Determination of Factors Associated with Upstage in Atypical Ductal Hyperplasia to Identify Low-Risk Patients Where Active Surveillance May be an Alternative.

BACKGROUND: Excision is routinely recommended for atypical ductal hyperplasia (ADH) found on core biopsy given cancer upstage rates of near 20%. Identifying a cohort at low-risk for upstage may avoid low-value surgery. Objectives were to elucidate factors predictive of upstage in ADH, specifically near-complete core sampling, to potentially define a group at low upstage risk. PATIENTS AND METHODS: This retrospective, cross-sectional, multi-institutional study from 2015 to 2019 of 221 ADH lesions in 216 patients who underwent excision or active observation (≥ 12 months imaging surveillance, mean follow-up 32.6 months) evaluated clinical, radiologic, pathologic, and procedural factors for association with upstage. Radiologists prospectively examined imaging for lesional size and sampling proportion. RESULTS: Upstage occurred in 37 (16.7%) lesions, 25 (67.6%) to ductal carcinoma in situ (DCIS) and 12 (32.4%) to invasive cancer. Factors independently predictive of upstage were lesion size ≥ 10 mm (OR 5.47, 95% CI 2.03-14.77, p < 0.001), pathologic suspicion for DCIS (OR 12.29, 95% CI 3.24-46.56, p < 0.001), and calcification distribution pattern (OR 8.08, 95% CI 2.04-32.00, p = 0.003, "regional"; OR 19.28, 95% CI 3.47-106.97, p < 0.001, "linear"). Near-complete sampling was not correlated with upstage (p = 0.64). All three significant predictors were absent in 65 (29.4%) cases, with a 1.5% upstage rate. CONCLUSIONS: The upstage rate among 221 ADH lesions was 16.7%, highest in lesions ≥ 10 mm, with pathologic suspicion of DCIS, and linear/regional calcifications on mammography. Conversely, 30% of the cohort exhibited all low-risk factors, with an upstage rate < 2%, suggesting that active surveillance may be permissible in lieu of surgery.

HyCCAPP as a tool to characterize promoter DNA-protein interactions in Saccharomyces cerevisiae.

Currently available methods for interrogating DNA-protein interactions at individual genomic loci have significant limitations, and make it difficult to work with unmodified cells or examine single-copy regions without specific antibodies. In this study, we describe a physiological application of the Hybridization Capture of Chromatin-Associated Proteins for Proteomics (HyCCAPP) methodology we have developed. Both novel and known locus-specific DNA-protein interactions were identified at the ENO2 and GAL1 promoter regions of Saccharomyces cerevisiae, and revealed subgroups of proteins present in significantly different levels at the loci in cells grown on glucose versus galactose as the carbon source. Results were validated using chromatin immunoprecipitation. Overall, our analysis demonstrates that HyCCAPP is an effective and flexible technology that does not require specific antibodies nor prior knowledge of locally occurring DNA-protein interactions and can now be used to identify changes in protein interactions at target regions in the genome in response to physiological challenges.

Improving multidisciplinary communication at ward board rounds using video enhanced reflective practice.

The priority to ensure patient safety and use resources effectively, demands attention and innovation. Video enhanced reflective practice (VERP) provides training based upon analysis of film clips of one's professional practice to develop practical insight into the processes of communication, so that effective changes can be made to ongoing behaviour and practice. In this case the focus was on multi-disciplinary communication within daily board rounds on an acute medicine and care of the elderly ward. Baseline assessment and post intervention testing of perceptions of change by both full and core team were undertaken to establish the impact of VERP training. In addition pre and post focus group discussion and film analysis supplemented evaluation. The findings support the view that after VERP training of a core team, board rounds were seen as consistently easier to participate in, providing improved focus, were more efficient in goal setting and resulting in better care for patients as well as improved pathways to discharge. This suggests benefits to the communication "culture" of a multidisciplinary team resulting in increased benefits for the wider team. It is concluded that the use of tailored VERP training for personal, professional and team development is relevant, feasible, and worthy of further testing and investigation.

Explaining the uptake of paediatric guidelines in a Kenyan tertiary hospital--mixed methods research.

BACKGROUND: Evidence-based standards for management of the seriously sick child have existed for decades, yet their translation in clinical practice is a challenge. The context and organization of institutions are known determinants of successful translation, however, research using adequate methodologies to explain the dynamic nature of these determinants in the quality-of-care improvement process is rarely performed. METHODS: We conducted mixed methods research in a tertiary hospital in a low-income country to explore the uptake of locally adapted paediatric guidelines. The quantitative component was an uncontrolled before and after intervention study that included an exploration of the intervention dose-effect relationship. The qualitative component was an ethnographic research based on the theoretical perspective of participatory action research. Interpretive integration was employed to derive meta-inferences that provided a more complete picture of the overall study results that reflect the complexity and the multifaceted ontology of the phenomenon studied. RESULTS: The improvement in health workers' performance in relation to the intensity of the intervention was not linear and was characterized by improved and occasionally declining performance. Possible root causes of this performance variability included challenges in keeping knowledge and clinical skills updated, inadequate commitment of the staff to continued improvement, limited exposure to positive professional role models, poor teamwork, failure to maintain professional integrity and mal-adaptation to institutional pressures. CONCLUSION: Implementation of best-practices is a complex process that is largely unpredictable, attributed to the complexity of contextual factors operating predominantly at professional and organizational levels. There is no simple solution to implementation of best-practices. Tackling root causes of inadequate knowledge translation in this tertiary care setting will require long-term planning, with emphasis on promotion of professional ethics and values and establishing an organizational framework that enhances positive aspects of professionalism. This study has significant implications for the quality of training in medical institutions and the development of hospital leadership.

Factors influencing performance of health workers in the management of seriously sick children at a Kenyan tertiary hospital--participatory action research.

BACKGROUND: Implementation of World Health Organization case management guidelines for serious childhood illnesses remains a challenge in hospitals in low-income countries. Facilitators of and barriers to implementation of locally adapted clinical practice guidelines (CPGs) have not been explored. METHODS: This ethnographic study based on the theory of participatory action research (PAR) was conducted in Kenyatta National Hospital, Kenya's largest teaching hospital. The primary intervention consisted of dissemination of locally adapted CPGs. The PRECEDE-PROCEED health education model was used as the conceptual framework to guide and examine further reinforcement activities to improve the uptake of the CPGs. Activities focussed on introduction of routine clinical audits and tailored educational sessions. Data were collected by a participant observer who also facilitated the PAR over an eighteen-month period. Naturalistic inquiry was utilized to obtain information from all hospital staff encountered while theoretical sampling allowed in-depth exploration of emerging issues. Data were analysed using interpretive description. RESULTS: Relevance of the CPGs to routine work and emergence of a champion of change facilitated uptake of best-practices. Mobilization of basic resources was relatively easily undertaken while activities that required real intellectual and professional engagement of the senior staff were a challenge. Accomplishments of the PAR were largely with the passive rather than active involvement of the hospital management. Barriers to implementation of best-practices included i) mismatch between the hospital's vision and reality, ii) poor communication, iii) lack of objective mechanisms for monitoring and evaluating quality of clinical care, iv) limited capacity for planning strategic change, v) limited management skills to introduce and manage change, vi) hierarchical relationships, and vii) inadequate adaptation of the interventions to the local context. CONCLUSIONS: Educational interventions, often regarded as 'quick-fixes' to improve care in low-income countries, may be necessary but are unlikely to be sufficient to deliver improved services. We propose that an understanding of organizational issues that influence the behaviour of individual health professionals should guide and inform the implementation of best-practices.

Developing the specifications of an open angle glaucoma screening intervention in the United Kingdom: a Delphi approach.

BACKGROUND: Glaucoma is a leading cause of blindness. Early detection is advocated but there is insufficient evidence from randomized controlled trials (RCTs) to inform health policy on population screening. Primarily, there is no agreed screening intervention. For a screening programme, agreement is required on the screening tests to be used, either individually or in combination, the person to deliver the test and the location where testing should take place. This study aimed to use ophthalmologists (who were experienced glaucoma subspecialists), optometrists, ophthalmic nurses and patients to develop a reduced set of potential screening tests and testing arrangements that could then be explored in depth in a further study of their feasibility for evaluation in a glaucoma screening RCT. METHODS: A two-round Delphi survey involving 38 participants was conducted. Materials were developed from a prior evidence synthesis. For round one, after some initial priming questions in four domains, specialists were asked to nominate three screening interventions, the intervention being a combination of the four domains; target population, (age and higher risk groups), site, screening test and test operator (provider). More than 250 screening interventions were identified. For round two, responses were condensed into 72 interventions and each was rated by participants on a 0-10 scale in terms of feasibility. RESULTS: Using a cut-off of a median rating of feasibility of ≥5.5 as evidence of agreement of intervention feasibility, six interventions were identified from round 2. These were initiating screening at age 50, with a combination of two or three screening tests (varying combinations of tonometry/measures of visual function/optic nerve damage) organized in a community setting with an ophthalmic trained technical assistant delivering the tests. An alternative intervention was a 'glaucoma risk score' ascertained by questionnaire. The advisory panel recommended that further exploration of the feasibility of screening higher risk populations and detailed specification of the screening tests was required. CONCLUSIONS: With systematic use of expert opinions, a shortlist of potential screening interventions was identified. Views of users, service providers and cost-effectiveness modeling are now required to identify a feasible intervention to evaluate in a future glaucoma screening trial.

Performance of health workers in the management of seriously sick children at a Kenyan tertiary hospital: before and after a training intervention.

BACKGROUND: Implementation of WHO case management guidelines for serious common childhood illnesses remains a challenge in hospitals in low-income countries. The impact of locally adapted clinical practice guidelines (CPGs) on the quality-of-care of patients in tertiary hospitals has rarely been evaluated. METHODS AND FINDINGS: We conducted, in Kenyatta National Hospital, an uncontrolled before and after study with an attempt to explore intervention dose-effect relationships, as CPGs were disseminated and training was progressively implemented. The emergency triage, assessment and treatment plus admission care (ETAT+) training and locally adapted CPGs targeted common, serious childhood illnesses. We compared performance in the pre-intervention (2005) and post-intervention periods (2009) using quality indicators for three diseases: pneumonia, dehydration and severe malnutrition. The indicators spanned four domains in the continuum of care namely assessment, classification, treatment, and follow-up care in the initial 48 hours of admission. In the pre-intervention period patients' care was largely inconsistent with the guidelines, with nine of the 15 key indicators having performance of below 10%. The intervention produced a marked improvement in guideline adherence with an absolute effect size of over 20% observed in seven of the 15 key indicators; three of which had an effect size of over 50%. However, for all the five indicators that required sustained team effort performance continued to be poor, at less than 10%, in the post-intervention period. Data from the five-year period (2005-09) suggest some dose dependency though the adoption rate of the best-practices varied across diseases and over time. CONCLUSION: Active dissemination of locally adapted clinical guidelines for common serious childhood illnesses can achieve a significant impact on documented clinical practices, particularly for tasks that rely on competence of individual clinicians. However, more attention must be given to broader implementation strategies that also target institutional and organisational aspects of service delivery to further enhance quality-of-care.

Developing the clinical components of a complex intervention for a glaucoma screening trial: a mixed methods study.

BACKGROUND: Glaucoma is a leading cause of avoidable blindness worldwide. Open angle glaucoma is the most common type of glaucoma. No randomised controlled trials have been conducted evaluating the effectiveness of glaucoma screening for reducing sight loss. It is unclear what the most appropriate intervention to be evaluated in any glaucoma screening trial would be. The purpose of this study was to develop the clinical components of an intervention for evaluation in a glaucoma (open angle) screening trial that would be feasible and acceptable in a UK eye-care service. METHODS: A mixed-methods study, based on the Medical Research Council (MRC) framework for complex interventions, integrating qualitative (semi-structured interviews with 46 UK eye-care providers, policy makers and health service commissioners), and quantitative (economic modelling) methods. Interview data were synthesised and used to revise the screening interventions compared within an existing economic model. RESULTS: The qualitative data indicated broad based support for a glaucoma screening trial to take place in primary care, using ophthalmic trained technical assistants supported by optometry input. The precise location should be tailored to local circumstances. There was variability in opinion around the choice of screening test and target population. Integrating the interview findings with cost-effectiveness criteria reduced 189 potential components to a two test intervention including either optic nerve photography or screening mode perimetry (a measure of visual field sensitivity) with or without tonometry (a measure of intraocular pressure). It would be more cost-effective, and thus acceptable in a policy context, to target screening for open angle glaucoma to those at highest risk but for both practicality and equity arguments the optimal strategy was screening a general population cohort beginning at age forty. CONCLUSIONS: Interventions for screening for open angle glaucoma that would be feasible from a service delivery perspective were identified. Integration within an economic modelling framework explicitly highlighted the trade-off between cost-effectiveness, feasibility and equity. This study exemplifies the MRC recommendation to integrate qualitative and quantitative methods in developing complex interventions. The next step in the development pathway should encompass the views of service users.

Patients' engagement with "Sweet Talk" - a text messaging support system for young people with diabetes.

BACKGROUND: Guidelines for optimizing type 1 diabetes in young people advocate intensive insulin therapy coupled with personal support from the health care team. "Sweet Talk" is a novel intervention designed to support patients between clinic visits using text messages sent to a mobile phone. Scheduled messages are tailored to patient profiles and diabetes self-management goals, and generic messages include topical "newsletters" and anonymized tips from other participants. The system also allows patients to submit data and questions to the diabetes care team. OBJECTIVES: The aim was to explore how patients with type 1 diabetes interact with the Sweet Talk system in order to understand its utility to this user group. METHODS: Subjects were 64 young people with diabetes who were participating in the intervention arms of a randomized controlled trial. All text messages submitted to Sweet Talk during a 12-month period were recorded. Messaging patterns and content were analyzed using mixed quantitative and qualitative methods. RESULTS: Patients submitted 1180 messages during the observation period (mean 18.4, median 6). Messaging frequency ranged widely between participants (0-240) with a subset of 5 high users contributing 52% of the total. Patients' clinical and sociodemographic characteristics were not associated with total messaging frequency, although girls sent significantly more messages unrelated to diabetes than did boys (P = .002). The content of patients' messages fell into 8 main categories: blood glucose readings, diabetes questions, diabetes information, personal health administration, social messages, technical messages, message errors, and message responses. Unprompted submission of blood glucose values was the most frequent incoming message type (35% of total). Responses to requests for personal experiences and tips generated 40% of all the incoming messages, while topical news items also generated good responses. Patients also used the service to ask questions, submit information about their self-management, and order supplies. No patients nominated supporters to receive text messages about their self-management goals. Another option that was not used was the birthday reminder service. CONCLUSIONS: Automated, scheduled text messaging successfully engaged young people with diabetes. While the system was primarily designed to provide "push" support to patients, submission of clinical data and queries illustrates that it was seen as a trusted medium for communicating with care providers. Responses to the newsletters and submission of personal experiences and tips for circulation to other participants also illustrate the potential value of such interventions for establishing a sense of community. Although participants submitted relatively few messages, positive responses to the system suggest that most derived passive support from reading the messages. The Sweet Talk system could be readily adapted to suit other chronic disease models and age groups, and the results of this study may help to inform the design of future text message support interventions.

Representations of rituals and care in perinatal death in British midwifery textbooks 1937-2004.

OBJECTIVE: to assess the evolution of attitudes and practices relating to perinatal loss through an analysis of British midwifery textbooks. DESIGN: a literature review of midwifery textbooks, written or edited by midwives, published in the UK after 1902, and a critical analysis of textbooks to determine the ideological and professional standpoints presented to readers. FINDINGS: the rhetoric and ritual relating to perinatal loss as portrayed in British midwifery textbooks has changed, with the most dramatic changes taking place in the past 30 years. Evidence to support the changes is largely anecdotal, and little reference is made to research relating to perinatal death. The 'dirty' elements of perinatal death relating to the decay that takes place in the baby's body after death are not addressed. The critique of psychological theory relating to loss is absent, as are alternatives to the model proposed by Kübler Ross. Cultural aspects of loss and bereavement are rarely addressed. KEY CONCLUSIONS: the review of midwifery textbooks suggests that an ideological shift has taken place in relation to perinatal loss. The changing demographic trends, and the shift of birth and death from home to hospital, have altered the expectations and experiences of parents and professionals. Midwifery textbooks provide readers with a prescribed and formulaic approach to perinatal loss. IMPLICATIONS FOR PRACTICE: the absence of information relating to the appearance of the dead baby, together with the lack of clinical exposure, may mean that midwives are unable to provide parents with appropriate information. The lack of reference to an evidence base that may conflict with the ideology presented in the midwifery textbooks leaves readers with an incomplete understanding of the professional issues relating to perinatal loss.

Patient and health care professional views and experiences of computer agent-supported health care.

OBJECTIVES: To explore patient and health care professional (HCP) views towards the use of multi-agent computer systems in their GP practice. DESIGN: Qualitative analysis of in-depth interviews and analysis of transcriptions. SETTING: Urban health centre in Dundee, Scotland. PARTICIPANTS: Five representative healthcare professionals and 11 patients. MAIN OUTCOME MEASURES: Emergent themes from interviews revealed participants' attitudes and beliefs, which were coded and indexed. RESULTS: Patients and HCPs had similar beliefs, attitudes and views towards the implementation of multi-agent systems (MAS). Both felt modern communication methods were useful to supplement, not supplant, face-to-face consultations between doctors and patients. This was based on the immense trust these patients placed in their doctors in this practice, which extended to trust in their choice of communication technology and security. Rapid access to medical information increased patients' sense of shared partnership and self-efficacy. Patients and HCPs expressed respect for each other's time and were keen to embrace technology that made interactions more efficient, including for the altruistic benefit of others less technically competent. CONCLUSIONS: Patients and HCPs welcomed the introduction of agent technology to the delivery of health care. Widespread use will depend more on the trust patients place in their own GP than on technological issues.