Search

Background: There are an increasing number of interventions to improve hospital care for patients with dementia. Evidence for their impact on staff actions and patient outcomes is, however, limited and context dependent., Objective: To explain the factors that support hospital staff to provide dementia sensitive care and with what outcomes for patients with dementia., Design: A realist evaluation using a two-site case study approach., Setting: Two hospital trusts in the East of England. Site 1 had a ward for patients with dementia that would address their medical and mental health needs. Site 2 used a team of healthcare assistants, who had support from dementia specialist nurses, to work with patients with dementia across the hospital., Participants: Hospital staff who had a responsibility for inpatients with dementia (healthcare assistants, nurses, medical staff, allied healthcare professionals and support staff) (n = 36), patients with dementia (n = 28), and family carers of patients with dementia (n = 2)., Methods: A three stage realist evaluation: 1) building the programme theory of what works and when; 2) testing the programme theory through empirical data (80 h non-participant observation, 42 interviews, 28 patient medical notes, 27 neuropsychiatric inventory, and documentary review); 3) synthesis and verification of findings with key stakeholders., Findings: The programme theory comprised six interconnected context-mechanism-outcome configurations: 1) knowledge and authority to respond to an unmet need; 2) role relevant training and opportunities for reflection; 3) clinical experts and senior staff promoting practices that are patient-focused; 4) engaging with opportunities to spend time with patients; 5) risk management as an opportunity for person-centred care; 6) valuing dementia care as skilled work. Effective interactions reduced patient distress and supported patient orientation. Training and allocation of staff time were of themselves insufficient to ensure dementia care was prioritised and valued as skilled work. Staff concerns about the consequences of adverse incidents and work pressures on the ward, even with support, took precedence and influenced the quality of their interactions with patients with dementia. A key finding linked to staff retention and developing capacity in the workforce to provide expert dementia care was that despite extra training and organisational endorsement, nursing staff did not regard dementia care as skilled nursing work., Conclusions: There is increased awareness and organisational commitment to dementia-friendly healthcare in general hospitals. However, in addition to training and adapting the environment to the patient, further work is needed to make explicit the specialist skills required for effective dementia care., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Team-based care is an innovative approach to primary care in which groups of health care professionals work collaboratively to manage care for groups of patients. Safety-net organizations face specific barriers to implementing health care innovations. More research is needed that documents the dynamics that inform implementation and sustainment of innovative practices in the safety net., Methods: We conducted qualitative fieldwork, including purposeful observation and semi-structured and informal interviews, to explore the implementation of care teams in safety-net clinics in California. Field notes and transcripts were analyzed using an inductive approach to identify overarching themes across sites., Results: Salient themes across clinics suggest that 1) well-designed physical layouts that promote sustained patterns of structured and spontaneous communication and collaboration are critical to creating high-functioning teams; 2) implementation of team-based care relies on a relaxing of the traditional clinic hierarchy into an agile organizational structure that empowers all clinic staff-most notably medical assistants-by facilitating an ethos of collaborative decision-making, interdependence, and shared responsibility; and 3) resource constraints related to recruitment and retention of qualified staff are key barriers to implementation., Conclusions: Team-based care has the potential to improve patient outcomes, strengthen relationships and well-being among clinic staff, and expand staff roles to facilitate collective accomplishment of work goals. To successfully launch and sustain care teams in safety-net clinics, greater commitments to creating well-designed spaces and a re-envisioning of the training and compensation for medical assistants that reflects the valuable role these individuals can play appear to be necessary., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Maintenance of hematopoietic stem cell (HSC) quiescence is critical for self-renewal and differentiation into mature lineages. Therefore, the ability to reliably detect abnormal HSC cycling is essential for experiments that seek to investigate abnormalities of HSC function. The ability to reproducibly evaluate cell cycle status in a rare cell subset requires careful optimization of multiple parameters during cell preparation and sample processing. Here, we describe a method where data acquisition parameters and fluorochrome combination for long-term HSC staining have been specifically designed for concurrent use with DAPI and Ki-67 antibodies. © 2018 by John Wiley & Sons, Inc., (© 2018 John Wiley & Sons, Inc.)

Objectives: To measure changes in primary care physician (PCP) ordering rates for 4 global resource use measures before and after dissemination of physician feedback reports that provided peer-comparison resource use rates. We also explored whether physician practice characteristics (panel size, clinic size, and years of experience) were associated with resource use changes., Study Design: Pre-post implementation study measuring physician resource use in an integrated healthcare system (2011-2014)., Methods: Kaiser Permanente Washington PCPs (N = 210) were provided annual feedback reports showing their personal ordering rates compared with those of their peers. Monthly physician ordering was measured from November 2011 to September 2014 (including prereport and postreport periods). We examined 4 physician ordering rates (specialty referrals, high-end imaging, laboratory tests, and 30-day prescriptions) per 1000 patients, adjusted for patient age, gender, and clinical complexity., Results: After accounting for physician practice characteristics, monthly PCP ordering rates for high-end imaging significantly decreased by 0.8 images per 1000 patients (P <.01). In contrast, orders for laboratory tests and 30-day prescriptions significantly increased by 15.0 tests and 84.7 prescriptions per 1000 patients (both P <.01). We observed greater changes following feedback in physicians with fewer years of experience (≤10 years), who had 4.2 fewer specialty referrals (P = .01) and 101.3 more 30-day prescriptions (P <.01) compared with those with more experience (>20 years)., Conclusions: Physician feedback reports may be associated with changes in physician resource use, and physicians with fewer years of experience may be more responsive to feedback reports. Better understanding of factors associated with changes in resource use is necessary for future targeted development of physician interventions.

Background: Many individuals with chronic kidney disease (CKD) do not receive guideline-concordant care. We examined the impact of a team-based primary care CKD registry on clinical measures and processes of care among patients with CKD cared for in a public safety-net health care delivery system., Study Design: Pragmatic trial of a CKD registry versus a usual-care registry for 1 year., Setting & Participants: Primary care providers (PCPs) and their patients with CKD in a safety-net primary care setting in San Francisco., Intervention: The CKD registry identified at point of care all patients with CKD, those with blood pressure (BP)>140/90mmHg, those without angiotensin-converting enzyme (ACE) inhibitor/angiotensin receptor blocker (ARB) prescription, and those without albuminuria quantification in the past year. It also provided quarterly feedback pertinent to these metrics to promote "outreach" to patients with CKD. The usual-care registry provided point-of-care cancer screening and immunization data., Outcomes: Changes in systolic BP at 12 months (primary outcome), proportion of patients with BP control, prescription of ACE inhibitors/ARBs, quantification of albuminuria, severity of albuminuria, and estimated glomerular filtration rate., Results: The patient population (n=746) had a mean age of 56.7±12.1 (standard deviation) years, was 53% women, and was diverse (8% non-Hispanic white, 35.7% black, 24.5% Hispanic, and 24.4% Asian). Randomization to the CKD registry (30 PCPs, 285 patients) versus the usual-care registry (49 PCPs, 461 patients) was associated with 2-fold greater odds of ACE inhibitor/ARB prescription (adjusted OR, 2.25; 95% CI, 1.45-3.49) and albuminuria quantification (adjusted OR, 2.44; 95% CI, 1.38-4.29) during the 1-year study period. Randomization to the CKD registry was not associated with changes in systolic BP, proportion of patients with uncontrolled BP, or degree of albuminuria or estimated glomerular filtration rate., Limitations: Potential misclassification of CKD; missing baseline medication data; limited to study of a public safety-net health care system., Conclusions: A team-based safety-net primary care CKD registry did not improve BP parameters, but led to greater albuminuria quantification and more ACE inhibitor/ARB prescriptions after 1 year. Adoption of team-based CKD registries may represent an important step in translating evidence into practice for CKD management., (Copyright © 2018 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: care home residents have high healthcare needs not fully met by prevailing healthcare models. This study explored how healthcare configuration influences resource use., Methods: a realist evaluation using qualitative and quantitative data from case studies of three UK health and social care economies selected for differing patterns of healthcare delivery to care homes. Four homes per area (12 in total) were recruited. A total of 239 residents were followed for 12 months to record resource-use. Overall, 181 participants completed 116 interviews and 13 focus groups including residents, relatives, care home staff, community nurses, allied health professionals and General Practitioners., Results: context-mechanism-outcome configurations were identified explaining what supported effective working between healthcare services and care home staff: (i) investment in care home-specific work that legitimises and values work with care homes; (ii) relational working which over time builds trust between practitioners; (iii) care which 'wraps around' care homes; and (iv) access to specialist care for older people with dementia. Resource use was similar between sites despite differing approaches to healthcare. There was greater utilisation of GP resource where this was specifically commissioned but no difference in costs between sites., Conclusion: activities generating opportunities and an interest in healthcare and care home staff working together are integral to optimal healthcare provision in care homes. Outcomes are likely to be better where: focus and activities legitimise ongoing contact between healthcare staff and care homes at an institutional level; link with a wider system of healthcare; and provide access to dementia-specific expertise., (© The Author(s) 2018. Published by Oxford University Press on behalf of the British Geriatrics Society.)

Health policies encourage implementing quality measurement with performance targets. The 2010-2015 California Medicaid waiver mandated quality measurement and reporting. In 2013, California safety net hospitals participating in the waiver set a voluntary performance target (the 90th percentile for Medicare preferred provider organization plans) for mammography screening and cholesterol control in diabetes. They did not reach the target, and the difference-in-differences analysis suggested that there was no difference for mammography ( P = .39) and low-density lipoprotein control ( P = .11) performance compared to measures for which no statewide quality improvement initiative existed. California's Medicaid waiver was associated with improved performance on a number of metrics, but this performance was not attributable to target setting on specific health conditions. Performance may have improved because of secular trends or systems improvements related to waiver funding. Relying on condition-specific targets to measure performance may underestimate improvements and disadvantage certain health systems. Achieving ambitious targets likely requires sustained fiscal, management, and workforce investments.

Future precipitation changes in a warming climate depend regionally upon the response of natural climate modes to anthropogenic forcing. North Pacific hydroclimate is dominated by the Aleutian Low, a semi-permanent wintertime feature characterized by frequent low-pressure conditions that is influenced by tropical Pacific Ocean temperatures through the Pacific-North American (PNA) teleconnection pattern. Instrumental records show a recent increase in coastal Alaskan precipitation and Aleutian Low intensification, but are of insufficient length to accurately assess low frequency trends and forcing mechanisms. Here we present a 1200-year seasonally- to annually-resolved ice core record of snow accumulation from Mt. Hunter in the Alaska Range developed using annual layer counting and four ice-flow thinning models. Under a wide range of glacier flow conditions and layer counting uncertainty, our record shows a doubling of precipitation since ~1840 CE, with recent values exceeding the variability observed over the past millennium. The precipitation increase is nearly synchronous with the warming of western tropical Pacific and Indian Ocean sea surface temperatures. While regional 20 th Century warming may account for a portion of the observed precipitation increase on Mt. Hunter, the magnitude and seasonality of the precipitation change indicate a long-term strengthening of the Aleutian Low.

Family history is essential when screening for hereditary cancer syndromes. This article explores if a detailed genetic family history questionnaire is more effective in identifying at-risk individuals for Lynch syndrome than a basic family health questionnaire.

Purpose: To characterize features associated with de novo mutations affecting SATB2 function in individuals ascertained on the basis of intellectual disability., Methods: Twenty previously unreported individuals with 19 different SATB2 mutations (11 loss-of-function and 8 missense variants) were studied. Fibroblasts were used to measure mutant protein production. Subcellular localization and mobility of wild-type and mutant SATB2 were assessed using fluorescently tagged protein., Results: Recurrent clinical features included neurodevelopmental impairment (19/19), absent/near absent speech (16/19), normal somatic growth (17/19), cleft palate (9/19), drooling (12/19), and dental anomalies (8/19). Six of eight missense variants clustered in the first CUT domain. Sibling recurrence due to gonadal mosaicism was seen in one family. A nonsense mutation in the last exon resulted in production of a truncated protein retaining all three DNA-binding domains. SATB2 nuclear mobility was mutation-dependent; p.Arg389Cys in CUT1 increased mobility and both p.Gly515Ser in CUT2 and p.Gln566Lys between CUT2 and HOX reduced mobility. The clinical features in individuals with missense variants were indistinguishable from those with loss of function., Conclusion: SATB2 haploinsufficiency is a common cause of syndromic intellectual disability. When mutant SATB2 protein is produced, the protein appears functionally inactive with a disrupted pattern of chromatin or matrix association.Genet Med advance online publication 02 February 2017.

Objectives: To identify features of programmes and approaches to make healthcare delivery in secondary healthcare settings more dementia-friendly, providing a context-relevant understanding of how interventions achieve outcomes for people living with dementia., Design: A realist review conducted in three phases: (1) stakeholder interviews and scoping of the literature to develop an initial programme theory for providing effective dementia care; (2) structured retrieval and extraction of evidence; and (3) analysis and synthesis to build and refine the programme theory., Data Sources: PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Library, NHS Evidence, Scopus and grey literature., Eligibility Criteria: Studies reporting interventions and approaches to make hospital environments more dementia-friendly. Studies not reporting patient outcomes or contributing to the programme theory were excluded., Results: Phase 1 combined findings from 15 stakeholder interviews and 22 publications to develop candidate programme theories. Phases 2 and 3 identified and synthesised evidence from 28 publications. Prominent context-mechanism-outcome configurations were identified to explain what supported dementia-friendly healthcare in acute settings. Staff capacity to understand the behaviours of people living with dementia as communication of an unmet need, combined with a recognition and valuing of their role in their care, prompted changes to care practices. Endorsement from senior management gave staff confidence and permission to adapt working practices to provide good dementia care. Key contextual factors were the availability of staff and an alignment of ward priorities to value person-centred care approaches. A preoccupation with risk generated responses that werelikely to restrict patient choice and increase their distress., Conclusions: This review suggests that strategies such as dementia awareness training alone will not improve dementia care or outcomes for patients with dementia. Instead, how staff are supported to implement learning and resources by senior team members with dementia expertise is a key component for improving care practices and patient outcomes., Trial Registration Number: CRD42015017562., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

The next phase of health-care reform will accelerate the formation of integrated delivery systems and the creation of value and savings through population health management. Accomplishing this goal requires 3 key factors, including (1) enabling groups of physicians and hospitals to legally work together to cover a broad geographic area, (2) the formation of integrated delivery systems that cover the low to high-acuity and post-acute care spectrums, and (3) identifying mechanisms through which a subspecialty can impact the health of a population of patients.At first glance, it would be easy to assume that this is largely a primary care initiative and that orthopaedic surgeons cannot influence population health since they often just repair things after they have broken or worn out. This symposium will challenge that assumption and demonstrate the potential for orthopaedic surgeons to play a major role in population health management. Some of the mechanisms include implementing shared decision-making for elective procedures, reducing premature/unnecessary imaging and subspecialty referrals, improving bone health (osteoporosis prevention and fall risk assessment), and developing payment methodologies to reward population-based, rather than individual-based, positive musculoskeletal outcomes.

Background: With population ageing, research is needed into new low-cost, scalable methods of effective promotion of health and wellbeing for older people. We aimed to assess feasibility, reach and costs of implementing a new tailored computer-aided health and social risk appraisal system in primary care., Methods: Design: Feasibility study., Setting: Five General Practices in London (Ealing) and Hertfordshire, United Kingdom (UK) Participants: Random sample of patients aged 65 + years., Intervention: The Multi-dimensional Risk Appraisal for Older people (MRA-O) system includes: 1) Postal questionnaire including health, lifestyle, social and environmental domains; 2) Software system generating a personalised feedback report with advice on health and wellbeing; 3) Follow-up of people with new concerning or complex needs by GPs or practice nurses., Evaluation: Feasibility of implementation; participant wellbeing, functional ability and quality of life; social needs, health risks, potential lifestyle changes; and costs of implementation., Results: Response rates to initial postal invitations were low (526/1550, 34%). Of these, 454/526 (86%) completed MRA-O assessments. Compared to local UK Census data on older people, participants were younger, more were owner-occupiers and fewer were from ethnic minority groups than expected. A range of problems was identified by participants, including pain in last week (269/438, 61.4%), low physical activity (173/453, 38.2%), sedentary lifestyle (174/447, 38.3%), falls (117/439, 26.7%), incontinence (111/441 25.2%), impaired vision 116/451 (25.7%), impaired hearing (145/431, 33.6%), depressed mood (71/451, 15.7%), impaired memory (44/444 9.9%), social isolation (46/449, 10.2%) and loneliness (31/442, 7.0%). Self-rated health was good/excellent in 312/437 (71.4%), and quality of life and well-being were slightly above age-specific population norms. Implementation costs were low. Practices reviewed medical records of 143/454 (31.5%) of participants as a consequence of their responses, and actively followed up 110/454 (24.2%) of their patients., Conclusions: A computer-aided risk appraisal system was feasible for General Practices to implement, yields useful information about health and social problems, and identifies individual needs. Participation rates were however low, particularly for the oldest old, the poorest, and ethnic minority groups, and this type of intervention may increase inequalities in access. Widespread implementation of this approach would require work to address potential inequalities.

Objectives: There has been significant research on provider attribution for quality and cost. Low-value care is an area of heightened focus, with little of the focus being on measurement; a key methodological decision is how to attribute delivered services and procedures. We illustrate the difference in relative and absolute physician- and panel-attributed services and procedures using overuse in cervical cancer screening., Study Design: A retrospective, cross-sectional study in an integrated health care system., Methods: We used 2013 physician-level data from Group Health Cooperative to calculate two utilization attributions: (1) panel attribution with the procedure assigned to the physician's predetermined panel, regardless of who performed the procedure; and (2) physician attribution with the procedure assigned to the performing physician. We calculated the percentage of low-value cervical cancer screening tests and ranked physicians within the clinic using the two utilization attribution methods., Results: The percentage of low-value cervical cancer screening varied substantially between physician and panel attributions. Across the whole delivery system, median panel- and physician-attributed percentages were 15 percent and 10 percent, respectively. Among sampled clinics, panel-attributed percentages ranged between 10 percent and 17 percent, and physician-attributed percentages ranged between 9 percent and 13 percent. Within a clinic, median panel-attributed screening percentage was 17 percent (range 0 percent-27 percent) and physician-attributed percentage was 11 percent (range 0 percent-24 percent); physician rank varied by attribution method., Conclusions: The attribution method is an important methodological decision when developing low-value care measures since measures may ultimately have an impact on national benchmarking and quality scores. Cross-organizational dialogue and transparency in low-value care measurement will become increasingly important for all stakeholders.

Context: Perceptions about low-value care (eg, medical tests and procedures that may be unnecessary and/or harmful) among clinicians with capitated salaries are unknown., Objective: Explore clinicians' perceived use of and responsibility for reducing low-value care by focusing on barriers to use, awareness of the Choosing Wisely campaign, and response to reports of peer-comparison resource use and practice patterns., Methods: Electronic, cross-sectional survey, distributed in 2013, to 304 salaried primary care physicians and physician assistants at Group Health Cooperative., Main Outcome Measures: Attitudes, awareness, and barriers of low-value care strategies and initiatives., Results: A total of 189 clinicians responded (62% response rate). More than 90% believe cost is important to various stakeholders and believe it is fair to ask clinicians to be cost-conscious. Most found peer-comparison resource-use reports useful for understanding practice patterns and prompting peer discussions. Two-thirds of clinicians were aware of the Choosing Wisely campaign; among them, 97% considered it a legitimate information source. Although 88% reported being comfortable discussing low-value care with patients, 80% reported they would order tests or procedures when a patient insisted. As key barriers in reducing low-value care, clinicians identified time constraints (45%), overcoming patient preferences/values (44%), community standards (43%), fear of patients' dissatisfaction (41%), patients' knowledge about the harms of low-value care (38%), and availability of tools to support shared decision making (37%)., Conclusions: Salaried clinicians are aware of rising health care costs and want to be stewards of limited health care resources. Evidence-based initiatives such as the Choosing Wisely campaign may help motivate clinicians to be conscientious stewards of limited health care resources.

Background: Care home residents in England have variable access to health care services. There is currently no coherent policy or consensus about the best arrangements to meet these needs. The purpose of this review was to explore the evidence for how different service delivery models for care home residents support and/or improve wellbeing and health-related outcomes in older people living and dying in care homes., Methods: We conceptualised models of health care provision to care homes as complex interventions. We used a realist review approach to develop a preliminary understanding of what supported good health care provision to care homes. We completed a scoping of the literature and interviewed National Health Service and Local Authority commissioners, providers of services to care homes, representatives from the Regulator, care home managers, residents and their families. We used these data to develop theoretical propositions to be tested in the literature to explain why an intervention may be effective in some situations and not others. We searched electronic databases and related grey literature. Finally the findings were reviewed with an external advisory group., Results: Strategies that support and sustain relational working between care home staff and visiting health care professionals explained the observed differences in how health care interventions were accepted and embedded into care home practice. Actions that encouraged visiting health care professionals and care home staff jointly to identify, plan and implement care home appropriate protocols for care, when supported by ongoing facilitation from visiting clinicians, were important. Contextual factors such as financial incentives or sanctions, agreed protocols, clinical expertise and structured approaches to assessment and care planning could support relational working to occur, but of themselves appeared insufficient to achieve change., Conclusion: How relational working is structured between health and care home staff is key to whether health service interventions achieve health related outcomes for residents and their respective organisations. The belief that either paying clinicians to do more in care homes and/or investing in training of care home staff is sufficient for better outcomes was not supported.

Gillespie syndrome (GS) is characterized by bilateral iris hypoplasia, congenital hypotonia, non-progressive ataxia, and progressive cerebellar atrophy. Trio-based exome sequencing identified de novo mutations in ITPR1 in three unrelated individuals with GS recruited to the Deciphering Developmental Disorders study. Whole-exome or targeted sequence analysis identified plausible disease-causing ITPR1 mutations in 10/10 additional GS-affected individuals. These ultra-rare protein-altering variants affected only three residues in ITPR1: Glu2094 missense (one de novo, one co-segregating), Gly2539 missense (five de novo, one inheritance uncertain), and Lys2596 in-frame deletion (four de novo). No clinical or radiological differences were evident between individuals with different mutations. ITPR1 encodes an inositol 1,4,5-triphosphate-responsive calcium channel. The homo-tetrameric structure has been solved by cryoelectron microscopy. Using estimations of the degree of structural change induced by known recessive- and dominant-negative mutations in other disease-associated multimeric channels, we developed a generalizable computational approach to indicate the likely mutational mechanism. This analysis supports a dominant-negative mechanism for GS variants in ITPR1. In GS-derived lymphoblastoid cell lines (LCLs), the proportion of ITPR1-positive cells using immunofluorescence was significantly higher in mutant than control LCLs, consistent with an abnormality of nuclear calcium signaling feedback control. Super-resolution imaging supports the existence of an ITPR1-lined nucleoplasmic reticulum. Mice with Itpr1 heterozygous null mutations showed no major iris defects. Purkinje cells of the cerebellum appear to be the most sensitive to impaired ITPR1 function in humans. Iris hypoplasia is likely to result from either complete loss of ITPR1 activity or structure-specific disruption of multimeric interactions., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The ABC End of Life Education Programme trained approximately 3000 care home staff in End of Life (EoL) care. An evaluation that compared this programme with the Gold Standards Framework found that it achieved equivalent outcomes at a lower cost with higher levels of staff satisfaction. To consolidate this learning, a facilitated peer education model that used the ABC materials was piloted. The goal was to create a critical mass of trained staff, mitigate the impact of staff turnover and embed EoL care training within the organisations. The aim of the study was to evaluate the feasibility of using a train the trainer (TTT) model to support EoL care in care homes., Methods: A mixed method design involved 18 care homes with and without on-site nursing across the East of England. Data collection included a review of care home residents' characteristics and service use (n = 274), decedents' notes n = 150), staff interviews (n = 49), focus groups (n = 3), audio diaries (n = 28) and observations of workshops (n = 3)., Results: Seventeen care homes participated. At the end of the TTT programme 28 trainers and 114 learners (56% of the targeted number of learners) had been trained (median per home 6, range 0-13). Three care homes achieved or exceeded the set target of training 12 learners. Trainers ranged from senior care staff to support workers and administrative staff. Results showed a positive association between care home stability, in terms of leadership and staff turnover, and uptake of the programme. Care home ownership, type of care home, size of care home, previous training in EoL care and resident characteristics were not associated with programme completion. Working with facilitators was important to trainers, but insufficient to compensate for organisational turbulence. Variability of uptake was also linked to management support, programme fit with the trainers' roles and responsibilities and their opportunities to work with staff on a daily basis., Conclusion: When there is organisational stability, peer to peer approaches to skills training in end of life care can, with expert facilitation, cascade and sustain learning in care homes.

Background: Improving health-care outcomes for people living with dementia when they are admitted to hospital is a policy priority. Dementia friendly interventions in health care promote inclusion of patients and carers in decision-making and adapt practices and environments to be appropriate to the needs of people with cognitive impairment. While there has been a wealth of activity, the number of studies evaluating interventions is limited, and the majority focuses on reporting staff and organisational outcomes. By focusing on patient and carer outcomes, this review will aim to develop an explanatory account of how and in what circumstances dementia friendly environments in health care work for people living with dementia and with what outcomes., Method/design: Realist review is a theory-driven method which seeks to produce explanatory accounts of why interventions work and specifically, what combination of components are most effective in producing particular outcomes. Stakeholder interviews, a review of the literature, and an expert steering group workshop will be used to explore the assumptions behind interventions that are designed to enhance health care for people living with dementia to understand the underlying programme theories. The review will focus on studies that report patient and carer outcomes, including involvement in decision-making, length of stay and referral to long-term care, adverse incidents (e.g. patient distress, delirium falls, nutrition and hydration and infection), antipsychotic medication prescribing, evidence of patient-centred care and patient and carer satisfaction., Discussion: The review will provide an explanatory model about how dementia friendly interventions in hospital settings improve outcomes for people living with dementia and their family carers and in what circumstances for future testing and evaluation of future dementia friendly initiatives., Systematic Review Registration: PROSPERO CRD42015017562.

Objective: Patient-provider communication about complementary health approaches can support diabetes self-management by minimizing risk and optimizing care. We sought to identify sociodemographic and communication factors associated with disclosure of complementary health approaches to providers by low-income patients with diabetes., Methods: We used data from San Francisco Health Plan's SMARTSteps Program, a trial of diabetes self-management support for low-income patients (n=278) through multilingual automated telephone support. Interviews collected use and disclosure of complementary health approaches in the prior month, patient-physician language concordance, and quality of communication., Results: Among racially, linguistically diverse participants, half (47.8%) reported using complementary health practices (n=133), of whom 55.3% disclosed use to providers. Age, sex, race/ethnicity, nativity, education, income, and health literacy were not associated with disclosure. In adjusted analyses, disclosure was associated with language concordance (AOR=2.21, 95% CI: 1.05, 4.67), physicians' interpersonal communication scores (AOR=1.50, 95% CI: 1.03, 2.19), shared decision making (AOR=1.74, 95% CI: 1.33, 2.29), and explanatory-type communication (AOR=1.46, 95% CI: 1.03, 2.09)., Conclusion: Safety net patients with diabetes commonly use complementary health approaches and disclose to providers with higher patient-rated quality of communication., Practice Implications: Patient-provider language concordance and patient-centered communication can facilitate disclosure of complementary health approaches., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Chronic kidney disease (CKD) is common and is associated with excess mortality and morbidity. Better management could slow progression of disease, prevent metabolic complications, and reduce cardiovascular outcomes. Low patient awareness of CKD and ineffective patient-provider communication can impede such efforts. We developed provider and patient-directed interventions that harness health information technology to enhance provider recognition of CKD and delivery of guideline concordant care and augment patient understanding and engagement in CKD care., Methods/design: We report the design and protocol of the Kidney Awareness Registry and Education (KARE) Study, a 2x2 factorial randomized controlled trial that examines the impact of a multi-level intervention on health outcomes among low-income English, Spanish and Cantonese-speaking patients with CKD in a safety net system. The intervention includes: (1) implementation of a primary care electronic CKD registry that notifies practice teams of patients' CKD status and employs a patient profile and quarterly feedback to encourage provision of guideline-concordant care at point-of-care and via outreach; and (2) a language-concordant, culturally-sensitive self-management support program that consists of automated telephone modules, provision of low-literacy written patient-educational materials and telephone health coaching. The primary outcomes of the trial are changes in systolic blood pressure (BP) and the proportion of patients with BP control (≤ 140/90 mmHg) after one year. Secondary outcomes include patient understanding of CKD, participation in healthy behaviors, and practice team delivery of guideline-concordant CKD care., Discussion: Results from the KARE study will provide data on the feasibility, effectiveness, and acceptability of technology-based interventions that support primary care efforts at improving health outcomes among vulnerable patients with CKD., Trial Registration: ClinicalTrials.gov, number: NCT01530958.

Background: With the expansion of Medicaid and low-cost health insurance plans among diverse patient populations, objective measures of medication adherence using pharmacy claims could advance clinical care and translational research for safety net care. However, safety net patients may experience fluctuating prescription drug coverage, affecting the performance of adherence measures., Objective: To evaluate the performance of continuous medication gap (CMG) for diverse, low-income managed care members with diabetes., Methods: We conducted this cross-sectional analysis using administrative and clinical data for 680 members eligible for a self-management support trial at a nonprofit, government-sponsored managed care plan. We applied CMG methodology to cardiometabolic medication claims for English- , Cantonese- , or Spanish-speaking members with diabetes. We examined inclusiveness (the proportion with calculable CMG) and selectivity (sociodemographic and medical differences from members without CMG). For validity, we examined unadjusted associations of suboptimal adherence (CMG >  20%) with suboptimal cardiometabolic control., Results: 429 members (63%) had calculable CMG. Compared with members without CMG, members with CMG were younger, more likely employed, and had poorer glycemic control but had better blood pressure and lipid control. Suboptimal adherence occurred more frequently among members with poor cardiometabolic control than among members with optimal control (28% vs. 12%, P = 0.02)., Conclusions: CMG demonstrated acceptable inclusiveness and validity in a diverse, low-income safety net population, comparable with its performance in studies among other insured populations. CMG may provide a useful tool to measure adherence among increasingly diverse Medicaid populations, complemented by other strategies to reach those not captured by CMG.

Adaptive cellular immunity requires accurate self- vs. nonself-discrimination to protect against infections and tumorous transformations while at the same time excluding autoimmunity. This vital capability is programmed in the thymus through selection of αβT-cell receptors (αβTCRs) recognizing peptides bound to MHC molecules (pMHC). Here, we show that the pre-TCR (preTCR), a pTα-β heterodimer appearing before αβTCR expression, directs a previously unappreciated initial phase of repertoire selection. Contrasting with the ligand-independent model of preTCR function, we reveal through NMR and bioforce-probe analyses that the β-subunit binds pMHC using Vβ complementarity-determining regions as well as an exposed hydrophobic Vβ patch characteristic of the preTCR. Force-regulated single bonds akin to those of αβTCRs but with more promiscuous ligand specificity trigger calcium flux. Thus, thymic development involves sequential β- and then, αβ-repertoire tuning, whereby preTCR interactions with self pMHC modulate early thymocyte expansion, with implications for β-selection, immunodominant peptide recognition, and germ line-encoded MHC interaction.

Objectives: To examine the relationships among implementing decision aids (DAs) for benign prostatic hyperplasia (BPH) and prostate cancer (PRCA), and treatment rates and costs., Study Design: A pre-post observational evaluation of a quality improvement initiative in a healthcare system in Washington state., Methods: Men with BPH seen in urology clinics and all men diagnosed with localized PRCA were identified for an intervention period, in which urologists were instructed to order a DA for every patient with those conditions, and a historical control period. Outcomes were 6-month rates of surgery for BPH, any active treatment (hormone therapy, radiation, or surgery) for PRCA, and total healthcare costs. Results During the intervention, DAs were delivered to 22% of men with recent BPH drug treatment, 24% of men with untreated BPH, and 56% of men with PRCA. DA implementation was associated with a 32% lower rate of surgery among men with treated BPH (rate ratio [RR], 0.68; 95% CI, 0.49-0.94) and a nonsignificant 22% lower rate of surgery among men with previously untreated BPH (RR, 0.78; 95% CI, 0.50-1.22). For PRCA, DA implementation was associated with a 27% lower rate of active treatment (RR, 0.73; 95% CI, 0.57-0.93). We found no significant associations between DA implementation and costs of care for either condition., Conclusions: Implementing patient DAs was associated with lower rates of elective surgery for previously treated BPH and active treatment for localized PRCA; however, implementation of these DAs was not associated with lower costs of care.

Many women develop postpartum mental health symptoms, ranging from the maternity blues to clinically diagnosed postpartum depression (PPD). Substantial literature supports an association between depression and type 2 diabetes, but there is limited literature regarding to what extent this relationship pertains to gestational diabetes (GDM) and postpartum depression. Review of the literature regarding GDM and PPD with a particular focus on describing the prevalence of PPD among women who may be at increased risk for GDM, including low-income and ethnic minority groups, was performed. Literature searches were conducted across four databases for studies reporting postpartum mental health outcomes (including postpartum depression, behavioral symptoms, mental disorders, mood, anxiety, quality of life) following a diagnosis of GDM. Studies including subgroups of women with GDM were included if postpartum mental health outcomes were reported. Of the 245 abstracts identified, ten studies were included in the final review. Findings suggest that PPD was high among low-income, ethnic minority women. Additional research is required to understand the complex relationship between GDM and PPD among low-income women, with the ultimate goal of implementing tailored interventions to address their medical and psychiatric needs.

Background: Older people living in care homes often have limited life expectancy. Practitioners and policymakers are increasingly questioning the appropriateness of many acute hospital admissions and the quality of end-of-life care provided in care homes., Aim: To describe care home residents' trajectories to death and care provision in their final weeks of life., Design and Setting: Prospective study of residents in six residential care homes in three sociodemographically varied English localities: Hertfordshire, Essex, and Cambridgeshire., Method: Case note reviews and interviews with residents, care home staff, and healthcare professionals., Results: Twenty-three out of 121 recruited residents died during the study period. Four trajectories to death were identified: 'anticipated dying' with an identifiable end-of-life care period and death in the care home (n = 9); 'unexpected dying' with death in the care home that was not anticipated and often sudden (n = 3); 'uncertain dying' with a period of diagnostic uncertainty or difficult symptom management leading to hospital admission and inpatient death (n = 7); and 'unpredictable dying' with an unexpected event leading to hospital admission and inpatient death (n = 4). End-of-life care tools were rarely used. Most residents who had had one or more acute hospital admission were still alive at the end of the study., Conclusion: For some care home residents there was an identifiable period when they were approaching the end-of-life and planned care was put in place. For others, death came unexpectedly or during a period of considerable uncertainty, with care largely unplanned and reactive to events., (© British Journal of General Practice 2014.)

Flavivirus NS3 and NS5 are required in viral replication and 5'-capping. NS3 has NS2B-dependent protease, RNA helicase, and 5'-RNA triphosphatase activities. NS5 has 5'-RNA methyltransferase (MT)/guanylyltransferase (GT) activities within the N-terminal 270 amino acids and the RNA-dependent RNA polymerase (POL) activity within amino acids 271-900. A chimeric NS5 containing the D4MT/D4GT and the D2POL domains in the context of wild-type (WT) D2 RNA was constructed. RNAs synthesized in vitro were transfected into baby hamster kidney cells. The viral replication was analyzed by an indirect immunofluorescence assay to monitor NS1 expression and by quantitative real-time PCR. WT D2 RNA-transfected cells were NS1- positive by day 5, whereas the chimeric RNA-transfected cells became NS1-positive ∼30 days post-transfection in three independent experiments. Sequence analysis covering the entire genome revealed the appearance of a single K74I mutation within the D4MT domain ∼16 days post-transfection in two experiments. In the third, D290N mutation in the conserved NS3 Walker B motif appeared ≥16 days post-transfection. A time course study of serial passages revealed that the 30-day supernatant had gradually evolved to gain replication fitness. Trans-complementation by co-expression of WT D2 NS5 accelerated viral replication of chimeric RNA without changing the K74I mutation. However, the MT and POL activities of NS5 WT D2 and the chimeric NS5 proteins with or without the K74I mutation are similar. Taken together, our results suggest that evolution of the functional interactions involving the chimeric NS5 protein encoded by the viral genome species is essential for gain of viral replication fitness., (© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.)

Physician use of secure e-mail with patients is anticipated to increase under Stage 2 Meaningful Use requirements, but little is known about how physicians can successfully incorporate it into daily work. We interviewed 27 "super user" physicians at Kaiser Permanente and Group Health who were identified by leaders as being technologically, operationally, and clinically adept and as having high levels of secure e-mail use with patients. They highly valued the use of secure e-mail with patients, despite concerns about a lack of adequate time to respond, and provided tips for using it successfully. They identified benefits that included better care and improved relationships with their patients.

The aim of the study was to describe the expectations and experiences of end-of-life care of older people resident in care homes, and how care home staff and the healthcare practitioners who visited the care home interpreted their role. A mixed-method design was used. The everyday experience of 121 residents from six care homes in the East of England were tracked; 63 residents, 30 care home staff with assorted roles and 19 National Health Service staff from different disciplines were interviewed. The review of care home notes demonstrated that residents had a wide range of healthcare problems. Length of time in the care homes, functional ability or episodes of ill-health were not necessarily meaningful indicators to staff that a resident was about to die. General Practitioner and district nursing services provided a frequent but episodic service to individual residents. There were two recurring themes that affected how staff engaged with the process of advance care planning with residents; 'talking about dying' and 'integrating living and dying'. All participants stated that they were committed to providing end-of-life care and supporting residents to die in the care home, if wanted. However, the process was complicated by an ongoing lack of clarity about roles and responsibilities in providing end-of-life care, doubts from care home and primary healthcare staff about their capacity to work together when residents' trajectories to death were unclear. The findings suggest that to support this population, there is a need for a pattern of working between health and care staff that can encourage review and discussion between multiple participants over sustained periods of time., (© 2013 John Wiley & Sons Ltd.)

The nursing faculty shortage is directly related to the ongoing shortage of nurses. As a result of many nursing faculty retiring, the discipline of nursing is losing its most experienced educators. The need is great for programs that will increase access and prepare nurse educators. Doctorate degrees for nurses have evolved in myriad ways. Discussions over the nature of doctoral education for the preparation of nurse educators are at the forefront of debates in nursing education. In response to National League for Nursing (2007; Core competencies of nurse educators, http://www.nln.org/profdev/corecompletter.htm) and Institute of Medicine (2010; The future of nursing: Leading change, advancing health. Washington, DC: National Academies Press, http://thefutureofnursing.org/IOM-Report) calls to increase the number of nursing faculty, the colleges of nursing and education at a major university have combined to establish a collaborative doctoral program. This article describes the historical evolution of the nursing doctorate degrees and the development and implementation of the EdD in Instructional Leadership for Nurse Educators.

Background: Interactive health information technology (HIT) can support the complex self-management tasks for diabetes. However, less is known about between-visit interactions and patient safety among chronic illness patients treated in the outpatient setting., Methods: We classified 13 categories for safety events and potential safety events within a larger trial evaluating a multilingual automated telephone self-management support system for diabetes using interactive voice response. Participants could trigger safety concerns by reporting hyperglycemia or hypoglycemia, inability to obtain medications, medication nonadherence and side effects, and needing appointments and/or supplies. We then examined these triggers across patient demographic and health characteristics to determine which patients were most likely to experience safety events., Results: Overall, there were 360 safety triggers that occurred among 155 participants, which represented 53% of individuals and 7.6% of all automated calls over the 27-week intervention. The most common triggers were for pain or medication side effects (22%) and not checking blood sugars (13%). In adjusted models, race/ethnicity and language were related to safety triggers; Spanish-speaking participants were significantly (p = .02) more likely than English-speaking participants to experience a safety trigger, and black participants were marginally more likely (p = .09) than white participants to experience a safety trigger., Conclusion: About half of patients enrolled in a self-management technology intervention triggered at least one potential safety event over the course of the trial, and this was more frequent among some patients. Systems implementing HIT strategies to improve self-care and remote monitoring should consider specific program design elements to address these potential safety events., (© 2013 Diabetes Technology Society.)

The expression and function of several multidrug transporters (including ABCB1 and ABCG2) have been studied in human cancer cells and in mouse and human adult stem cells. However, the expression of ABCG2 in human embryonic stem cells (hESCs) remains unclear. Limited and contradictory results in the literature from two research groups have raised questions regarding its expression and function. In this study, we used quantitative real-time PCR, Northern blots, whole genome RNA sequencing, Western blots, and immunofluorescence microscopy to study ABCG2 expression in hESCs. We found that full-length ABCG2 mRNA transcripts are expressed in undifferentiated hESC lines. However, ABCG2 protein was undetectable even under embryoid body differentiation or cytotoxic drug induction. Moreover, surface ABCG2 protein was coexpressed with the differentiation marker stage-specific embryonic antigen-1 of hESCs, following constant BMP-4 signaling at days 4 and 6. This expression was tightly correlated with the downregulation of two microRNAs (miRNAs) (i.e., hsa-miR-519c and hsa-miR-520h). Transfection of miRNA mimics and inhibitors of these two miRNAs confirmed their direct involvement in the regulation ABCG2 translation. Our findings clarify the controversy regarding the expression of the ABCG2 gene and also provide new insights into translational control of the expression of membrane transporter mRNAs by miRNAs in hESCs., (Copyright © 2012 AlphaMed Press.)

The role of IκB kinase (IKK)-induced proteolysis of NF-κB1 p105 in innate immune signaling was investigated using macrophages from Nfkb1(SSAA/SSAA) mice, in which the IKK target serines on p105 are mutated to alanines. We found that the IKK/p105 signaling pathway was essential for TPL-2 kinase activation of extracellular signal-regulated kinase (ERK) mitogen-activate protein (MAP) kinase and modulated the activation of NF-κB. The Nfkb1(SSAA) mutation prevented the agonist-induced release of TPL-2 from its inhibitor p105, which blocked activation of ERK by lipopolysaccharide (LPS), tumor necrosis factor (TNF), CpG, tripalmitoyl-Cys-Ser-Lys (Pam(3)CSK), poly(I · C), flagellin, and R848. The Nfkb1(SSAA) mutation also prevented LPS-induced processing of p105 to p50 and reduced p50 levels, in addition to decreasing the nuclear translocation of RelA and cRel. Reduced p50 in Nfkb1(SSAA/SSAA) macrophages significantly decreased LPS induction of the IκBζ-regulated Il6 and Csf2 genes. LPS upregulation of Il12a and Il12b mRNAs was also impaired although specific blockade of TPL-2 signaling increased expression of these genes at late time points. Activation of TPL-2/ERK signaling by IKK-induced p105 proteolysis, therefore, induced a negative feedback loop to downregulate NF-κB-dependent expression of the proinflammatory cytokine interleukin-12 (IL-12). Unexpectedly, TPL-2 promoted soluble TNF production independently of IKK-induced p105 phosphorylation and its ability to activate ERK, which has important implications for the development of anti-inflammatory drugs targeting TPL-2.

Decision aids are evidence-based sources of health information that can help patients make informed treatment decisions. However, little is known about how decision aids affect health care use when they are implemented outside of randomized controlled clinical trials. We conducted an observational study to examine the associations between introducing decision aids for hip and knee osteoarthritis and rates of joint replacement surgery and costs in a large health system in Washington State. Consistent with prior randomized trials, our introduction of decision aids was associated with 26 percent fewer hip replacement surgeries, 38 percent fewer knee replacements, and 12-21 percent lower costs over six months. These findings support the concept that patient decision aids for some health conditions, for which treatment decisions are highly sensitive to both patients' and physicians' preferences, may reduce rates of elective surgery and lower costs.

Background: Primary care providers (PCPs) in safety net settings face barriers to optimizing care for patients with diabetes. We conducted this study to assess PCPs' perspectives on the effectiveness of two language-concordant diabetes self-management support programs., Methods: One year postintervention, we surveyed PCPs whose patients with diabetes participated in a three-arm multiclinic randomized controlled trial comparing usual care (UC), weekly automated telephone self-management (ATSM) support with nurse care management, and monthly group medical visits (GMVs). We compared PCP perspectives on patient activation to create and achieve goals, quality of care, and barriers to care using regression models accounting for within-PCP clustering., Results: Of 113 eligible PCPs caring for 330 enrolled patients, 87 PCPs (77%) responded to surveys about 245 (74%) enrolled patients. Intervention patients were more likely to be perceived by PCPs as activated to create and achieve goals for chronic care when compared with UC patients (standardized effect size, ATSM vs UC, +0.41, p = 0.01; GMV vs UC, +0.31, p = 0.05). Primary care providers rated quality of care as higher for patients exposed to ATSM compared to UC (odds ratio 3.6, p < 0.01). Compared with GMV patients, ATSM patients were more likely to be perceived by PCPs as overcoming barriers related to limited English proficiency (82% ATSM vs 44% GMV, p = 0.01) and managing medications (80% ATSM vs 53% GMV, p = 0.01)., Conclusions: Primary care providers perceived that patients receiving ATSM support had overcome barriers, participated more actively, and received higher quality diabetes care. These views of clinician stakeholders lend additional evidence for the potential to upscale ATSM more broadly to support PCPs in their care of diverse, multilinguistic populations., (© 2012 Diabetes Technology Society.)

Myocardial hypoxia is a major factor in the pathology of cardiac ischemia and myocardial infarction. Hypoxia also occurs in microvascular disease and cardiac hypertrophy, and is thought to be a prime determinant of the progression to heart failure, as well as the driving force for compensatory angiogenesis. The non-invasive delineation and quantification of hypoxia in cardiac tissue therefore has the potential to be an invaluable experimental, diagnostic and prognostic biomarker for applications in cardiology. However, at this time there are no validated methodologies sufficiently sensitive or reliable for clinical use. PET imaging provides real-time spatial information on the biodistribution of injected radiolabeled tracer molecules. Its inherent high sensitivity allows quantitative imaging of these tracers, even when injected at sub-pharmacological (≥pM) concentrations, allowing the non-invasive investigation of biological systems without perturbing them. PET is therefore an attractive approach for the delineation and quantification of cardiac hypoxia and ischemia. In this review we discuss the key concepts which must be considered when imaging hypoxia in the heart. We summarize the PET tracers which are currently available, and we look forward to the next generation of hypoxia-specific PET imaging agents currently being developed. We describe their potential advantages and shortcomings compared to existing imaging approaches, and what is needed in terms of validation and characterization before these agents can be exploited clinically., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Given that HIV-protease inhibitors (HIV-PIs) are substrates/inhibitors of the multidrug transporter ABCB1, can induce ABCB1 expression, and are used in combination with doxorubicin for AIDS-Kaposi's Sarcoma (KS) treatment, the role that ABCB1 plays in mediating multidrug resistance (MDR) in a fully transformed KS cell line (SLK) was explored., Methods: The KS cells were exposed to both acute and chronic treatments of physiological concentrations of different HIV-PIs (indinavir, nelfinavir, atazanavir, ritonavir, or lopinavir), alone or together with doxorubicin. The ABCB1 mRNA and protein expression levels were then assessed by qRT-PCR and western blotting, flow cytometry, and immunofluorescence., Results: Chronic treatment of SLK cells with one of the five HIV-PIs alone or together resulted in increased resistance to doxorubicin. Co-treatment with one of the HIV-PIs in combination with doxorubicin resulted in a synergistic increase in resistance to doxorubicin, and the degree of resistance was found to correlate with the expression of ABCB1. The SLK cells were also revealed to be cross-resistant to the structurally unrelated drug paclitaxel., Conclusion: These studies suggest that ABCB1 is primarily responsible for mediating MDR in SLK cells selected with either HIV-PIs alone or in combination with doxorubicin. Therefore, the roles that ABCB1 and drug cocktails play in mediating MDR in KS in vivo should be evaluated.

Human Papillomavirus 16 (HPV-16) has been identified as the causative agent of 50% of cervical cancers and many other HPV-associated tumors. The transforming potential/tumor maintenance capacity of this high risk HPV is mediated by two viral oncoproteins, E6 and E7, making them attractive targets for therapeutic vaccines. Of 21 E6 and E7 peptides computed to bind HLA-A*0201, 10 were confirmed through TAP-deficient T2 cell HLA stabilization assay. Those scoring positive were investigated to ascertain which were naturally processed and presented by surface HLA molecules for CTL recognition. Because IFNγ ELISpot frequencies from healthy HPV-exposed blood donors against HLA-A*0201-binding peptides were unable to identify specificities for tumor targeting, their physical presence among peptides eluted from HPV-16-transformed epithelial tumor HLA-A*0201 immunoprecipitates was analyzed by MS(3) Poisson detection mass spectrometry. Only one epitope (E7(11-19)) highly conserved among HPV-16 strains was detected. This 9-mer serves to direct cytolysis by T cell lines, whereas a related 10-mer (E7(11-20)), previously used as a vaccine candidate, was neither detected by MS(3) on HPV-transformed tumor cells nor effectively recognized by 9-mer specific CTL. These data underscore the importance of precisely defining CTL epitopes on tumor cells and offer a paradigm for T cell-based vaccine design.

Background: Little is known about adverse events (AEs) that occur between physician visits for ambulatory chronic disease patients. An automated telephone self-management support programme for a diverse population of diabetes patients was implemented to capture AEs, describe the self-management domains from which they emanate and explore contributing causes., Methods: AEs and potential AEs (PotAEs) were identified among 111 ethnically diverse diabetes patients. An AE is an injury that results from either medical management or patient self-management; a PotAE is an unsafe state likely to lead to an event if it persists without intervention. Medical record reviews were conducted to ascertain which self-management domain was involved with the event and to explore contributing causes., Results: Among the 111 patients, 86% had at least one event detected over the 9-month observation period. 111 AEs and 153 PotAEs were identified. For all events, medication management was the most common domain (166 events, 63%). Only 20% of events reflected a single contributing cause; in the remaining 80%, a combination of system, clinician and patient factors contributed to their occurrence. Patient actions were implicated in 205 (77%) events, systems issues in 183 (69%) events and inadequate physician-patient communication in 155 (59%) events. Aside from communication, primary care clinician actions contributed to the occurrence of the event in only 16 cases (6%)., Conclusions: Our findings reveal a complex safety ecology, with multiple contributing causes for AEs and PotAEs among ambulatory diabetes patients. Moreover, patients themselves seem to be key drivers of safety and of AEs, suggesting that patient-level self-management support and patient-centred communication are critical to AE prevention.

An interdisciplinary investigation, involving environmental geochemists, epidemiologists, nurses, and anthropologists, was undertaken to determine the contamination source and pathway of an on-going outbreak of lead poisoning among migrants originating from Zimatlán, Oaxaca, Mexico and living in Seaside, California, and among their US-born children. An initial investigation in Seaside identified grasshopper foodstuff ("chapulines") imported from Mexico and consumed as snacks, as containing alarmingly high lead concentrations (up to 2300 mg/kg). The focus in the present work concentrates on the Oaxacan area of origin of the problem in Mexico, and two potential sources of contamination were investigated: wind-borne dusts from existing mine residues as potential contaminants of soil, plant, and fauna; and food preparation practices using lead-glazed ceramic cookware. Over a three year period, sampling was conducted in Oaxaca using community-level sampling and also targeted sampling with families of cases with lead poisoning in California. In addition to fresh field chapulines, we analyzed for total lead: soil, water, mine residues, and plant materials, both from areas adjacent to or at an abandoned waste site containing mine tailings, and from fields where chapulines are collected; foodstuffs gathered in community markets or in a food transport business; and foodstuffs and cookware gathered from relatives of case families in California. Also, selected new and used lead-glazed clay cookware was extracted for lead, using 0.02 M citric acid and with 4% acetic acid. The results indicated significant presence of lead in mine wastes, in specific foodstuffs, and in glazed cookware, but no extensive soil contamination was identified. In-situ experiments demonstrated that lead incorporation in food is made very efficient through grinding of spices in glazed cookware, with the combination of a harsh mechanical action and the frequent presence of acidic lime juice, but without heating, resulting in high but variable levels of contamination.

The authors examined whether tailored self-management support (SMS) strategies reach patients in a safety net system and explored variation by language, literacy, and insurance. English-, Spanish-, and Cantonese-speaking diabetes patients were randomized to weekly automated telephone disease management (ATDM) or monthly group medical visits. The SMS programs employ distinct communication methods but share common objectives, including behavioral "action plans." Reach was measured using three complementary dimensions: (a) participation among clinics, clinicians, and patients; (b) patient representativeness; and (c) patient engagement with SMS. Participation rates were high across all levels and preferentially attracted Spanish-language speakers, uninsured, and Medicaid recipients. Although both programs engaged a significant proportion in action planning, ATDM yielded higher engagement, especially among those with limited English proficiency and limited literacy. These results provide important insights for health communication and translational research with respect to realizing the public health benefits of SMS and can inform system-level planning to reduce health disparities.

Challenges in identifying children exposed prenatally to ethanol necessitate the development of a biomarker for neonates at risk for fetal alcohol spectrum disorder. Meconium fatty acid ethyl esters (FAEE), products of nonoxidative ethanol metabolism, have been established as a novel biomarker of fetal ethanol exposure. We present the first application of this biomarker to a population-based sample in Canada. Six-hundred eighty-two meconium specimens were anonymously collected in the region of Grey Bruce, Ontario, Canada. Meconium FAEE were extracted by liquid-liquid and solid-phase extraction and analyzed by gas chromatography with flame-ionization detection confirmed by gas chromatography with mass spectrometry. We measured ethyl palmitate (E16:0), ethyl palmitoleate (E16:1), ethyl stearate (E18:0), ethyl oleate (E18:1), ethyl linoleate (E18:2), ethyl linolenate (E18:3), and ethyl arachidonate (E20:4). Seventeen of 682 meconium samples tested positive for significant prenatal ethanol exposure (>2.0 nmol/g). FAEE analysis detected fivefold more ethanol-exposed pregnancies than standard postpartum questionnaires in this population (2.5% versus 0.5%) (P < 0.001). The prevalence of ethanol-exposed pregnancies was consistent with Centers for Disease Control and Prevention estimates of "frequent" prenatal drinking and previously published estimates of fetal alcohol spectrum disorder disease prevalence in the general North American population. The FAEE concentrations of negative (95% confidence interval, 0.38-0.49 nmol/g) versus positive (95% confidence interval, 7.74-151.28 nmol/g) samples were distinct, further demonstrating the specificity of this biomarker in determining significant prenatal ethanol exposure. Meconium FAEE analysis demonstrates a fivefold increase in sensitivity over currently used methods of self-report-based screening in Ontario for the detection of ethanol-exposed pregnancies in a clinical setting.

Objective: To determine the extent to which Medicaid managed care (MMC) organizations are engaged in chronic disease care management (CDCM), tailor CDCM for diverse populations, or plan to expand CDCM., Study Design: Web-based survey of 23 eligible California MMC health plan executives in fall 2005., Methods: Frequency distributions of survey responses., Results: Nineteen (83%) of 23 executives responded, representing 2.5 million beneficiaries. Eighteen (95%) MMC plans reported implementing 1 or more elements of CDCM. Although plans used a wide range of CDCM strategies to reach performance goals, most implemented provider awareness activities such as offering guidelines or disease-specific feedback to physician groups. More than half of the plans reported interest in expanding CDCM to include more active interventions such as disease registries, pay for performance, telephone counseling to patients, and other self-management support programs. Few plans reported tailoring their CDCM to vulnerable member populations such as those with limited literacy or limited English proficiency. Executives reported that insufficient financial resources at the plan level, lack of organizational leadership and commitment in physician organizations, and limited information technology in physician offices were barriers to CDCM expansion., Conclusions: California MMC health plans reported substantial interest in CDCM and a desire to increase CDCM. Representatives reported intentions to expand to strategies that more directly engage providers and patients. To ensure that the growing number of vulnerable enrollees with chronic disease receive high-quality care, policy efforts should focus on enabling MMC health plans to more consistently implement and target population-based strategies such as CDCM.

The morphology of antigen-presenting dendritic cells (DCs) is characterized by the presence of numerous long dendrites. The formation of these processes is shown to require the interaction between the beta1-integrin (CD29) on the surface of the DCs and fibronectin in the extracellular matrix. This interaction occurs at focal contacts formed at the tips of dendrites, which contain high concentrations of the beta1-integrins, actin and the cytoskeletal proteins vinculin, paxillin and talin. Dendrites contain an extensive microtubule (MT) network, and are retracted in the presence of the MT inhibitor colchicine, suggesting that MTs are essential for dendrite stability. The dendritic morphology is shown to contribute directly to an enhanced ability to capture dendritic cell specific ICAM-3 grabbing nonintegrin (DC-SIGN)-coated beads. Time-lapse photography demonstrates that dendrites are highly dynamic structures, with cells extending and retracting multiple dendrites in different directions over a 3-h period. This motility increases the area scanned by an individual DC by over 2-fold. The unusual combination of a dendritic morphology and high motility is likely to play a major role in the efficient function of DCs as sentinels of the immune system.