Extracorporeal Shockwave Therapy for Greater Trochanteric Pain Syndrome: A Systematic Review with Meta-Analysis of Randomized Clinical Trials.

BACKGROUND: Greater trochanteric pain syndrome (GTPS) affects 17.6% of adults aged 50 to 79 years, particularly women. While exercise therapy and corticosteroid injections (CSIs) are common treatments, their limitations include inadequate pain control and potential tendon weakening. Extracorporeal shockwave therapy (ESWT) is an emerging alternative for GTPS. This systematic review assessed ESWT's efficacy in GTPS by evaluating pain and functional outcomes at different follow-up intervals. METHODS: A literature search of PubMed, Embase, and Web of Science for randomized clinical trials (RCTs) was conducted comparing ESWT with other GTPS treatments up to March 1, 2024. Two reviewers independently extracted data, assessing study quality using the Cochrane risk-of-bias tool. A random-effects pairwise meta-analysis compared ESWT with other treatments. RESULTS: Eight RCTs involving 754 patients (169 male, 585 female patients) were included. Seven RCTs were deemed high risk of bias, and 1 RCT had some concerns. Five RCTs investigated focused on focused ESWT, and 3 examined radial ESWT. ESWT provided significantly lower pain scores than other treatments at 2 to 4 months (standardized mean difference = -0.431; 95% confidence interval [CI], -0.82 to -0.039; I2 = 83%). Functional improvement (Lower Extremity Functional Scale) was significantly higher at 6 months (weighted mean difference = 6.68; 95% CI, 3.11-10.25; I2 = 0%) but did not exceed the minimal clinically important difference. Focused ESWT provided greater pain reduction than radial ESWT. CONCLUSION: Three weekly ESWT sessions offer short-term pain relief at 2 to 4 months for patients with GTPS, especially with focused ESWT. Functional improvements at 6 months were notable but not clinically significant. These findings suggest ESWT may complement or serve as an alternative to CSIs and exercise. However, caution is needed when interpreting these results due to high risk of bias with the included RCTs and heterogeneity across the studies. Further high-quality trials are needed to confirm ESWT's long-term benefits over other treatments. LEVEL OF EVIDENCE: Level II. See Instructions for Authors for a complete description of levels of evidence.

Epidemiology of injuries in united states high school track and field jumping events from 2008 - 2019.

OBJECTIVES: Reports of injury characteristics of high school track and field athletes participating in jumping events in the United States are limited. In this descriptive epidemiological study, we report injury rates and patterns in these athletes. METHODS: Injuries and athletic exposures (AE) from the National High School Sports Related Injury Surveillance System, and High School Reporting Information Online (RIO) from 2008-2019 were analyzed. Jumping events included high jump, long jump, triple jump, and pole vault. Injury rate ratios (IRR) and injury proportion ratios (IPR) were examined by sex. RESULTS: A total of 727 injuries related to jumping events during 5,486,279 AEs occurred with the highest frequency at the thigh (20.3%) followed by the ankle (18.2%), knee (16.1%), and lower leg (11.0%). The most common types of injuries were muscle strain (29.0%) and ligament sprain (21.2%). Most athletes returned to sport within 1 week (43.1%, n = 312) or 3 weeks (34.7%, n = 243). Few jumping-related injuries resulted in surgery (4.9%, n = 35) or medical disqualification (4.4%, n = 31). The jumping-related injury rate was 1.33 injuries/10,000 AEs from 2008 to 2019. The rate of jumping-related injuries was higher in competition than in practice (IRR = 2.63, 95% confidence interval [CI]: 2.25-3.06). Injury rates were significantly higher in practice for female athletes than for males (IRR = 1.51, 95% CI: 1.23-1.86). Compared to male athletes, female athletes sustained a higher proportion of ankle injuries (IPR = 1.63, 95% CI: 1.15-2.32) and ligament sprains (IPR = 1.55, 95% CI: 1.16-2.09). CONCLUSIONS: This study describes injury characteristics of high school track and field jumping athletes from 2008 to 2019. We found an overall injury rate of 1.33 injuries per 10,000 AEs. Higher overall rates of jumping-related injuries occurred during competitions than in practice, and female athletes displayed a significantly higher rate of injuries during practices compared to male athletes.

Nonsteroidal Anti-Inflammatory Drug Injections versus Steroid Injections in the Management of Upper and Lower Extremity Orthopedic Conditions: A Systematic Review with Meta-Analysis.

BACKGROUND: Although corticosteroid injections are an effective treatment for musculoskeletal pathologies, they may not be suitable for all patients. The purpose of this systematic review was to compare clinical outcomes between patients who received NSAID and corticosteroid injections for various orthopedic conditions. METHODS: Medline, Embase, Web of Science, and Cochrane Central Register of Controlled Trials were searched, and meta-analyses were performed using a random-effects model for outcomes presented in three or more studies. Other studies were qualitatively analyzed. RESULTS: A total of 28 articles with 2113 patients were included. A meta-analysis of five studies in patients with shoulder impingement syndrome demonstrated that there was no significant difference in the pain visual analogue scale (VAS) between subacromial NSAID injections and corticosteroid injections at 1 month [weighted mean difference (WMD) -0.244; 95% CI, -1.232 to 0.745; I2, 94.5%]. For patients with knee osteoarthritis, a meta-analysis of three studies demonstrated that there was no significant difference between intraarticular NSAID injections and corticosteroid injections in pain VAS at 1 month (WMD 0.754; 95% CI, -0.413 to 1.921; I2, 90.2%) and 3 months (WMD-0.089; 95% CI, -0.345 to 0.166; I2, 0%). A review of the studies assessing pain outcomes for hip osteoarthritis, adhesive capsulitis, and plantar fasciitis showed no significant differences between the NSAID and corticosteroid groups. CONCLUSION: NSAID injections may be safe and effective alternatives to steroid injections, especially in shoulder impingement syndrome and knee osteoarthritis.

Study Protocol STEREOLAB: Stereotactic Liver Ablation Assisted with Intra-Arterial CT Hepatic Arteriography and Ablation Confirmation Software Assessment.

PURPOSE: This study aims to evaluate the technical efficacy and local tumor progression-free survival (LTPFS) of a standardized workflow for thermal ablation of colorectal liver metastases (CRLM) consisting of CT during hepatic arteriography (CTHA)-based imaging analysis, stereotactic thermal ablation, and computer-based software assessment of ablation margins. MATERIALS AND METHODS: This investigator initiated, single-center, single-arm prospective trial will enroll up to 50 patients (≤ 5 CRLM, Measuring ≤ 5 cm). Procedures will be performed in an angio-CT suite under general anesthesia. The primary objective is to estimate LTPFS with a follow-up of up to 2 years and secondary objectives are analysis of the impact of minimal ablative margins on LTPFS, adverse events, contrast media utilization and radiation exposure, overall oncological outcomes, and anesthesia/procedural time. Adverse events (AE) will be recorded by CTCAE (Common Toxicity Criteria for Adverse Events), and Bayesian optimal phase-2 design will be applied for major intraprocedural AE stop boundaries. The institutional CRLM ablation registry will be used as benchmark for comparative analysis with the historical cohort. DISCUSSION: The STEREOLAB trial will introduce a high-precision and standardized thermal ablation workflow for CRLM consisting of CT during hepatic arteriography imaging, stereotactic guidance, and ablation confirmation. Trial Registration ClinicalTrials.gov identifier: (NCT05361551).

Aldosterone Contributes to Vasopressin Escape through Changes in Water and Urea Transport.

Hyponatremia (hypo-osmolality) is a disorder of water homeostasis due to abnormal renal diluting capacity. The body limits the degree to which serum sodium concentration falls through a mechanism called "vasopressin escape". Vasopressin escape is a process that prevents the continuous decrease in serum sodium concentration even under conditions of sustained high plasma vasopressin levels. Previous reports suggest that aldosterone may be involved in the vasopressin escape mechanism. The abilities of aldosterone synthase (Cyp11b2) knockout and wild-type mice to escape from vasopressin were compared. Wild-type mice escaped while the aldosterone synthase knockout mice did not. Both the water channel aquaporin 2 (AQP2) and the urea transporter UT-A1 protein abundances were higher in aldosterone synthase knockout than in wild-type mice at the end of the escape period. Vasopressin escape was also blunted in rats given spironolactone, a mineralocorticoid receptor blocker. Next, the role of the phosphatase, calcineurin (protein phosphatase 2B, PP2B), in vasopressin escape was studied since aldosterone activates calcineurin in rat cortical collecting ducts. Tacrolimus, a calcineurin inhibitor, blunted vasopressin escape in rats compared with the control rats, increased UT-A1, AQP2, and pS256-AQP2, and decreased pS261-AQP2 protein abundances. Our results indicate that aldosterone regulates vasopressin escape through calcineurin-mediated protein changes in UT-A1 and AQP2.

Combined Angio-CT Systems: A Roadmap Tool for Precision Therapy in Interventional Oncology.

Combined angiography-CT (angio-CT) systems, which combine traditional angiographic imaging with cross-sectional imaging, are a valuable tool for interventional radiology. Although cone-beam CT (CBCT) technology from flat-panel angiography systems has been established as an adjunct cross-sectional imaging tool during interventional procedures, the intrinsic advantages of angio-CT systems concerning superior soft-tissue imaging and contrast resolution, along with operational ease, have sparked renewed interest in their use in interventional oncology procedures. Owing to increases in affordability and usability due to an improved workflow, angio-CT systems have become a viable alternative to stand-alone flat-panel angiographic systems equipped with CBCT. This review aims to provide a comprehensive technical and clinical guide for the use of angio-CT systems in interventional oncology. The basic concepts related to the use of angio-CT systems, including concepts related to workflow setup, imaging characteristics, and acquisition parameters, will be discussed. Additionally, an overview on the clinical applications and the benefits of angio-CT systems in routine therapeutic and palliative interventional oncology procedures will be reviewed. Keywords: Ablation Techniques, CT-Angiography, Interventional-Body, Interventional-MSK, Chemoembolization, Embolization, Radiation Therapy/Oncology, Abdomen/GI, Skeletal-Axial Supplemental material is available for this article. © RSNA, 2021.

The Cumulative Perioperative Model: Predicting 30-Day Mortality in Abdominal Surgery Cancer Patients.

OBJECTIVES: 1) To develop a cumulative perioperative model (CPM) using the hospital clinical course of abdominal surgery cancer patients that predicts 30 and 90-day mortality risk; 2) To compare the predictive ability of this model to ten existing other models. MATERIALS AND METHODS: We constructed a multivariate logistic regression model of 30 (90)-day mortality, which occurred in 106 (290) of the cases, using 13,877 major abdominal surgical cases performed at the University of Texas MD Anderson Cancer Center from January 2007 to March 2014. The model includes race, starting location (home, inpatient ward, intensive care unit or emergency center), Charlson Comorbidity Index, emergency status, ASA-PS classification, procedure, surgical Apgar score, destination after surgery (hospital ward location) and delayed intensive care unit admit within six days. We computed and compared the model mortality prediction ability (C-statistic) as we accumulated features over time. RESULTS: We were able to predict 30 (90)-day mortality with C-statistics from 0.70 (0.71) initially to 0.87 (0.84) within six days postoperatively. CONCLUSION: We achieved a high level of model discrimination. The CPM enables a continuous cumulative assessment of the patient's mortality risk, which could then be used as a decision support aid regarding patient care and treatment, potentially resulting in improved outcomes, decreased costs and more informed decisions.

Role of PKC and AMPK in hypertonicity-stimulated water reabsorption in rat inner medullary collecting ducts.

Hypertonicity increases water permeability, independently of vasopressin, in the inner medullary collecting duct (IMCD) by increasing aquaporin-2 (AQP2) membrane accumulation. We investigated whether protein kinase C (PKC) and adenosine monophosphate kinase (AMPK) are involved in hypertonicity-regulated water permeability. Increasing perfusate osmolality from 150 to 290 mosmol/kgH2O and bath osmolality from 290 to 430 mosmol/kgH2O significantly stimulated osmotic water permeability. The PKC inhibitors chelerythrine (10 µM) and rottlerin (50 µM) significantly reversed the increase in osmotic water permeability stimulated by hypertonicity in perfused rat terminal IMCDs. Chelerythrine significantly increased phosphorylation of AQP2 at S261 but not at S256. Previous studies show that AMPK is stimulated by osmotic stress. We tested AMPK phosphorylation under hypertonic conditions. Hypertonicity significantly increased AMPK phosphorylation in inner medullary tissues. Blockade of AMPK with Compound C decreased hypertonicity-stimulated water permeability but did not alter phosphorylation of AQP2 at S256 and S261. AICAR, an AMPK stimulator, caused a transient increase in osmotic water permeability and increased phosphorylation of AQP2 at S256. When inner medullary tissue was treated with the PKC activator phorbol dibutyrate (PDBu), the AMPK activator metformin, or both, AQP2 phosphorylation at S261 was decreased with PDBu or metformin alone, but there was no additive effect on phosphorylation with PDBu and metformin together. In conclusion, hypertonicity regulates water reabsorption by activating PKC. Hypertonicity-stimulated water reabsorption by PKC may be related to the decrease in endocytosis of AQP2. AMPK activation promotes water reabsorption, but the mechanism remains to be determined. PKC and AMPK do not appear to act synergistically to regulate water reabsorption.

Does deep sedation with propofol affect adenoma detection rates in average risk screening colonoscopy exams?

AIM: To determine the effect of sedation with propofol on adenoma detection rate (ADR) and cecal intubation rates (CIR) in average risk screening colonoscopies compared to moderate sedation. METHODS: We conducted a retrospective chart review of 2604 first-time average risk screening colonoscopies performed at MD Anderson Cancer Center from 2010-2013. ADR and CIR were calculated in each sedation group. Multivariable regression analysis was performed to adjust for potential confounders of age and body mass index (BMI). RESULTS: One-third of the exams were done with propofol (n = 874). Overall ADR in the propofol group was significantly higher than moderate sedation (46.3% vs 41.2%, P = 0.01). After adjustment for age and BMI differences, ADR was similar between the groups. CIR was 99% for all exams. The mean cecal insertion time was shorter among propofol patients (6.9 min vs 8.2 min; P < 0.0001). CONCLUSION: Deep sedation with propofol for screening colonoscopy did not significantly improve ADR or CIR in our population of average risk patients. While propofol may allow for safer sedation in certain patients (e.g., with sleep apnea), the overall effect on colonoscopy quality metrics is not significant. Given its increased cost, propofol should be used judiciously and without the implicit expectation of a higher quality screening exam.

Beat to Beat: A Measured Look at the History of Pulse Oximetry.

It can be argued that pulse oximetry is the most important technological advancement ever made in monitoring the well-being and safety of patients undergoing anesthesia. Before its development, the physical appearance of the patient and blood gas analysis were the only methods of assessing hypoxemia in patients. The disadvantages of blood gas analysis are that it is not without pain, complications, and most importantly does not provide continuous, real-time data. Although it has become de rigueur to use pulse oximetry for every anesthetic, the road leading to pulse oximetry began long ago.

Effect of adjunctive dexmedetomidine on postoperative intravenous opioid administration in patients undergoing thyroidectomy in an ambulatory setting.

STUDY OBJECTIVE: Two of the most feared complications for patients undergoing thyroid surgery are pain and postoperative nausea and vomiting. Thyroidectomy is considered high risk for postoperative nausea and vomiting, and recent studies have looked at adjuncts to treat pain, limit narcotic use, "fast-track" the surgical process, and enhance recovery without compromising the patient's safety. One such perioperative medication of interest is dexmedetomidine (Dex), a centrally acting α-2 agonist that has been associated with reducing pain and postoperative opioid consumption. Our aim was to examine the effectiveness of Dex as an adjunctive intraoperative medication to reduce postoperative narcotic requirements in patients undergoing outpatient thyroid surgery. DESIGN, SETTING, PATIENTS AND INTERVENTION: After obtaining approval from the Institutional Review Board at The University of Texas MD Anderson Cancer Center, we searched the electronic medical record for the period October 2013 to March 2015 to identify patients who had undergone thyroid surgery in the ambulatory setting under general anesthesia. MEASUREMENTS AND MAIN RESULTS: A total of 71 patients underwent thyroidectomy or thyroid lobectomy in the outpatient setting. Of the patients receiving adjunctive Dex, a lower proportion (50%, n=9) received postoperative intravenous opioids when compared with control patients (79%, n=42) (P=.017). One patient (5%) in the Dex group required rescue postoperative antiemetics as compared to 11 (21%) patients in the control group (P=.273). CONCLUSIONS: Our data suggest that intraoperative use of Dex reduced narcotic administration in the postoperative period among study population patients undergoing thyroidectomy.

Phosphatase inhibition increases AQP2 accumulation in the rat IMCD apical plasma membrane.

Vasopressin triggers the phosphorylation and apical plasma membrane accumulation of aquaporin 2 (AQP2), and it plays an essential role in urine concentration. Vasopressin, acting through protein kinase A, phosphorylates AQP2. However, the phosphorylation state of AQP2 could also be affected by the action of protein phosphatases (PPs). Rat inner medullas (IM) were incubated with calyculin (PP1 and PP2A inhibitor, 50 nM) or tacrolimus (PP2B inhibitor, 100 nM). Calyculin did not affect total AQP2 protein abundance (by Western blot) but did significantly increase the abundances of pS256-AQP2 and pS264-AQP2. It did not change pS261-AQP2 or pS269-AQP2. Calyculin significantly enhanced the membrane accumulation (by biotinylation) of total AQP2, pS256-AQP2, and pS264-AQP2. Likewise, immunohistochemistry showed an increase in the apical plasma membrane association of pS256-AQP2 and pS264-AQP2 in calyculin-treated rat IM. Tacrolimus also did not change total AQP2 abundance but significantly increased the abundances of pS261-AQP2 and pS264-AQP2. In contrast to calyculin, tacrolimus did not change the amount of total AQP2 in the plasma membrane (by biotinylation and immunohistochemistry). Tacrolimus did increase the expression of pS264-AQP2 in the apical plasma membrane (by immunohistochemistry). In conclusion, PP1/PP2A regulates the phosphorylation and apical plasma membrane accumulation of AQP2 differently than PP2B. Serine-264 of AQP2 is a phosphorylation site that is regulated by both PP1/PP2A and PP2B. This dual regulatory pathway may suggest a previously unappreciated role for multiple phosphatases in the regulation of urine concentration.

Metformin, an AMPK activator, stimulates the phosphorylation of aquaporin 2 and urea transporter A1 in inner medullary collecting ducts.

Nephrogenic diabetes insipidus (NDI) is characterized by production of very large quantities of dilute urine due to an inability of the kidney to respond to vasopressin. Congenital NDI results from mutations in the type 2 vasopressin receptor (V2R) in ∼90% of families. These patients do not have mutations in aquaporin-2 (AQP2) or urea transporter UT-A1 (UT-A1). We tested adenosine monophosphate kinase (AMPK) since it is known to phosphorylate another vasopressin-sensitive transporter, NKCC2 (Na-K-2Cl cotransporter). We found AMPK expressed in rat inner medulla (IM). AMPK directly phosphorylated AQP2 and UT-A1 in vitro. Metformin, an AMPK activator, increased phosphorylation of both AQP2 and UT-A1 in rat inner medullary collecting ducts (IMCDs). Metformin increased the apical plasma membrane accumulation of AQP2, but not UT-A1, in rat IM. Metformin increased both osmotic water permeability and urea permeability in perfused rat terminal IMCDs. These findings suggest that metformin increases osmotic water permeability by increasing AQP2 accumulation in the apical plasma membrane but increases urea permeability by activating UT-A1 already present in the membrane. Lastly, metformin increased urine osmolality in mice lacking a V2R, a mouse model of congenital NDI. We conclude that AMPK activation by metformin mimics many of the mechanisms by which vasopressin increases urine-concentrating ability. These findings suggest that metformin may be a novel therapeutic option for congenital NDI due to V2R mutations.

Phenothiazine vs 5HT3 antagonist prophylactic regimens to prevent Post-Anesthesia Care Unit rescue antiemetic: an observational study.

PURPOSE: Our practitioners are asked to consider a patient's postoperative nausea and vomiting (PONV) risk profile when developing their prophylactic antiemetic strategy. There is wide variation in employed strategies, and we have yet to determine the most effective PONV prophylactic regimen. The objective of this study is to compare prophylactic antiemetic regimens containing: phenothiazines to 5HT3 antagonists for effectiveness at reducing the incidence of Post-Anesthesia Care Unit (PACU) rescue antiemetic administration. METHODS: This is an observational study of 4,392 nonsmoking women who underwent general anesthesia for breast surgery from 1/1/2009 through 6/30/2012. Previous history of PONV or motion sickness (HxPONV/MS) and the use of PACU opioids were recorded. Prophylactic antiemetic therapy was left to the discretion of the anesthesia care team. We compared phenothiazines and 5HT3 antagonists alone and with a glucocorticoid to determine the most effective treatment regimen in our practice for the prevention of the administration of PACU rescue antiemetics. RESULTS: Patients who received a phenothiazine regimen compared to a 5HT3 antagonist regimen were less likely to have an antiemetic administered in the PACU (p=0.0100) and this significant difference in rates holds in a logistic regression model adjusted for HxPONV/MS and PACU Opioid use (p=0.0103). CONCLUSIONS: Based on our findings our clinicians are encouraged to administer a combination of a phenothiazine and a glucocorticoid in female, nonsmoking surgical breast patients for the prevention of PACU rescue antiemetic administration.

Evaluation of OPEN zinc finger nucleases for direct gene targeting of the ROSA26 locus in mouse embryos.

Zinc finger nucleases (ZFNs) enable precise genome modification in a variety of organisms and cell types. Commercial ZFNs were reported to enhance gene targeting directly in mouse zygotes, whereas similar approaches using publicly available resources have not yet been described. Here we report precise targeted mutagenesis of the mouse genome using Oligomerized Pool Engineering (OPEN) ZFNs. OPEN ZFN can be constructed using publicly available resources and therefore provide an attractive alternative for academic researchers. Two ZFN pairs specific to the mouse genomic locus gt(ROSA26)Sor were generated by OPEN selections and used for gene disruption and homology-mediated gene replacement in single cell mouse embryos. One specific ZFN pair facilitated non-homologous end joining (NHEJ)-mediated gene disruption when expressed in mouse zygotes. We also observed a single homologous recombination (HR)-driven gene replacement event when this ZFN pair was co-injected with a targeting vector. Our experiments demonstrate the feasibility of achieving both gene ablation through NHEJ and gene replacement by HR by using the OPEN ZFN technology directly in mouse zygotes.

Who is at risk for postdischarge nausea and vomiting after ambulatory surgery?

BACKGROUND: About one in four patients suffers from postoperative nausea and vomiting. Fortunately, risk scores have been developed to better manage this outcome in hospitalized patients, but there is currently no risk score for postdischarge nausea and vomiting (PDNV) in ambulatory surgical patients. METHODS: We conducted a prospective multicenter study of 2,170 adults undergoing general anesthesia at ambulatory surgery centers in the United States from 2007 to 2008. PDNV was assessed from discharge until the end of the second postoperative day. Logistic regression analysis was applied to a development dataset and the area under the receiver operating characteristic curve was calculated in a validation dataset. RESULTS: The overall incidence of PDNV was 37%. Logistic regression analysis of the development dataset (n=1,913) identified five independent predictors (odds ratio; 95% CI): female gender (1.54; 1.22 to 1.94), age less than 50 yr (2.17; 1.75 to 2.69), history of nausea and/or vomiting after previous anesthesia (1.50; 1.19 to 1.88), opioid administration in the postanesthesia care unit (1.93; 1.53 to 2.43), and nausea in the postanesthesia care unit (3.14; 2.44-4.04). In the validation dataset (n=257), zero, one, two, three, four, and five of these factors were associated with a PDNV incidence of 7%, 20%, 28%, 53%, 60%, and 89%, respectively, and an area under the receiver operating characteristic curve of 0.72 (0.69 to 0.73). CONCLUSIONS: PDNV affects a substantial number of patients after ambulatory surgery. We developed and validated a simplified risk score to identify patients who would benefit from long-acting prophylactic antiemetics at discharge from the ambulatory care center.

Generation of adipose stromal cell-derived hepatic cells.

The demand for primary human hepatocytes to test the toxicity of new drug candidates and to develop cell therapies for liver disease far exceed the number of hepatocytes that can be isolated from donated tissues. Less than 700 whole livers per year are available for research applications. The ability to utilize nonhepatic progenitor cells, such as adipose stromal cells (ASCs), to generate derivatives that mimic primary human hepatocytes would enable the scale-up production of cell products for bioartifical liver-assist devices, cell therapy, and drug discovery applications. ASC hepatogenesis is a rapidly evolving field with improved protocols continually being reported in the literature. In this chapter, current and effective protocols for the expansion, hepatic differentiation, and functional characterization of ASC-derived hepatic cells are outlined. Two major features distinguish optimized methodologies: (a) cytokine-mediated "reprogramming" of mesenchymal ASCs to enable transdifferentiation into endodermal cell lineages, and (b) treatment with sequential media formulations containing factors/extracellular matrices that mimic the temporal expression profiles seen during fetal liver development. Criteria for success are acquisition of hepatic functional activities, such as albumin/urea production and p450 CYP activities, at levels that approach those observed in primary human hepatocyte controls.

Ongoing provision of individual clinician performance data improves practice behavior.

BACKGROUND: Clinical practice guidelines summarize evidence from science and attempt to translate those findings into clinical practice. Pervasive and consistent adoption of these guidelines into daily provider practice has proven slow. METHODS: Using postoperative nausea and vomiting (PONV) prophylaxis guideline compliance as our metric, we compared the effects of continuing medical education (CME) alone (I), CME with a single snapshot of provider compliance (II), and ongoing reporting of provider compliance data without further CME (III). We retrospectively analyzed guideline compliance of 23,279 anesthetics at the University of Texas M.D. Anderson Cancer Center. Compliance was defined as a patient with 1 risk factor for PONV receiving at least 1 antiemetic, 2 risk factors receiving at least 2 antiemetics, and 3 risk factors receiving at least 3 antiemetics. Drugs of the same class were counted as single antiemetic administration. Propofol-based anesthetic techniques were counted as receiving 1 antiemetic. Patients with 0 risk factors for PONV were not included. We estimated the compliance rates for each of the 4 time periods of the study adjusting for multiple observations on the same clinician. Individual performance feedback was given once at 6 months after intervention I coincident with a refresher presentation on PONV (start of intervention II) and on an ongoing quarterly basis during intervention III. RESULTS: Compliance rates were not significantly influenced with CME (intervention I) compared with baseline behavior (54.5% vs 54.4%, P = 0.9140). Significant improvement occurred during the time period when CME was paired with performance data (intervention II) compared with intervention I (59.2% vs 54.4%, P = 0.0002). Further significant improvement occurred when data alone were presented (intervention III) compared with intervention II (65.1% vs 59.2%, P < 0.0001). For patients with 3 risk factors, we saw significant improvement in compliance rates during intervention III (P = 0.0002). In post hoc analysis of overtreatment, the percentage differences between the baseline and time period III decreased as the number of risk factors increased. CONCLUSIONS: We observed the greatest improvement in guideline compliance with ongoing personal performance feedback. Provider feedback can be an effective tool to modify clinical practice but can have unanticipated consequences.