There is a tremendous need to enhance nurses' skills so that they achieve competency in EBP in order to ensure the highest quality of care and best population health outcomes. Academic programs should ensure competency in EBP in students by the time of graduation and healthcare systems should set it as an expectation and standard for all clinicians.

Objective: Decades-old, common ICU practices including deep sedation, immobilization, and limited family access are being challenged. We endeavoured to evaluate the relationship between ABCDEF bundle performance and patient-centered outcomes in critical care. Design: Prospective, multicenter, cohort study from a national quality improvement collaborative. Setting: 68 academic, community, and federal ICUs collected data during a 20-month period. Patients: 15,226 adults with at least one ICU day. Interventions: We defined ABCDEF bundle performance (our main exposure) in two ways: 1) complete performance (patient received every eligible bundle element on any given day) and 2) proportional performance (percentage of eligible bundle elements performed on any given day). We explored the association between complete and proportional ABCDEF bundle performance and three sets of outcomes: patient-related (mortality, ICU hospital discharge), symptom-related (mechanical ventilation, coma, delirium, pain, restraint use), and system-related (ICU readmission, discharge destination). All models were adjusted for a minimum of 18 a priori determined potential confounders. Measurements and Results: Complete ABCDEF bundle performance was associated with lower likelihood of seven outcomes: hospital death within 7 days (adjusted hazard ratio, 0.32; CI, 0.17–0.62), next-day mechanical ventilation (adjusted odds ratio [AOR], 0.28; CI, 0.22–0.36), coma (AOR, 0.35; CI, 0.22–0.56), delirium (AOR, 0.60; CI, 0.49–0.72), physical restraint use (AOR, 0.37; CI, 0.30–0.46), ICU readmission (AOR, 0.54; CI, 0.37–0.79), and discharge to a facility other than home (AOR, 0.64; CI, 0.51–0.80). There was a consistent dose-response relationship between higher proportional bundle performance and improvements in each of the above-mentioned clinical outcomes (all p < 0.002). Significant pain was more frequently reported as bundle performance proportionally increased (p = 0.0001). Conclusions: ABCDEF bundle performance showed significant and clinically meaningful improvements in outcomes including survival, mechanical ventilation use, coma and delirium, restraint-free care, ICU readmissions, and post-ICU discharge disposition.

Wellness must be a high priority for health care systems to optimize health in clinicians to enhance high-quality care and decrease the odds of costly preventable medical errors.

Importance Otitis media (OM) is a leading cause of pediatric healthcare visits and the most frequent reason children consume antibiotics or undergo surgery. During recent years, several interventions have been introduced aiming to decrease OM burden. Objective To study the trend in OM-related healthcare utilization in the United States, during the pneumococcal conjugated vaccine (PCV) era (2001-2011). Design and Participants Analysis of an insurance claims database of a large, nationwide managed healthcare plan. Enrolled children ≤6 years with OM visit(s) were identified. Outcome measures Annual OM visit rates, OM-related complications and surgical interventions. Results Overall, 7.82 million unique children (5.51 million child-years) contributed 6.21 million primary OM visits; 52% were boys, and 48% were <2 years. There was a downward trend in OM visit rates from 2004-2011, with a significant drop that coincided with the advent of PCV-13 in 2010. The observed OM visit rates in 2010 (1.00/child-year) and 2011 (0.81) were lower than the projected rates, based on the 2005-2009 trend, had there been no intervention (P<0.001). Recurrent OM (≥3 OM within 6 months look-back) rates decreased at 0.003/ child-year in 2001-2009 (95% CI=0.002-0.004) and at 0.018/child-year in 2010-2011 (0.008-0.028). In the PCV-13 pre-market years, there was stable rate ratio (RR) between OM visit rates in children aged <2 years and of those aged 2-6 years (RRs=1.38; 95% CI: 1.38-1.39); RR decreased significantly (P<0.001), during the transition year 2010 (RR=1.32; 95% CI: 1.31-1.33) and the post-market year 2011 (RR =1.01; 95%; CI: 1.00-1.02). Tympanic membrane (TM) perforation/otorrhea rates gradually increased (from 3,721/100,000 OM child-years in 2001 to 4,542 in 2011; P<0.001); the increase was significant only in the older children group. Mastoiditis rates substantially decreased (from 61/100,000 child-years in 2008 to 37 in 2011; P<0.001). Ventilating tube insertion rate decreased by 19% from 2010 to 2011 (P=0.03). Conclusions There was an overall downward trend in OM-related healthcare utilization from 2001-2011. The significant reduction in OM visit rates in 2010-2011 in children <2 years coincided with the advent of PCV-13. While TM perforation/otorrhea rates steadily increased, mastoiditis and ventilating tube insertion rates decreased in the last years of the study.

Objective Chronic pain is a common neurological comorbidity of HIV-1 infection, but the etiological cause remains elusive. The objective of this study was to identify the HIV-1 causal factor that critically contributes to the pathogenesis of HIV-associated pain. Methods We first compared the levels of HIV-1 proteins in postmortem tissues of the spinal cord dorsal horn (SDH) from HIV-1/AIDS patients who developed chronic pain (‘pain-positive’ HIV-1 patients) and HIV-1 patients who did not develop chronic pain (‘pain-negative’ HIV-1 patients). Then, we used the HIV-1 protein that was specifically increased in the ‘pain-positive’ patients to generate mouse models. Finally, we performed comparative analyses on the pathological changes in the models and the HIV-1 patients. Results We found that HIV-1 gp120 was significantly higher in ‘pain-positive’ HIV-1 patients (vs. ‘pain-negative’ HIV-1 patients). This finding suggested that gp120 was a potential causal factor of the HIV-associated pain. To test this hypothesis, we used a mouse model generated by intrathecal injection (i.t.) of gp120 and compared the pathologies of the model and the ‘pain-positive’ human HIV-1 patients. The results showed that the mouse model and ‘pain-positive’ human HIV-1 patients developed extensive similarities in their pathological phenotypes, including pain behaviors, peripheral neuropathy, glial reactivation, synapse degeneration and aberrant activation of pain-related signaling pathways in the SDH. Interpretation Our findings suggest that gp120 may critically contribute to the pathogenesis of HIV-associated pain.

ObjectiveMany patients with irritable bowel syndrome IBS not only have abdominal pain but also may suffer from visceral hypersensitivity and heighted visceral nociception. Moreover, IBS has few effective therapeutic agents and mechanisms of disease are unclear. Our goals were to (i) identify microRNA (miRNA) expression, signalling and targets in human colon (controls; patients with IBS); (ii) verify in vitro, IBS-associated changes in miRNAs, especially miR-199, which is complementary to the transient receptor potential vanilloid type 1 (TRPV1) gene; and (iii) determine whether modulating the expression of miRNAs in vivo, especially miR-199, reverses associated changes and pathological hallmarks of visceral hypersensitivity via TRPV1 signalling.DesignWe evaluated 45 patients with diarrhoea-predominant IBS (IBS-D) and 40 controls with (1) visceral pain severity score and (2) colonoscopy with biopsies. miRNA expression was evaluated in human colon following miRNA array analysis. Luciferase assays were done to confirm relationships between miR-199 and TRPV1 expression. A rat model of visceral hypersensitivity was used to study miR-199 and its target gene (TRPV1) expression in dorsal root ganglion (DRG) and colon in vivo.ResultsGut miR-199a/b expression in IBS-D was significantly decreased, which correlated directly with both increased visceral pain scores and TRPV1 expression. In vivo upregulation of miR-199a by intraperitoneal injection of lenti-miR-199a precursors decreased visceral hypersensitivity via diminished TRPV1 signalling.ConclusionsDecreased colonic miR-199a/b correlates with visceral pain in patients with IBS-D. Similarly, reduced miR-199a expression in rat DRG and colon tissue is associated with heightened visceral hypersensitivity. In vivo upregulation of miR-199a decreases visceral pain via inhibition of TRPV1 signalling. Thus, miR-199 precursors may be promising therapeutic candidates for the treatment in patients with visceral pain.

Colorectal cancer is the second leading cause of death from cancer in the United States. Metastases in the liver, the most common metastatic site for colorectal cancer, are found in one-third of the patients who die of colorectal cancer. Currently, the genes and molecular mechanisms that are functionally critical in modulating colorectal cancer hepatic metastasis remain unclear. Here, we report our studies using functional selection in an orthotopic mouse model of colorectal cancer to identify a set of genes that play an important role in mediating colorectal cancer liver metastasis. These genes included APOBEC3G, CD133, LIPC, and S100P. Clinically, we found these genes to be highly expressed in a cohort of human hepatic metastasis and their primary colorectal tumors, suggesting that it might be possible to use these genes to predict the likelihood of hepatic metastasis. We have further revealed what we believe to be a novel mechanism in which APOBEC3G promotes colorectal cancer hepatic metastasis through inhibition of miR-29-mediated suppression of MMP2. Together, our data elucidate key factors and mechanisms involved in colorectal cancer liver metastasis, which could be potential targets for diagnosis and treatment. IntroductionAfter lymph nodes, the liver is the most common site for colorectal cancer metastasis, and liver metastasis is a common cause of cancer-related mortality (1-4). Most colorectal cancer patients with hepatic metastasis are not candidates for surgical treatment, and their 5-year survival rate following diagnosis of hepatic metastasis is below 10% (2, 4). It is well established that 5-year survival rates exceed 90% in patients diagnosed with early stage colorectal cancer (5, 6). It is imperative that we uncover the underlying mechanisms and genetic alterations that predispose to the metastatic phenotype in colorectal cancer. Such an understanding has the potential to improve early detection and prevention in addition to helping with developing novel targeted therapies for late stage disease. Studies reveal that genomic instability in cancer cells leads to cellular heterogeneity, which may guide tumor cell aggression and specific organ colonization during the metastatic process (7,8). Many studies have attempted to identify the metastasis-related genes in

Background Critical care nurses experience higher rates of mental distress and poor health than other nurses, adversely affecting health care quality and safety. It is not known, however, how critical care nurses’ overall health affects the occurrence of medical errors. Objective To examine the associations among critical care nurses’ physical and mental health, perception of workplace wellness support, and self-reported medical errors. Methods This survey-based study used a cross-sectional, descriptive correlational design. A random sample of 2500 members of the American Association of Critical-Care Nurses was recruited to participate in the study. The outcomes of interest were level of overall health, symptoms of depression and anxiety, stress, burnout, perceived worksite wellness support, and medical errors. Results A total of 771 critical care nurses participated in the study. Nurses in poor physical and mental health reported significantly more medical errors than nurses in better health (odds ratio [95% CI]: 1.31 [0.96-1.78] for physical health, 1.62 [1.17-2.29] for depressive symptoms). Nurses who perceived that their worksite was very supportive of their well-being were twice as likely to have better physical health (odds ratio [95% CI], 2.16 [1.33-3.52]; 55.8%). Conclusion Hospital leaders and health care systems need to prioritize the health of their nurses by resolving system issues, building wellness cultures, and providing evidence-based wellness support and programming, which will ultimately increase the quality of patient care and reduce the incidence of preventable medical errors.