Soft X-ray microscopy for probing of topical tacrolimus delivery via micelles.

The penetration of topically applied tacrolimus formulated in micelles into murine skin is reported, measured by X-ray microscopy. Tacrolimus and micelles are probed for the first time by this high spatial resolution technique by element-selective excitation in the C 1s- and O 1s-regimes. This method allows selective detection of the distribution and penetration depth of drugs and carrier molecules into biologic tissues. It is observed that small, but distinct quantities of the drug and micelles, acting as a drug carrier, penetrate the stratum corneum. A comparison is made with the paraffin-based commercial tacrolimus ointment Protopic®, where local drug concentrations show to be low. A slight increase in local drug concentration in the stratum corneum is observed, if tacrolimus is formulated in micelles, as compared to Protopic®. This underscores the importance of the drug formulations for effective drug delivery. Time-resolved penetration shows presence of drug in the stratum corneum 100 min after formulation application, with penetration to deeper skin layers at 1000 min. High resolution micrographs give indications for a penetration pathway along the lipid membranes between corneocytes, but also suggest that the compound may penetrate corneocytes.

A Review of Studies on the System-Wide Implementation of Evidence-Based Psychotherapies for Posttraumatic Stress Disorder in the Veterans Health Administration.

Since 2006, the Veterans Health Administration (VHA) has instituted policy changes and training programs to support system-wide implementation of two evidence-based psychotherapies (EBPs) for posttraumatic stress disorder (PTSD). To assess lessons learned from this unprecedented effort, we used PubMed and the PILOTS databases and networking with researchers to identify 32 reports on contextual influences on implementation or sustainment of EBPs for PTSD in VHA settings. Findings were initially organized using the exploration, planning, implementation, and sustainment framework (EPIS; Aarons et al. in Adm Policy Ment Health Health Serv Res 38:4-23, 2011). Results that could not be adequately captured within the EPIS framework, such as implementation outcomes and adopter beliefs about the innovation, were coded using constructs from the reach, effectiveness, adoption, implementation, maintenance (RE-AIM) framework (Glasgow et al. in Am J Public Health 89:1322-1327, 1999) and Consolidated Framework for Implementation Research (CFIR; Damschroder et al. in Implement Sci 4(1):50, 2009). We highlight key areas of progress in implementation, identify continuing challenges and research questions, and discuss implications for future efforts to promote EBPs in large health care systems.

Uniaxial ferroelectric quantum criticality in multiferroic hexaferrites BaFe12O19 and SrFe12O19.

BaFe12O19 is a popular M-type hexaferrite with a Néel temperature of 720 K and is of enormous commercial value ($3 billion/year). It is an incipient ferroelectric with an expected ferroelectric phase transition extrapolated to lie at 6 K but suppressed due to quantum fluctuations. The theory of quantum criticality for such uniaxial ferroelectrics predicts that the temperature dependence of the electric susceptibility χ diverges as 1/T(3), in contrast to the 1/T(2) dependence found in pseudo-cubic materials such as SrTiO3 or KTaO3. In this paper we present evidence of the susceptibility varying as 1/T(3), i.e. with a critical exponent γ = 3. In general γ = (d + z - 2)/z, where the dynamical exponent for a ferroelectric z = 1 and the dimension is increased by 1 from deff = 3 + z to deff = 4 + z due to the effect of long-range dipole interactions in uniaxial as opposed to multiaxial ferroelectrics. The electric susceptibility of the incipient ferroelectric SrFe12O19, which is slightly further from the quantum phase transition is also found to vary as 1/T(3).

Predicting violent behavior in clinical settings: a case-control study of a mental health inpatient unit.

In order to assist staff in recognizing patients prone to violence and guide their clinical decision-making, this study summarizes mental health inpatient unit incidents over a one-year period. Results describe demographic and clinical information for patients, and evaluate risk assessment tools currently used to predict risk. A retrospective analysis included data on patients involved in incidents and frequency matched controls. There were a total of 44 incidents, caused by 38 unique patients. A constructed model to estimate patient characteristics and risk of violent incidents included involuntary admittance (OR 2.07, 95% CI 1.05-6.11, p = 0.039), more than one admission at the facility (OR 4.18, 95% CI 1.71-10.22, p = 0.002) and Global Subjective Irritability on day one (OR 4.24, 95% CI 1.77-10.16, p = 0.001). Violent incidents on the mental inpatient unit threaten safety and disrupt the therapeutic environment. The findings may be useful in aiding clinicians to quickly recognize patients that are prone to violence.

Suicide attempts and completions in Veterans Affairs nursing home care units and long-term care facilities: a review of root-cause analysis reports.

OBJECTIVE: Suicide was the 10th leading cause of death for Americans in 2010. The suicide rate is highest among men who are aged 75 and older. The prevalence of suicidal behavior in nursing homes and long-term care (LTC) facilities was estimated to be 1%. This study describes the systemic vulnerabilities found after suicidal behavior in LTC facilities as well as steps to decrease or mitigate the risk. METHOD: This is a retrospective review of root-cause analysis (RCA) reports of suicide attempts and completions between 1 January 2000 and 31 December 2013 in the Veterans Health Administration LTC and nursing home care units. The RCA reports of suicide attempts and completions were coded for patient demographics, method of attempt or completion, root causes, and actions developed to address the root cause. RESULTS: Thirty-five RCA reports were identified. The average age was 65 years, 11 had a previous suicide attempt, and the primary mental health diagnoses were depression, posttraumatic stress disorder, and schizophrenia. The primary methods of self-harm were cutting with a sharp object, overdose, and strangulation. CONCLUSIONS: It is recommended that all staff members are aware of the signs and risk factors for depression and suicide in this population and should systematically assess and treat mental disorders. In addition, LTC facilities should have a standard protocol for evaluating the environment for suicide hazards and use interdisciplinary teams to promote good communication about risk factors identified among patients. Finally, staff should go beyond staff education and policy to make clinical changes at the bedside. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

Suicide attempts and completions on medical-surgical and intensive care units.

Studies of inpatient suicide attempts and completions on medical-surgical and intensive care units are rare, and there are no large studies in the United States. We reviewed 50 cases, including 45 suicide attempts and 5 completed suicides, that occurred on medical surgical or intensive care units in the Veterans Health Administration between December 1, 1999 and December 31, 2012. The method, location, and the root causes of the events were categorized. The most common methods included cutting with a sharp object, followed by overdose and hanging. Root causes included problems with communication of risk, need for staff education in suicide assessment, and the need for better treatment for depressed and suicidal patients on medical units. Based on these results, we made our recommendations for managing suicidal patients on medical-surgical and intensive care units, including improved education for staff, standardized communication about suicide risk, and clear management protocols for suicidal patients.

Dental hygienists' knowledge of HIV, attitudes towards people with HIV and willingness to conduct rapid HIV testing.

OBJECTIVES: To normalize rapid human immunodeficiency virus (HIV) testing in the United States, expanded rapid HIV testing initiatives are needed outside the routine medical setting. The dental setting is a logical choice as almost two-thirds of Americans regularly see a dental provider each year. This study was aimed to determine the dental hygienists' knowledge of HIV, attitudes towards people living with HIV and willingness to conduct rapid HIV testing. METHODS: A national cross-sectional survey of practicing dental hygienists and senior dental hygiene students were recruited using state dental hygiene associations, email LISTSERVS, dental hygiene programmes and continuing education conferences (n = 634). RESULTS: The mean knowledge score was 10.5/13. High versus low test-scorers (75% of test questions or more answered correctly versus less than 75% answered correctly) did differ in their comfort level in counselling about sexual HIV prevention methods (P = 0.03) and comfort level in working with medically compromised patients (P = 0.04). CONCLUSION: Dental hygienists, with additional training in HIV prevention counseling and diagnostic testing, may be an appropriate profession to conduct rapid HIV testing.

A cross-sectional study on the relationship between utilization of root cause analysis and patient safety at 139 Department of Veterans Affairs medical centers.

BACKGROUND: Empirical evidence is limited that root cause analysis (RCA), an event analysis tool used in health care to evaluate the systemic factors that lead to adverse events, improves patient safety. A cross-sectional study was conducted to examine the relationship between RCA and patient safety. METHODS: RCA data were collected for the 139 Department of Veteran Affairs medical centers (VAMCs) in the National Center for Patient Safety database from 2004 through 2006. Participants were divided into three RCA utilization categories on the basis of their yearly RCA rate: (1) fewer than 4 RCAs, (2) 4 to 5 RCAs, and (3) 6 or more RCAs per year. An analysis of variance was conducted of each Agency for Healthcare Research and Quality Patient Safety Indicators (PSIs) across the three RCA utilization categories. RESULTS: Facilities completed between 3 and 59 RCAs in the three-year period (mean RCA utilization rate, 4.86 RCAs per year). In this period, RCA actions by facility ranged from 9 to 323 (mean, 28 actions per year per facility). Mean patient-days of care, facility budget, surgical volume, and the number of strong improvement actions were significantly different across RCA utilization categories. The mean rates of PSI 9 (Postoperative Hemorrhage or Hematoma), PSI 10 (Postoperative Physiologic and Metabolic Derangements), and PSI 13 (Postoperative Sepsis) were significantly different across RCA utilization categories. CONCLUSIONS: Large, high-spending VAMCs conduct more RCAs per year than smaller, low-spending facilities. VAMCs that do more RCAs develop more corrective actions. VAMCs that complete fewer than four RCAs per year have higher rates of postoperative complications. It is unclear if RCAs are associated with a functional patient safety program or directly improve patient safety.

Suicide attempts and completions in the emergency department in Veterans Affairs Hospitals.

BACKGROUND: This is the first study of suicide attempts and completions in the emergency department (ED) in a large national medical system. METHODS: All root cause analysis (RCA) reports completed of suicides and suicide attempts that occurred in ED in the Veterans Health Administration between 1 December 1999 and 31 December 2009 were reviewed. The method, location, anchor point for hanging and implement for cutting as well as the root causes were categorised. RESULTS: Ten per cent of all RCA reports of suicides and suicide attempts that occur within the hospital occur in the ED. Hanging, cutting and strangulation were the most common methods. The most common anchor point for hanging was doors, and the most common implement for cutting was a razor blade. In eight of the 10 cases of cutting, the implement was brought into the ED. The most common root causes were problems communicating risk and being short-staffed. CONCLUSIONS: Based on these results the following recommendations are made for helping to reduce suicide attempts in the ED: (1) use a systematic protocol and checklist to review mental health holding areas periodically in the ED for suicidal hazards; (2) develop and implement specialised protocols for suicidal patients that include continuous observation when possible; (3) conduct thorough contraband searches with suicidal patients; (4) designate specialised holding areas, when practically possible, for suicidal patients that are free of anchor points for hanging, sharps and medications, and medical equipment; and are isolated from exits to reduce the risk of elopement.

Calibrated NEXAFS spectra of common conjugated polymers.

Near edge x-ray absorption fine structure (NEXAFS) spectroscopy has evolved into a powerful characterization tool for polymeric materials and is increasingly being used to elucidate composition and orientation in thin films of relevance to organic electronic devices. For accurate quantitative compositional analysis, insight into the electronic structure and the ability to assess molecular orientation, reliable reference spectra with known energy resolution and calibrated energy scale are required. We report a set of such NEXAFS spectra from 23 semiconducting polymers and some related materials that are frequently used in organic device research.

Improving depression care in a psychiatry resident psychopharmacology clinic: measurement, monitoring, feedback and education.

OBJECTIVE: Better outcomes for major depressive disorder (MDD) are associated with proactive treatment, including timely follow-up, systematic assessment and treatment changes for inadequate improvement. The effectiveness of an intervention to facilitate proactive treatment for MDD in a resident psychopharmacology clinic was studied. METHODS: A quality improvement program with administrative process changes to improve flow and a 40-week pre/post study to evaluate the effect of education and feedback was conducted. A systematic assessment and reengineered scheduling system were implemented. During the first 20 weeks, baseline data were collected; during the second 20 weeks, feedback to residents and attending psychiatrists about adherence to evidence-based treatment recommendations was added. RESULTS: Reengineering our system to improve flow was successful. By linking outcomes collection to completion of billing sheets, outcomes at 90% of visits for MDD throughout the 40-week study was assessed. By centralising our scheduling system, the percentage of active-phase patients with MDD seen for follow-up within 6 weeks was improved from 19% to 59%. In response to feedback, residents did not make significant changes to their overall practice patterns. Patient outcomes did not improve as a result of feedback to residents. Residents did improve their practice patterns for a subset of patients including those without comorbid psychiatric disorders and those whose depressive episodes had lasted <1 year. CONCLUSIONS: Improving administrative processes for the treatment of patients with MDD resulted in rapid changes that were associated with improvements in the delivery of evidence-based care. Feedback to residents was more difficult and less successful.

A checklist to identify inpatient suicide hazards in veterans affairs hospitals.

BACKGROUND: Approximately 1,500 suicides take place in inpatient hospital units in the United States each year. This study, the first of its kind, examines the implementation and effectiveness of using a standardized checklist for mental health units to improve patient safety in a large health care system. METHODS: In 2006 a Department of Veterans Affairs (VA) committee was charged with developing a checklist to explicitly identify environmental hazards on acute mental health units treating suicidal patients. The committee developed both general guidelines to be applied to all areas of the psychiatric unit and detailed guidelines for specific rooms, such as bathrooms, bedrooms, and seclusion rooms. RESULTS: Some 113 VA facilities used the Mental Health Environment of Care Checklist to evaluate their mental health units, identifying and rating 7,642 hazards. At the end of the first year of the project, because of the checklist, 5,834 (76.3%) of these hazards had been abated by facilities; approximately 2% were identified as critical hazards, and another 27% were rated as serious. The most common hazard was anchor points for hanging, followed by material that could be used as a weapon against staff or other patients and problems keeping patients in the secured unit environment. Anchor points had the greatest risk-level classification, followed by suffocation risk and poison risk. High-risk locations included bedrooms and bathrooms. DISCUSSION: Anchor points represented almost 44% of the total number of identified hazards, and materials that could be used as weapons comprised nearly 14% of the total. It is critical to review the mental health environment of care with an eye for these potential weapons. The checklist and resulting mitigations of hazards represent steps toward the overall goal of preventing inpatient suicides.

Pre-hospital use of ketamine for analgesia and procedural sedation.

The safe delivery of adequate analgesia and appropriate sedation is a priority in prehospital care. The use of ketamine is described for analgesia and sedation in 1030 trauma patients in a physician-led prehospital trauma service. Ketamine was mainly used in awake non-trapped patients with blunt trauma for procedural sedation and analgesia. Detailed database searches did not demonstrate loss of airway, oxygen desaturation or clinically significant emergence reactions after ketamine administration. Ketamine is relatively safe when used by physicians in prehospital trauma care.

The SQUIRE (Standards for QUality Improvement Reporting Excellence) guidelines for quality improvement reporting: explanation and elaboration.

As the science of quality improvement in health care advances, the importance of sharing its accomplishments through the published literature increases. Current reporting of improvement work in health care varies widely in both content and quality. It is against this backdrop that a group of stakeholders from a variety of disciplines has created the Standards for QUality Improvement Reporting Excellence, which we refer to as the SQUIRE publication guidelines or SQUIRE statement. The SQUIRE statement consists of a checklist of 19 items that authors need to consider when writing articles that describe formal studies of quality improvement. Most of the items in the checklist are common to all scientific reporting, but virtually all of them have been modified to reflect the unique nature of medical improvement work. This "Explanation and Elaboration" document (E & E) is a companion to the SQUIRE statement. For each item in the SQUIRE guidelines the E & E document provides one or two examples from the published improvement literature, followed by an analysis of the ways in which the example expresses the intent of the guideline item. As with the E & E documents created to accompany other biomedical publication guidelines, the purpose of the SQUIRE E & E document is to assist authors along the path from completion of a quality improvement project to its publication. The SQUIRE statement itself, this E & E document, and additional information about reporting improvement work can be found at http://www.squire-statement.org.

The effectiveness of root cause analysis: what does the literature tell us?

BACKGROUND: Root cause analysis (RCA) is an analysis framework used in health care to determine the systemic causes and prevent recurrences of adverse events. It is required by The Joint Commission for reported events and by the Department of Veterans Affairs (VA) National Center for Patient Safety for qualifying events in VA medical centers. The evidence on RCA effectiveness in improving patient safety was reviewed. METHODS: MEDLINE, Academic Search Premier, and the Cochrane Database were searched from database inception to September 2007. RCA case studies and articles that directly addressed the RCA framework were reviewed. RESULTS: Discussion of RCA did not emerge in the literature until the late 1990s, and there have been no controlled trials that test the RCA framework. Twenty-three articles describe the RCA process, 38 articles present RCA case studies, and 12 articles analyze weaknesses of the RCA framework. Eleven of the case studies measure RCA effectiveness, 3 using clinical outcome measures and 8 using process measures. All 11 articles report improvement of safety following RCA. RCA participants report the difficulty in forming causal statements and in developing/implementing corrective actions. Criticisms of RCA include the uncontrolled study design and participant biases. DISCUSSION: Overall, the limited literature on RCA effectiveness provides anecdotal evidence that RCA improves safety. At the same time, it highlights the numerous theoretical problems with the analytical framework. Formal studies at the system level and cost-benefit analysis are needed to determine the effectiveness of RCA. Structured publication of case studies will support shared knowledge and will provide benchmarks for improvement. Enrichment of the RCA literature body will enable reproducibility of improvement work, optimization of analysis, and validation of the framework itself.

Evolution of the nanomorphology of photovoltaic polyfluorene blends: sub-100 nm resolution with x-ray spectromicroscopy.

We investigate the influence of annealing on the morphology of intimately mixed blends of the conjugated polymers poly(9,9'-dioctylfluorene-co-bis-N,N'-(4-butylphenyl)-bis-N,N'-phenyl-1,4-phenylene-diamine) (PFB) and poly(9,9'-dioctylfluorene-co-benzothiadiazole) (F8BT) with scanning transmission x-ray microscopy (STXM). Through the use of a zone plate with theoretical Rayleigh resolution of 30 nm, we are able to resolve sub-100 nm bulk structure in these films. Surprisingly, for unannealed films spin-coated from chloroform we observe features with an average diameter of 85 nm. The high degree of photoluminescence quenching in these as-spun films (>95%) implies that there is significant intermixing within the 85 nm structures, indicating that a hierarchy of phase separation exists even on the length scale of less than 100 nm. With annealing up to 160 °C, close to the T(g) of the components, there is little change in the feature sizes observed by STXM, although an increase in variation of the composition is observed. With annealing above 160 °C the imaged features begin to evolve in size, increasing to 225 nm in extent, alongside large changes in composition with annealing to 200 °C. Comparing the evolution of morphology imaged by STXM with the change in photoluminescence quenching with annealing, we propose that phase separation first evolves via the evolution of relatively pure phases on the length scale of a few to tens of nanometres within the larger 85 nm structures. Once the length scale of compositional fluctuations exceeds 85 nm (for anneal temperatures above 160 °C) the hierarchy of phase separation is lost and the subsequent morphological evolution is readily imaged by STXM. Applying the results of an exciton diffusion and quenching model, we find good agreement between the size of the domains measured by STXM (above 180 °C) and the results of the model for an exciton diffusion length of 15 nm. The growth in domain size and towards purer structures has also been observed with resonant soft x-ray scattering.

A randomised controlled trial to determine the effectiveness of double Tubigrip in grade 1 and 2 (mild to moderate) ankle sprains.

OBJECTIVE: To compare functional outcome in patients with acute grade 1 or 2 (mild to moderate) lateral ankle sprains randomised to treatment with or without a double tubigrip bandage (DTG). METHODS: 400 patients presenting to the accident and emergency (A&E) departments of a teaching hospital and a district general hospital and diagnosed with grade 1 or 2 lateral ankle sprains were randomised to treatment with or without a DTG bandage. A standardised telephone questionnaire was performed one week after presentation. The main outcome measures were: number of days until walking unaided, number of days off work, whether the injury kept the patient awake at night, whether analgesia was taken. RESULTS: 197 of 400 patients completed follow up. There were no significant differences in terms of age, sex and occupation between the treatment groups. There were no significant differences between those who did and those who did not complete follow up. There was no significant difference between the treatment groups for number of days until walking unaided (95% CI -0.21 to 0.88 days), number of days off work (95% CI -0.70 to 1.02 days) or whether the injury kept the patient awake at night (95% CI -10 to 17%). There was a significant difference between the groups in the use of analgesia (95% CI 10 to 36%); the difference seemed to be that patients treated with DTG required significantly more analgesia. CONCLUSIONS: Treatment of grade 1 and 2 ankle sprins with DTG does not seem to lead to a shorter time to functional recovery and may increase the requirement for analgesia.

Hyposmolality stimulates Na(+)/H(+) exchange and HCO(3)(-) absorption in thick ascending limb via PI 3-kinase.

The signal transduction mechanisms that mediate osmotic regulation of Na(+)/H(+) exchange are not understood. Recently we demonstrated that hyposmolality increases HCO(3)(-) absorption in the renal medullary thick ascending limb (MTAL) through stimulation of the apical membrane Na(+)/H(+) exchanger NHE3. To investigate the mechanism of this stimulation, MTALs from rats were isolated and perfused in vitro with 25 mM HCO(3)(-)-containing solutions. The phosphatidylinositol 3-kinase (PI 3-K) inhibitors wortmannin (100 nM) and LY-294002 (20 microM) blocked completely the stimulation of HCO(3)(-) absorption by hyposmolality. In tissue strips dissected from the inner stripe of the outer medulla, the region of the kidney highly enriched in MTALs, hyposmolality increased PI 3-K activity 2. 2-fold. Wortmannin blocked the hyposmolality-induced PI 3-K activation. Further studies examined the interaction between hyposmolality and vasopressin, which inhibits HCO(3)(-) absorption in the MTAL via cAMP and often is involved in the development of plasma hyposmolality in clinical disorders. Pretreatment with arginine vasopressin, forskolin, or 8-bromo-cAMP abolished hyposmotic stimulation of HCO(3)(-) absorption, due to an effect of cAMP to inhibit hyposmolality- induced activation of PI 3-K. In contrast to their effects to block stimulation by hyposmolality, PI 3-K inhibitors and vasopressin have no effect on inhibition of apical Na(+)/H(+) exchange (NHE3) and HCO(3)(-) absorption by hyperosmolality. These results indicate that hyposmolality increases NHE3 activity and HCO(3)(-) absorption in the MTAL through activation of a PI 3-K-dependent pathway that is inhibited by vasopressin and cAMP. Hyposmotic stimulation and hyperosmotic inhibition of NHE3 are mediated through different signal transduction mechanisms.