Implementation fidelity of the 'Stay One Step Ahead' home safety intervention: a mixed-methods analysis.

OBJECTIVE: To assess implementation fidelity of the Stay One Step Ahead (SOSA), a complex intervention which was delivered by health visiting teams, children's centres, and family mentors and was aimed at preventing unintentional home injuries in children under 5 in disadvantaged communities. STUDY DESIGN: A mixed-methods evaluation of the implementation fidelity of the SOSA intervention. METHODS: A conceptual framework for implementation fidelity was used to triangulate data from questionnaires and semistructured interviews with parents and practitioners, observations of parent and practitioner contacts, and meeting documents. Quantitative data were analysed using logistic regression and descriptive statistics. Thematic analysis was used for qualitative data. RESULTS: Parents in intervention wards were more likely to receive home safety advice from a practitioner than those living in matched control wards. Monthly safety messages and family mentor home safety activities were delivered with greater fidelity than other intervention components. Content most frequently adapted included the home safety checklist used by health visiting teams, and safety weeks delivered at children's centres. CONCLUSION: Consistent with similarly complex interventions, SOSA was delivered with variable fidelity in a challenging environment. The findings add to the body of evidence on implementation fidelity of home injury prevention programmes, providing important information for future intervention development and delivery.

A Photo-responsive Small-Molecule Approach for the Opto-epigenetic Modulation of DNA Methylation.

Controlling the functional dynamics of DNA within living cells is essential in biomedical research. Epigenetic modifications such as DNA methylation play a key role in this endeavour. DNA methylation can be controlled by genetic means. Yet there are few chemical tools available for the spatial and temporal modulation of this modification. Herein, we present a small-molecule approach to modulate DNA methylation with light. The strategy uses a photo-tuneable version of a clinically used drug (5-aza-2'-deoxycytidine) to alter the catalytic activity of DNA methyltransferases, the enzymes that methylate DNA. After uptake by cells, the photo-regulated molecule can be light-controlled to reduce genome-wide DNA methylation levels in proliferating cells. The chemical tool complements genetic, biochemical, and pharmacological approaches to study the role of DNA methylation in biology and medicine.

Index Admission Emergency Laparoscopic Cholecystectomy and Common Bile Duct Exploration: Results From a Specialist Center in the United Kingdom.

BACKGROUND: The incidence of common bile duct (CBD) stones is between 10% to 18% in people undergoing cholecystectomy for gallstones. Laparoscopic exploration of the CBD is now becoming routine practice in the elective setting, however its safety and efficacy in emergencies is poorly understood. METHODS: We analyzed our results for index emergency admission laparoscopic cholecystectomy within a specialist center in the United Kingdom. Data from all emergency cholecystectomies in our unit, between 2011 to 2016 were collected and analyzed retrospectively. RESULTS: In total, 494 patients underwent emergency laparoscopic cholecystectomy; 53 (10.7%) patients underwent common bile duct exploration (CBDE), with 1 conversion and 1 bile leak. Indications for CBDE were based on preoperative imaging (41 cases, 81%) or intra-operative cholangiogram (44 cases, 83%) findings. CONCLUSIONS: Index admission laparoscopic cholecystectomy and concomitant CBDE is safe and should be the gold standard treatment for patients presenting with acute biliary complications, reducing readmissions and the need for a 2-stage procedure.

Experiences and Perspectives on Advance Care Planning among Individuals Living with Serious Physical Disabilities.

BACKGROUND: Despite frequent encounters with the healthcare system and high risk for secondary conditions, it is unclear how frequently individuals living with serious physical disabilities document advance directives (AD) or engage in advance care planning (ACP). Their perspectives on these topics are largely unknown. OBJECTIVE: We aimed to characterize the perspectives of individuals with serious physical disabilities receiving care from two different healthcare delivery settings on the value of AD and ACP. DESIGN: Key informant interviews were conducted, audiorecorded, transcribed, and analyzed using thematic analysis and constant comparative analysis. SUBJECTS: Twenty-five adults with serious physical disabilities were interviewed. RESULTS: Five organizing themes emerged as follows: (A) AD is a right versus responsibility, (B) past medical experiences influence ACP engagement, (C) ACP requires relationship-centered decision support, (D) concerns for care after death, and (E) suggestions for improving ACP experiences. Participants wished to engage in a relationship-centered approach to ACP, yet voiced hesitation due to experiences of significant medical bias and mistreatment, typically surrounding judgments of their quality of life. CONCLUSIONS: Better health professional training in ACP and heightened awareness of the unique ACP considerations pertaining to people with disabilities are recommended.

Patients with Ulcerative Colitis Are More Concerned About Complications of Their Disease than Side Effects of Medications.

BACKGROUND: Patients with ulcerative colitis (UC) are often fearful about medication side effects and how the disease will affect their future. Our aim was to better understand what aspects of UC, and UC management, are most concerning to patients, and how they would like to be informed about treatment options. METHODS: A Web-based survey was sent to UC patients throughout the United States and Australia. In addition to standard closed-response questions, audio clips were embedded in the survey and respondents showed their strength of agreement or disagreement using moment-to-moment affect-trace methodology. Standard quantitative analysis was used for the survey results, and cluster analysis was performed on the affect-trace responses. RESULTS: A total of 460 patients with UC (370 patients from the United States and 90 patients from Australia) responded to the survey. Of them, 53% of the respondents were women, with a mean age of 49 (range 19-81) years. Most patients (87%) wanted to share treatment decision making with their doctors. The majority, 98%, wanted more than just a basic understanding of their disease. Patients were most concerned about the risk of colorectal cancer (37%), and the possible need for an ileostomy (29%). Only 14% of patients indicated that side effects from medications were their biggest concern. On affect-trace analysis, the most divergence in opinion centered on the appropriate timing for colectomy. CONCLUSIONS: To facilitate informed treatment decisions for UC patients, in addition to reviewing the benefits and risks of medications, it is also important to discuss the best strategies for decreasing the risk of colectomy and colorectal cancer.

Patient Decision Control and the Use of Cardiac Catheterization.

BACKGROUND: Shared decision-making is a key determinant of patient-centered care. A lack of patient involvement in treatment decisions may explain persistent racial disparities in rates of cardiac catheterization (CCATH). To date, limited evidence exists to demonstrate whether patients who engage in shared decision-makingare more or less likely to undergo non-emergency CCATH. OBJECTIVE: To assess the relationship between participation in the decision to undergo a CCATH and the use of CCATH. We also examined whether preference for or actual engagement in decision-making varied by patient race. METHODS: We analyzed data from 826 male Veterans Administration patients for whom CCATH was indicated and who participated in the Cardiac Decision Making Study. RESULTS: After controlling for confounders, patients reporting any degree of decision control were more likely to receive CCATH compared with those reporting no control (doctor made decision without patient input) (54% vs 39%, P<.0001). Across racial groups, patients were equally likely to report a preference for control over decision-making (P=.53) as well as to experience discordance between their preference for control and their perception of the actual decision-making process (P=.59). Therefore, these factors did not mediate racial disparities in rates of CCATH use. CONCLUSION: Shared decision-making is an essential feature of whole-person care. While participation in decision-making may not explain disparities in CCATH rates, further work is required to identify strategies to improve congruence between patients' desire for and actual control over decision-making to actualize patient-centered care.

Design and rationale for a randomized controlled trial to reduce readmissions among patients with depressive symptoms.

BACKGROUND: The Re-Engineered Discharge (Project RED) reduces 30-day readmission rates by 30%. However, our data indicates that for patients displaying depressive symptoms during hospitalization, Project RED is less effective in preventing unplanned readmission. We aim to examine the effectiveness of RED-D, a modified brief Cognitive behavioral therapy (CBT) protocol delivered as a post-discharge extension of the Re-Engineered Discharge, in reducing 30-day readmissions rates and emergency department (ED) use as well as depressive symptoms for medical patients with comorbid depressive symptoms. METHODS: This paper details the study design and implementation of an ongoing, federally funded randomized controlled trial of our post-discharge mental health intervention, RED-D, compared to the RED plus usual care. This research has two primary objectives: (1) to determine whether RED-D delivered telephonically by a mental health professional immediately following discharge is effective in reducing hospital readmission and emergency department use for patients displaying depressive symptoms during their inpatient stay, and (2) to examine whether this approach yields a clinically significant reduction in depressive symptoms. We intend to recruit 1200 participants randomized to our intervention, RED-D (n=600), and to RED plus usual care (n=600). CONCLUSIONS: Hospitalized patients with depressive symptoms are at increased risk for 30-day readmission. We aim to conduct a randomized clinical trial to evaluate the comparative effectiveness of RED-D, our post-discharge modified brief CBT intervention compared to RED alone in reducing readmissions and depressive symptoms for this at-risk population.

Accurate measurement of 5-methylcytosine and 5-hydroxymethylcytosine in human cerebellum DNA by oxidative bisulfite on an array (OxBS-array).

The Infinium 450K Methylation array is an established tool for measuring methylation. However, the bisulfite (BS) reaction commonly used with the 450K array cannot distinguish between 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). The oxidative-bisulfite assay disambiguates 5mC and 5hmC. We describe the use of oxBS in conjunction with the 450K array (oxBS-array) to analyse 5hmC/5mC in cerebellum DNA. The "methylation" level derived by the BS reaction is the combined level of 5mC and 5hmC at a given base, while the oxBS reaction gives the level of 5mC alone. The level of 5hmC is derived by subtracting the oxBS level from the BS level. Here we present an analysis method that distinguishes genuine positive levels of 5hmC at levels as low as 3%. We performed four replicates of the same sample of cerebellum and found a high level of reproducibility (average r for BS = 98.3, and average r for oxBS = 96.8). In total, 114,734 probes showed a significant positive measurement for 5hmC. The range at which we were able to distinguish 5hmC occupancy was between 3% and 42%. In order to investigate the effects of multiple replicates on 5hmC detection we also simulated fewer replicates and found that decreasing the number of replicates to two reduced the number of positive probes identified by > 50%. We validated our results using qPCR in conjunction with glucosylation of 5hmC sites followed by MspI digestion and we found good concordance with the array estimates (r = 0.94). This experiment provides a map of 5hmC in the cerebellum and a robust dataset for use as a standard in future 5hmC analyses. We also provide a novel method for validating the presence of 5hmC at low levels, and highlight some of the pitfalls associated with measuring 5hmC and 5mC.

oxBS-450K: a method for analysing hydroxymethylation using 450K BeadChips.

DNA methylation analysis has become an integral part of biomedical research. For high-throughput applications such as epigenome-wide association studies, the Infinium HumanMethylation450 (450K) BeadChip is currently the platform of choice. However, BeadChip processing relies on traditional bisulfite (BS) based protocols which cannot discriminate between 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). Here, we report the adaptation of the recently developed oxidative bisulfite (oxBS) chemistry to specifically detect both 5mC and 5hmC in a single workflow using 450K BeadChips, termed oxBS-450K. Supported by validation using mass spectrometry and pyrosequencing, we demonstrate reproducible (R(2)>0.99) detection of 5hmC in human brain tissue using the optimised oxBS-450K protocol described here.