A Placebo-controlled Study of PF-06473871 (Anti-Connective Tissue Growth Factor Antisense Oligonucleotide) in Reducing Hypertrophic Skin Scarring.

BACKGROUND: Connective tissue growth factor (CTGF) is a matricellular protein that plays a key role in wound healing and scar formation. Inhibition of CTGF by a specific antisense oligonucleotide significantly reduced scarring and fibrosis in animal models. This study examined whether an antisense oligonucleotide that inhibits human CTGF expression could reduce the severity of hypertrophic scar formation in patients following surgical revision of preexisting breast scars. METHODS: This study was a 24-week multicenter, randomized, double-blind, within-subject, placebo-controlled phase 2b study evaluating the efficacy and safety of PF-06473871 in 2 regimens of either 3 or 4 intradermal injections (postsurgery weeks 2, 5, 8, and 11) of 5 mg/cm adjacent to the new surgical incision. One hundred subjects with bilateral hypertrophic scars resulting from prior breast surgery were randomized. Efficacy was determined by the Patient and Observer Scar Assessment Scale (POSAS). RESULTS: The Physician/Observer POSAS overall opinion score at (week 24) for the 4-injection regimen demonstrated a statistically significant (P = 0.022) treatment difference from placebo of 0.68, and the treatment difference for the 3-injection regimen was nonsignificant (P = 0.4). Physician evaluation of scar severity at (week 24) with the photo-guide in the 4-injection regimen had a significant reduction (point estimate of treatment difference of 0.43 favoring PF-06473871). The surgical effect was approximately 2.0 at week 24 and was nearly 3 times greater than the treatment effect. Patient evaluations using the POSAS and photo-guide were not significantly improved with either dose regimen. PF-06473871 was generally well tolerated systemically and locally. CONCLUSION: The 4-dose regimen of PF-06473871 provided statistically significant improvement, inhibiting severity of hypertrophic scar formation based on physician assessment. However, the effect of revision surgery alone is significant and may dominate the treatment effect of PF-06473871.

Anti-CTGF Oligonucleotide Reduces Severity of Postsurgical Hypertrophic Scars in a Randomized, Double-Blind, Within-Subject, Placebo-Controlled Study.

BACKGROUND: Connective tissue growth factor (CTGF) levels are up-regulated in wounded skin and are thought to play a major role in scar formation. An antisense oligonucleotide targeting CTGF was evaluated in adult patients undergoing hypertrophic scar revision surgery, to determine effects on reducing the severity of subsequent scars. METHODS: In a randomized, double-blind, within-subject, placebo-controlled study, 23 female subjects (aged 28 to 55 years) with bilateral, symmetric, hypertrophic surgical scars of the breast underwent scar revision surgery. The resulting breast incisions were randomized to receive EXC 001 (5 mg/cm) or placebo injected intradermally at postsurgery weeks 2, 5, 8, and 11. Scar severity assessments were performed at weeks 12 and 24 by an expert panel using blinded photographs, and by physicians and subjects using a scar scoring scale, the Patient and Observer Scar Assessment Scale. An assumption of the design is that within-subject variance would be small and that whatever within-subject variance there was would be controlled through the randomization process. RESULTS: EXC 001 significantly reduced scar severity at both 12 and 24 weeks after scar revision surgery in all three measures (expert panel and physician Patient and Observer Scar Assessment Scale, p < 0.001; Patient and Observer Scar Assessment Scale, p < 0.003). CONCLUSIONS: This study provided positive preliminary data that intradermal injection of EXC 001 produced a significant reduction in severity of postsurgical skin scars, as measured by physicians, subjects, and an expert panel. This study provided evidence that suppression of CTGF could be a viable strategy for hypertrophic scar reduction therapy and that further study of the antisense oligonucleotide EXC 001 was indicated. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

Outcomes in Patients with Vasodilatory Shock and Renal Replacement Therapy Treated with Intravenous Angiotensin II.

OBJECTIVE: Acute kidney injury requiring renal replacement therapy in severe vasodilatory shock is associated with an unfavorable prognosis. Angiotensin II treatment may help these patients by potentially restoring renal function without decreasing intrarenal oxygenation. We analyzed the impact of angiotensin II on the outcomes of acute kidney injury requiring renal replacement therapy. DESIGN: Post hoc analysis of the Angiotensin II for the Treatment of High-Output Shock 3 trial. SETTING: ICUs. PATIENTS: Patients with acute kidney injury treated with renal replacement therapy at initiation of angiotensin II or placebo (n = 45 and n = 60, respectively). INTERVENTIONS: IV angiotensin II or placebo. MEASUREMENTS AND MAIN RESULTS: Primary end point: survival through day 28; secondary outcomes included renal recovery through day 7 and increase in mean arterial pressure from baseline of ≥ 10 mm Hg or increase to ≥ 75 mm Hg at hour 3. Survival rates through day 28 were 53% (95% CI, 38%-67%) and 30% (95% CI, 19%-41%) in patients treated with angiotensin II and placebo (p = 0.012), respectively. By day 7, 38% (95% CI, 25%-54%) of angiotensin II patients discontinued RRT versus 15% (95% CI, 8%-27%) placebo (p = 0.007). Mean arterial pressure response was achieved in 53% (95% CI, 38%-68%) and 22% (95% CI, 12%-34%) of patients treated with angiotensin II and placebo (p = 0.001), respectively. CONCLUSIONS: In patients with acute kidney injury requiring renal replacement therapy at study drug initiation, 28-day survival and mean arterial pressure response were higher, and rate of renal replacement therapy liberation was greater in the angiotensin II group versus the placebo group. These findings suggest that patients with vasodilatory shock and acute kidney injury requiring renal replacement therapy may preferentially benefit from angiotensin II.

Pulmonary CTA in sickle cell patients: quantitative assessment of enhancement quality.

PURPOSE: The purpose of this study was to validate the observation that pulmonary artery (PA) enhancement is often decreased in sickle cell disease (SCD) patients imaged with MDCT for suspected pulmonary embolism and determine whether contrast infusion parameters are accountable for lower enhancement levels. MATERIALS AND METHODS: Retrospective comparison of 35 adult SCD patients imaged for suspected pulmonary embolism (PE) in our emergency department using 128-slice dual source MDCT scanner to 34 age and weight matched adult controls. Bolus tracking data was recorded, and enhancement levels of the main PA and descending aorta were measured. Electronic records were reviewed for demographics, imaging and lab correlation, and infusion parameters. RESULTS: Age, weight, contrast infusion rate, and contrast volume were similar for both SCD and control patients. SCD patients had significantly lower main PA enhancement (mean 233 HU, range 151-361 HU) than the control subjects (mean 290 HU, range 138-487 HU) (p < 0.001). Most (74%) SCD subjects had PA enhancement that was <250 HU, while most (68%) control patients had PA enhancement ≥250 HU. Change in PA enhancement per second during bolus tracking was lower in SCD patients (12 HU/s, range -24 to 91 HU/s) than control patients (mean 30 HU/s, range -37 to 138 HU/s), although the difference was not statistically significant (p = 0.08). Hemoglobin levels were significantly lower in the SCD cohort (p < 0.001). CONCLUSION: In this series of adult SCD patients with suspected PE imaged with MDCT, main PA enhancement level was lower than controls. Quality improvement investigations should focus on protocol optimization to improve enhancement quality and likelihood of a definitive diagnosis.

Partnering With Your Health System to Select and Implement Clinical Decision Support for Imaging.

Recent legislation mandates the documentation of appropriateness criteria consultation when ordering advanced imaging for Medicare patients to remain eligible for reimbursement. Implementation of imaging clinical decision support (CDS) is a solution adopted by many systems to automate compliance with the new requirements. This article is intended to help radiologists who are employed by, contracted with, or otherwise affiliated with systems planning to implement CDS in the near future and ensure that they are able to understand and contribute to the process wherever possible. It includes an in-depth discussion of the legislation, evidence for and against the efficacy of imaging CDS, considerations for selecting a CDS vendor, tips for configuring CDS in a fashion consistent with departmental goals, and pointers for implementation and change management.

Using Quality Improvement Methods to Improve Patient Experience.

Patient experience is an important component of the overall medical encounter. This paper explores how patient experience is measured and its role in radiology, including its impact on clinical outcomes and reimbursement. Although typically applied to safety and clinical outcomes, quality improvement methodology can also be used to drive improvement efforts centered on patient experience. Applying an established framework for patient-centered care to radiology, this paper provides a number of examples of projects that are likely to yield significant improvement in patient satisfaction measures.

Sonographic findings of typical and atypical scrotal trauma.

This review article illustrates sonographic findings in the setting of accidental and nonaccidental scrotal trauma. Although sonographic findings may be irrespective of the type of trauma, the goals of sonographic evaluation are similar in both atypical and typical mechanisms of scrotal injury. Familiarity with findings such as disruption of testicular integrity or vascularity facilitates prompt diagnosis and plays a critical role in clinical management.

Linking maternal platelet counts with neonatal platelet counts and outcomes using the data repositories of a multihospital health care system.

It is unclear whether neonates born to women with thrombocytopenia during pregnancy are themselves at increased risk for thrombocytopenia at birth. In the current retrospective study, platelet count reference ranges were developed for pregnant women according to trimester, and correlations were sought between the platelet counts of mothers at delivery and their neonates. During the study period, 92,518 platelet counts were recorded on 41,887 pregnant women. A progressive shift toward lower platelet counts in a similarly shaped histogram occurred during pregnancy, with the lower reference range (2.5 percentile) for platelets during the third trimester being 113 × 10(9)/L. Among 11,797 maternal-neonatal pairs following delivery, no correlation was observed between maternal and neonatal counts. However, if the mother's lowest count was <50 × 10(9)/L, the relative risk of any degree of thrombocytopenia in their neonate was 4.6 (95% confidence interval [CI], 1.8 to 33.3) and the relative risk of severe neonatal thrombocytopenia was 7.8 (95% CI, 1.8 to 33.3). The results of the current study demonstrate that platelet counts >75 × 10(9)/L in pregnant women were not associated with an increased risk of neonatal thrombocytopenia, and maternal platelet counts of <50 × 10(9)/L were accompanied by an almost fivefold risk increase of neonatal thrombocytopenia.

Advanced life support performance with manual and mechanical chest compressions in a randomized, multicentre manikin study.

AIM OF THE STUDY: Clinical mechanical chest compression studies report diverging outcomes. Confounding effects of variability in hands-off fraction (HOF) and timing of necessary tasks during advanced life support (ALS) may contribute to this divergence. Study site variability in these factors coupled to randomization of cardiopulmonary resuscitation (CPR) method was studied during simulated cardiac arrest prior to a multicentre clinical trial. METHOD: Ambulance personnel from four sites were tested in randomized, simulated cardiac arrest scenarios with manual CPR or load-distributing band CPR (LDB-CPR) on manikins. Primary emphasis was on HOF and time spent before necessary predefined ALS task (ALS milestones). Results are presented as mean differences (confidence interval). RESULTS: At the site with lowest HOF during manual CPR, HOF deteriorated with LDB-CPR by 0.06 (0.005, 0.118, p=0.04), while it improved at the two sites with highest HOF during manual CPR by 0.07 (0.019, 0.112, p=0.007) and 0.08 (0.004, 0.165, p=0.042). Initial defibrillation was 29 (3, 55, p=0.032)s delayed for LDB-CPR vs. manual CPR. Other ALS milestones trended toward earlier completion with LDB-CPR; only significant for intravenous access, mean difference 70 (24, 115, p=0.003)s. CONCLUSION: In this manikin study, HOF for manual vs. mechanical chest compressions varied between sites. Study protocol implementation should be simulation tested before launching multicentre trials, to optimize performance and improve reliability and scientific interpretation.

Multicenter comparison of the contraceptive ring and patch: a randomized controlled trial.

OBJECTIVE: To understand if the contraceptive ring or patch was more acceptable, as measured primarily by continuation, to women using an oral contraceptive and interested in a nondaily, combined hormonal contraceptive. METHODS: Five hundred women were randomly assigned to use the contraceptive ring (n=249) or contraceptive patch (n=251) for four consecutive menstrual cycles, starting with their next menses. Participants returned for a single follow-up visit during the fourth cycle for an evaluation, which included a questionnaire to assess acceptability and adverse effects. RESULTS: Rates of completion of three cycles were 94.6% (95% confidence interval [CI] 91.0-97.1%) and 88.2% (95% CI 83.4-92.0%) for ring and patch users, respectively (P=.03). Of these women, 71.0% (95% CI 64.8-76.6%) and 26.5% (95% CI 21.0-32.6%), respectively, planned to continue their method after the study (P<.001). Women switching to the patch were significantly more likely than women switching to the ring to experience longer periods (38% compared with 9%), increased dysmenorrhea (29% compared with 16%), frequent nausea (8% compared with 1%), frequent mood swings (14% compared with 8%), and frequent skin rash (12% compared with 2%) and were less likely to experience frequent vaginal discharge (8% compared with 17%). Ring users preferred the ring to the oral contraceptive (P<.001), and patch users preferred the oral contraceptive to the patch (P<.001). Nugent scores increased only in patch users (P=.01), although most of these women were asymptomatic. CONCLUSION: Women satisfied with combined oral contraceptives and interested in a nondaily method are more likely to continue using the contraceptive ring than the contraceptive patch. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00269620. LEVEL OF EVIDENCE: I.

The effects of Computerized Provider Order Entry on medication turn-around time: a time-to-first dose study at the Providence Portland Medical Center.

As the Providence Health System is phasing in its Computerized Provider Order Entry (CPOE) system at the Providence Portland Medical Center, we conducted a study to demonstrate the effects of CPOE on medication turn-around time. Retrospectively, we tracked and compared medication orders that were placed via the existing paper-based system and the CPOE system. The results of this study coincide with, and confirm, previous research that has been performed at large academic medical centers.

Paracervical block and elective abortion: the effect on pain of waiting between injection and procedure.

OBJECTIVE: Our purpose was to assess the effect on pain and patient satisfaction of waiting between paracervical block and dilation during first-trimester abortions. STUDY DESIGN: One hundred ninety-nine women seeking pregnancy termination were randomly assigned to a no-wait group (group 1) and a 3- to 5-minute wait between injection and dilation group (group 2). Subjects rated their pain on a visual analog scale at four times: prior to procedure, with dilation, with aspiration, and 30 to 45 minutes after procedure. RESULTS: No significant differences were observed in pain or satisfaction ratings reported by group 1 (n = 93) and group 2 (n = 101). A significant decrease in pain with dilation (1.21 cm decrease, P =.009) and aspiration (1.15 cm decrease, P =.0015) was observed among patients who received fentanyl. CONCLUSION: Delay between paracervical injection and dilation during first-trimester abortion does not have an impact on patient pain or satisfaction. Fentanyl decreased pain scores by 20% to 25% during the procedure.