Effectiveness of Implementing Evidence‐based Interventions to Reduce C‐spine Image Ordering in the Emergency Department: A Systematic Review

Objectives

Appropriate use of imaging for adult patients with cervical spine (C‐spine) injuries in the emergency department (ED) is a longstanding issue. Guidance for C‐spine ordering exists; however, the effectiveness of the decision support implementation in the ED is not well studied. This systematic review examines the implementation and effectiveness of evidence‐based interventions aimed at reducing C‐spine imaging in adults presenting to the ED with neck trauma.

Methods

Six electronic databases and the gray literature were searched. Comparative intervention studies were eligible for inclusion. Two independent reviewers screened for study eligibility, study quality, and extracted data. The change in imaging was reported using individual odds ratios (ORs) with 95% confidence intervals (CIs) using random effects.

Results

A total of 990 unique citations were screened for relevance of which six before–after studies and one randomized controlled trial were included. None of the studies were assessed as high quality. Interventions consisted primarily of locally developed guidelines or established clinical decision rules such as the NEXUS or the Canadian C‐spine rule. Overall, implementation of interventions aimed at reducing C‐spine image ordering resulted in a statistically significant reduction in imaging (OR = 0.69, 95% CI = 0.51–0.93); however, heterogeneity was high (I² = 82%). Subgroup analysis revealed no differences between studies that specified enrolling alert and stable patients compared to unspecified trauma (p = 0.81) or between studies employing multifaceted versus nonmultifaceted interventions (p = 0.66). While studies generally provided details on implementation strategies (e.g., teaching sessions, pocket cards, posters, computerized decision support) the effectiveness of these implementation strategies were frequently not reported.

Conclusion

There is moderate evidence regarding the effectiveness of interventions to reduce C‐spine image ordering in adult patients seen in the ED with neck trauma. Given the national and international focus on improving appropriateness and reducing unnecessary C‐spine imaging through campaigns such as Choosing Wisely, additional interventional research in this field is warranted.

     

Experimental Referred Pain Extends Toward Previously Injured Location: An Explorative Study

Facilitated pain mechanisms have been demonstrated in musculoskeletal pain, but it is unclear whether a recent painful injury leaves the pain system sensitized. Pain characteristics were assessed in individuals who recently recovered from ankle pain (recovered pain group; n?=?25) and sex-matched control subjects (n?=?25) in response to tonic pressure pain and saline-induced pain applied at the shin muscle. Pain intensity and pain referral patterns were recorded bilaterally after the painful muscle stimulus. Pressure pain thresholds were measured at the lower legs and shoulder. Cuff pressure algometry on the lower leg was used to assess pain detection threshold, pressure evoking 6-cm pain score on a 10-cm visual analog scale, pain tolerance, temporal summation of pain, and conditioned pain modulation. Compared with in control subjects, saline-induced and pressure-induced pain in the shin muscle were more frequently felt as referred pain in the previously painful ankle (P < .05), and the pain area within the previously affected ankle was larger after saline-induced pain (P < .05). In the recovered pain group, conditioned pain modulation responses and the cuff pressure needed to reach a 6-cm pain score on a 10-cm visual analog scale was higher in the previously painful leg compared with in the contralateral leg (P < .05). No group differences were found in pressure pain threshold, pain detection threshold, pain tolerance, and temporal summation of pain.

Initial treatment with fixed-dose combination rosiglitazone/glimepiride in patients with previously untreated type 2 diabetes

Aim: This study assessed the efficacy and safety of two different dosing regimens of fixed‐dose combination (FDC) rosiglitazone (RSG) plus glimepiride (GLIM) compared with RSG or GLIM monotherapy in drug‐naive subjects with type 2 diabetes mellitus (T2DM). Methods: Drug‐naive subjects (n = 901) were enrolled into this 28‐week, double‐blind, parallel‐group study if their glycosylated haemoglobin A_1c (HbA_1c) was >7.5% but ≤12%. Subjects were randomized to receive either GLIM [4 mg once daily (OD) maximal], RSG (8 mg OD maximal) or RSG/GLIM FDC regimen A (4 mg/4 mg OD maximal) or RSG/GLIM FDC regimen B (8 mg/4 mg OD maximal). Patients were assessed for efficacy and safety every 4 weeks for the first 12 weeks of the study, and at weeks 20 and 28. The primary efficacy endpoint was change in HbA_1c from baseline. Key secondary endpoints included the proportion of patients achieving recommended HbA_1c and fasting plasma glucose (FPG) targets; change from baseline in FPG, insulin, C‐reactive protein (CRP), adiponectin, free fatty acids and lipids; and percentage change in homeostasis model assessment‐estimated insulin sensitivity and β‐cell function. Safety evaluations included adverse‐event (AE) monitoring and clinical laboratory evaluations. Results: At week 28, both RSG/GLIM FDC regimens significantly reduced HbA_1c (mean ± s.d.: ?2.4 ± 1.4% FDC regimen A; ?2.5 ± 1.4% FDC regimen B) to a greater extent than RSG (?1.8 ± 1.5%) or GLIM (?1.7 ± 1.4%) monotherapy (model‐adjusted mean treatment difference, p < 0.0001 vs. both RSG and GLIM). Significantly more subjects achieved HbA_1c target levels of ≤6.5 and <7% with either RSG/GLIM FDC regimen compared with RSG or GLIM alone (model‐adjusted odds ratio, p < 0.0001 for both comparisons). Similarly, a significantly greater reduction in FPG levels was observed in subjects treated with the RSG/GLIM FDC [mean ± s.d. (mg/dl): ?69.5 ± 57.5 FDC regimen A; ?79.9 ± 56.8 FDC regimen B) compared with RSG (?56.6 ± 58.1) or GLIM (?42.2 ± 66.1) monotherapy (model‐adjusted mean treatment difference, p < 0.0001 for both comparisons). Improvement in CRP was also observed in subjects who were treated with a RSG/GLIM FDC or RSG monotherapy compared with GLIM monotherapy. RSG/GLIM FDC was generally well tolerated, with no new safety or tolerability issues identified from its monotherapy components, and a similar AE profile was observed across FDC regimens. The most commonly reported AE was hypoglycaemia, and the incidence of confirmed symptomatic hypoglycaemia (3.6–5.5%) was comparable among subjects treated with an RSG/GLIM FDC and GLIM monotherapy. Conclusions: Compared with RSG or GLIM monotherapy, the RSG/GLIM FDC improved glycaemic control with no significant increased risk of hypoglycaemia. RSG/GLIM FDC provides an effective and well‐tolerated treatment option for drug‐naive individuals with T2DM.     

Phorbol ester activation of the protein kinase C pathway inhibits gonadotropin-releasing hormone gene expression.

The effects of the phorbol ester 12-O-tetradecanoyl phorbol 13-acetate (TPA), an activator of protein kinase C (PKC), and the PKC inhibitor staurosporine on GnRH secretion and mRNA levels were studied in GT1-7 hypothalamic neuronal cells. Dose-response and time-course studies revealed that TPA (10(-8) M) acutely increased GnRH secretion 3-fold at 3-6 h, which then declined to baseline at 24 h, while it progressively decreased GnRH mRNA levels by 50% and 70% at 6 and 24 h, respectively. To ensure that these effects were due to activation and not down-regulation of PKC, cells were treated for 30 min with TPA (10(-8) M). This brief exposure to TPA also resulted in a decrease (60%) in GnRH mRNA levels at 6 h, with a 1.5- to 2-fold increase in GnRH secretion compared to control values, suggesting that activation of PKC decreases the pretranslational expression of GnRH while increasing GnRH secretion. Additional studies measured PKC activity and documented a shift from a cytosolic to a membrane fraction after incubation with TPA, again supporting PKC activation. Exposure of GT1-7 cells to staurosporine (10(-8) M), a PKC inhibitor, resulted in no change in the level of GnRH mRNA or secretion at 6 h. However, incubation with both TPA and staurosporine prevented the decrease in GnRH mRNA levels and partially blocked the increase in GnRH secretion induced by TPA. We conclude that TPA, by activating the PKC pathway, acutely increases GnRH secretion, but dramatically decreases GnRH gene expression. The exact mechanism of these divergent effects on the synthesis and secretion of GnRH remain to be elucidated.     

Compensatory gait mechanics in patients with unilateral knee arthritis

OBJECTIVE: Few studies exist on gait adaptation caused by knee osteoarthritis (OA), and those have only explored adaptations of the kinematics and kinetics of the knee joint itself. We characterize ankle, knee, hip, and low back mechanical energy expenditures (MEE) and compensations (MEC) during gait in patients with knee OA. METHODS: Thirteen elderly patients with unilateral knee OA and 10 matched healthy elderly controls were studied during preferred and paced speed gait. Gait speed, step length, and lower extremity and low back joint MEE and MEC were compared between groups. RESULTS: Patients with knee OA had lower, but not significantly different, walking speed and step length compared to the controls, and had significantly different joint kinetic profiles. Patients had reduced ankle power at terminal stance, lacked a second positive peak in knee power, and had increased power absorption at the hip. Abnormal knee kinematics were exaggerated when walking at a paced speed, but hip kinetics normalized among patients with OA. CONCLUSION: Reduced ankle plantar-flexion power in patients with knee OA was probably due to disrupted transfer of energy through the knee. Lack of concentric knee power supports prior studies' conclusions that patients with knee OA avoid using their quadriceps to stabilize the knee, probably to reduce articular loads. Patients with knee OA increase eccentric hip power due to increased hip extension caused by abnormal knee kinematics, potentially increasing hip articular forces. This passive mechanism, however, may assist in the advancement of the leg into swing phase.     

A synthetic peptide substrate specific for casein kinase II.

A synthetic peptide having the sequence Arg-Arg-Arg-Glu-Glu-Thr-Glu-Glu-Glu was found to serve as a convenient substrate for the protein kinase generally referred to as casein kinase II. The enzyme exhibited an apparent Km of 500 microM for the peptide, as compared to an apparent Km of 50 microM for casein. The maximum velocities for phosphorylation of the peptide and of casein were similar. The peptide was not phosphorylated by any of eight other protein kinases, all of which were shown to be active toward their known substrates. The peptide was used to monitor activity during steps in the purification of casein kinase II from bovine liver. These experiments demonstrated that with this peptide it is now possible to obtain specific measurements of casein kinase II activity in crude enzyme preparations.     

Local injection of stem cell factor (SCF) improves myocardial homing of systemically delivered c-kit + bone marrow-derived stem cells

AIMS: Recent studies have shown that stem cell therapy may alleviate the detrimental effects of myocardial infarction. Yet, most of these reports observed only modest effects on cardiac function, suggesting that there still is need for improvement before widespread clinical use. One potential approach would be to increase migration of stem cells to the heart. We therefore tested whether local administration of stem cell factor (SCF) improves myocardial homing of intravenously infused lin-/c-kit+ stem cells after myocardial infarction. METHODS AND RESULTS: Myocardial infarction was induced in mice via ligation of the left anterior descending artery and 2.5 microg of SCF were injected into the peri-infarct zone. Sham-operated mice and animals with intramyocardial injection of phosphate-buffered saline (PBS) served as controls. Twenty-four hours after myocardial infarction, lin-/c-kit+ stem cells were separated from murine bone marrow by magnetic cell sorting, labelled with the green fluorescent cell tracker CFDA or 111 Indium, and subsequently 750 000 labelled cells were systemically infused via the tail vein. Another 24 or 72 h later, respectively (i.e. 48 and 96 h after myocardial infarction), hearts were removed and analysed for myocardial homing of stem cells. Green fluorescent stem cells were exclusively detected in the peri-infarct zone of animals having prior SCF treatment. Radioactive measurements revealed that an intramyocardial SCF injection significantly amplified myocardial homing of lin-/c-kit+ stem cells compared to animals with PBS injections (3.58 +/- 0.53 vs. 2.28 +/- 0.23 cpm/mg/10(6)cpm, +60%, P < 0.05) and sham-operated mice without myocardial infarction (3.58 +/- 0.53 vs. 1.95 +/- 0.22 cpm/mg/10(6)cpm, +85%, P < 0.01). Similar results were obtained 72 h after stem cell injection. CONCLUSION: We demonstrate that intramyocardial administration of SCF sustainably directs more lin-/c-kit+ stem cells to the heart. Future studies will have to show whether higher levels of myocardial SCF (i.e. by virus-mediated gene transfer) can further improve homing of systemically delivered c-kit+ stem cells and thus favourably influence cardiac remodelling following myocardial infarction.     

Advanced Functional Polymers for Increasing the Stability of Organic Photovoltaics

The development of new advanced polymers for improving the stability of OPV is reviewed. Two main degradation pathways for the OPV active layer are identified: photochemically initiated reactions primarily starting in the side chains and morphological changes that degrade the important nanostructure. Chemical units can be introduced that impart an increased stability. Similarly, the morphological degradation of the optimal nanostructure can be reduced. Active polymers and blends with acceptor material are used to create nanoparticle links with controlled size. Most of these advanced polymers and processing methods have only been utilized in small‐scale devices prepared by standard techniques such as spin coating, but a few cases of roll‐to‐roll processed solar cells with heat‐cleaved side chains are discussed.