic parameter solutions for Models 1-4 were optimized by numerical methods, and model-specific parameter solutions were compared by repeated measures analysis of variance. Models and respective parameter solutions were compared by mathematical and simulation analyses, and an assessment tool was used to compare performance characteristics of the four models evaluated herein. Results: Cortisol half-lives differed significantly between models (all P < .001) with significant model-group interaction (P = .02). In comparative analysis, Model 4 solutions yielded significantly reduced free cortisol half-life, improved fit to experimental data (both P < .01), and superior model performance. Conclusion: The proposed 4-compartment diffusion model (Model 4) is consistent with relevant experimental observations and met the greatest number of empiric validation criteria. Cortisol half-life solutions obtained using Model 4 were generalizable between HV and CBG-deficient groups and bolus and continuous modes of hydrocortisone infusion.

Risk factors for poor prognosis in microinvasive adenocarcinoma of the uterine cervix (IA1 and IA2): a pooled analysis.

OBJECTIVE: To identify adverse risk factors for FIGO IA1 and IA2 cervical adenocarcinoma. METHODS: PubMed was used to identify all microinvasive adenocarcinoma cases. Case specific data pooled for 35 "high risk" microinvasive adenocarcinoma (MIAC), defined as cases with lymph node or lymphovascular space involvement, positive surgical margins, or recurrence was compared with 478 "low risk" cases abstracted from the SEER database (1988-1997). Statistical methods included non-paired t and Fisher's Exact tests. RESULTS: Survival for 1A1 and 1A2 MIAC is 99% and 98%, respectively. Significantly more 1A2 patients underwent aggressive radical surgery and received postoperative treatment. Parametrial involvement was rare (1/373 cases). Significantly more "high-risk" cases were of endometrioid histology (6/34 vs. 14/478, p=0.001), whereas adenocarcinoma (p=0.046) and mucinous (p=0.021) tumors were observed in the "low-risk" group. Among the "high-risk" cases with at least 5 years follow-up, 1.4% has recurred or died. CONCLUSIONS: Endometrioid histology may be associated with late recurrence and worse survival in stage 1A1 and 1A2 MIAC.

Prevalence and Treatment of Postpartum Stress Urinary Incontinence: A Systematic Review.

OBJECTIVES: Many women present for treatment of stress urinary incontinence (SUI) after childbirth. This systematic review describes the efficacy of treatment options for SUI initiated during the 12 months after delivery. METHODS: We conducted a systematic review to identify studies comparing treatment options for SUI initiated in the 12 months after parturition. We searched MEDLINE from inception to February 2019, using Medical Subject Heading terms related to pregnancy and urinary incontinence. Preintervention and postintervention populations were compared using analysis of variance with Fisher least significant difference method used to determine efficacy between groups. Grades for Recommendation, Assessment, Development and Evaluation system was used to categorize quality of evidence as high, moderate, low, or very low. RESULTS: We double screened 4548 abstracts, identifying 98 articles for full-text review. Seven studies met the eligibility criteria and were included. Compared with a control group, the 4 interventions identified outperformed the control group (P < 0.001) using Fisher (with effect sizes noted): (1) supervised pelvic floor physical therapy (0.76), (2) electrical stimulation (0.77), (3) home physical therapy (PT) (0.44), and (4) surgery (not applicable). Based on Grades for Recommendation, Assessment, Development and Evaluation assessment, there was moderate evidence to support PT and electrical stimulation, with insufficient evidence for surgery. There were no significant differences in parity, age, or body mass index via analysis of variance. The overall strength of evidence is poor for the treatment of postpartum SUI; more data are needed to fully evaluate other treatment options. CONCLUSIONS: All identified interventions demonstrated greater improvement for postpartum SUI over no treatment. Supervised PT ± electrostimulation was the most effective nonsurgical intervention.

Libman-Sacks endocarditis and associated cerebrovascular disease: The role of medical therapy.

BACKGROUND: Libman-Sacks endocarditis in patients with systemic lupus erythematosus (SLE) is commonly complicated with embolic cerebrovascular disease (CVD) or valve dysfunction for which high-risk valve surgery is frequently performed. However, the role of medical therapy alone for Libman-Sacks endocarditis and associated acute CVD remains undefined. OBJECTIVE: To determine in this cross-sectional and longitudinal study if conventional anti-inflammatory and anti-thrombotic therapy may be an effective therapy in SLE patients with Libman-Sacks endocarditis and associated acute CVD. METHODS AND MATERIALS: 17 SLE patients with Libman-Sacks endocarditis detected by two-and-three-dimensional transesophageal echocardiography (TEE) and complicated with acute CVD [stroke/TIA, focal brain injury on MRI, or cognitive dysfunction] were treated with conventional anti-inflammatory and anti-thrombotic therapy for a median of 6 months and then underwent repeat TEE, transcranial Doppler, brain MRI, and neurocognitive testing for re-assessment of Libman-Sacks endocarditis and CVD. RESULTS: Valve vegetations decreased in number, diameter, and area (all p ≤0.01); associated valve regurgitation significantly improved (p = 0.04), and valve thickening did not progress (p = 0.56). In 13 (76%) patients, valve vegetations or valve regurgitation resolved or improved in number and size or by ≥1 degree, respectively, as compared to 4 (24%) patients in whom vegetations or valve regurgitation persisted unchanged or increased in size or by ≥1 degree (p = 0.03). Also, cerebromicroembolism, lobar and global gray and white matter cerebral perfusion, ischemic brain lesion load, and neurocognitive dysfunction resolved or significantly improved (all p ≤0.04). CONCLUSION: These preliminary data suggest that combined conventional anti-inflammatory and antithrombotic therapy may be an effective treatment for Libman-Sacks endocarditis and its associated CVD and may obviate the need for high-risk valve surgery.

Aortic adventitial thickness as a marker of aortic atherosclerosis, vascular stiffness, and vessel remodeling in systemic lupus erythematosus.

INTRODUCTION: There is limited human imaging data on the association of adventitial thickness (AT) with arterial disease. Systemic lupus erythematosus (SLE) is a prototypical disease model for studying markers of premature arterial disease. OBJECTIVE: To determine if increased aortic AT is associated with aortic atherosclerosis [increased intima media thickness (IMT) or plaques], stiffness [increased pressure-strain elastic modulus (PSEM)], and vessel remodeling. METHODS: In total, 70 SLE patients and 26 age- and sex-matched controls underwent transesophageal echocardiography (TEE). Two-dimensional guided M-mode images were obtained to assess AT, IMT, and plaques, and PSEM at the proximal, mid, and distal thoracic aorta. Images were interpreted by 3 observers unaware of the subjects' clinical data and each other's measurements. Abnormal aortic AT, IMT, and PSEM were defined as > 2SD above the overall mean values in controls and corresponded to > 1 mm, > 1 mm, and > 10.6 Pascal units, respectively. Plaques were defined as focal-protruding IMT > 50% of the surrounding vessel wall. RESULTS: Abnormal aortic AT, atherosclerosis, and abnormal stiffness were more frequent in SLE patients than in controls (all p ≤ 0.02). In SLE patients, abnormal AT combined with atherosclerosis was associated with larger aortic end-diastolic diameters than in controls (p ≤ 0.05). In SLE patients, aortic AT was greater in patients with atherosclerosis and in those with abnormal stiffness than in patients without these abnormalities (all p ≤ 0.02). In patients with abnormal AT, the degree of aortic stiffness was similar to those with atherosclerosis (p = 0.22). CONCLUSION: In patients with SLE, increased aortic AT is associated with aortic atherosclerosis, abnormal stiffness, and eccentric vessel remodeling. Key Points • In patients with SLE, abnormal aortic adventitial thickness is associated with aortic atherosclerosis, abnormal stiffness, and eccentric vessel remodeling. • In patients with SLE, aortic adventitial thickening may contribute to the extent of aortic atherosclerosis, abnormal aortic stiffness, and vessel remodeling. • To our knowledge, this is the first human imaging study to characterize the aortic adventitial layer and delineate its association with aortic disease.

Decreased maximal cortisol secretion rate in patients with cirrhosis: Relation to disease severity.

BACKGROUND & AIMS: Hepatic enzymes play a major role in the metabolic elimination of cortisol, and reduced rates of cortisol clearance have been consistently observed in patients with chronic liver disease. It is less clear whether there are concomitant abnormalities of adrenocortical function in patients with cirrhosis. In the present study, we sought to assess adrenocortical function in patients with cirrhosis using measures of free cortisol appearance and elimination rates that are independent of serum concentrations of cortisol binding proteins. METHODS: Post hoc analysis used computer-assisted numerical and modelling methods with serial total and free cortisol concentration data to obtain rates of free cortisol appearance and elimination. Rate parameters were obtained in 114 patients with chronic liver disease, including Child-Pugh (CP) ≤8 (n = 53) and CP >8 (n = 61). RESULTS: Maximal cortisol secretion rate (CSRmax) was significantly decreased (p = 0.01) in patients with cirrhosis with CP >8 (0.28 nM/s; 95% CI 0.24-0.34) compared with those with CP ≤8 (0.39 nM/s; 95% CI 0.33-0.46), and CSRmax was negatively correlated with CP score (r = -0.19, p = 0.01). Free cortisol elimination rate was significantly (p = 0.04) decreased in the CP >8 group (0.16 ± 0.20 min-1) compared with that in the CP ≤8 group (0.21 ± 0.21 min-1), and free cortisol elimination rates were negatively correlated with CP score (r = -0.23, p = 0.01). A significant correlation between CSRmax and free cortisol elimination rate (r = 0.88, p <0.001) was observed. CONCLUSIONS: CSRmax and free cortisol elimination rates were significantly reduced according to severity of cirrhosis. In contrast to stimulated total cortisol concentrations, CSRmax estimates were independent of cortisol-binding protein concentrations. Results provide additional evidence of subnormal adrenocortical function in patients with cirrhosis. LAY SUMMARY: We applied numerical analytic methods to characterise adrenocortical function in patients with varying stages of chronic liver disease. We found that patients with more severe cirrhosis have decreased rate of free cortisol elimination and decreased maximal cortisol secretion rate, which is a measure of adrenocortical function. In contrast to conventional measures of adrenocortical function, those obtained using numerical methods were not affected by variation in corticosteroid binding globulin and albumin concentrations. We conclude that patients with cirrhosis demonstrate measurable abnormalities of adrenocortical function, evidence of which supports aspects of the hepatoadrenal syndrome hypothesis.

Reduced FcepsilonRI-mediated release of asthma-promoting cytokines and chemokines from human basophils during omalizumab therapy.

BACKGROUND: Treating asthmatics with the humanized IgE-scavenging antibody, omalizumab (rhuMAb-E25, Xolair, reduces airways inflammation and asthma symptoms. Previously, omalizumab was shown to cause a dramatic and reversible loss of cell surface high-affinity IgE receptors, FcepsilonRI, from the peripheral blood basophils of asthmatics. The consequences of receptor loss for the FcepsilonRI-mediated synthesis and release of cytokines implicated in allergic asthma have not been examined. METHODS: Fifteen asthmatic volunteers each received omalizumab for 12 weeks. Peripheral blood basophils were isolated before, during, 2 weeks after and 6 months after omalizumab. Basophils were assayed for the basal and anti-IgE-stimulated release of cytokines, chemokines and histamine. Pooled data were analyzed by repeated measures ANOVA and by paired t tests. RESULTS: Anti-IgE-stimulated human basophils synthesize and release Th2 cytokines (IL-4, IL-13) and chemokines (IL-8, RANTES). The anti-IgE-stimulated release of IL-4, IL-13 and IL-8 was reduced during omalizumab treatment and returned to pretreatment levels after omalizumab withdrawal. Omalizumab did not alter basophil histamine levels or basal and anti-IgE-stimulated histamine release. CONCLUSIONS: Omalizumab may reduce asthma symptoms in part by suppressing the FcepsilonRI-mediated production by basophils of Th2 cytokines and selected chemokines. Anti-IgE-stimulated basophil cytokine synthesis appears more sensitive than histamine release to the loss of FcepsilonRI caused by omalizumab treatment.