Perceptual factors influence visual search for meaningful symbols in individuals with intellectual disabilities and down syndrome or autism spectrum disorders
Augmentative and alternative communication (AAC) systems often supplement oral communication for individuals with intellectual and communication disabilities. Research with preschoolers without disabilities has demonstrated that two visual-perceptual factors influence speed and/or accuracy of finding a target: the internal color and spatial organization of symbols. Twelve participants with Down syndrome and 12 with autism spectrum disorders (ASDs) completed two search tasks. In one, the symbols were clustered by internal color; in the other, the identical symbols had no arrangement cue. Visual search was superior in participants with ASDs compared to those with Down syndrome. In both groups, responses were significantly faster when the symbols were clustered by internal color. Construction of aided AAC displays may benefit from attention to their physical and perceptual features.
Eye-tracking Measures Reveal How Changes in the Design of Aided AAC Displays Influence the Efficiency of Locating Symbols by School-Aged Children without Disabilities
PURPOSE: Many individuals with communication impairments use aided AAC systems involving letters, words, or line-drawings, that rely on the visual modality. It seems reasonable to suggest that display design should incorporate information about how users attend to and process visual information. The organization of AAC symbols can influence the speed and accuracy with which children select a target symbol on a display. This research examined why some displays facilitate responding.
METHOD: Eye-tracking technology recorded point-of-gaze while nondisabled children engaged in a visual search task with two AAC displays. In one, symbols sharing an internal color were clustered together. In the other, like-colored symbols were distributed. Dependent measures were latency to fixate on the target compared to distracters, and the number of fixations to target and distracters.
RESULTS: Participants were significantly slower to fixate on the target when like-colored symbols were distributed, with a significant increase in the number of fixations to distracters that did not share color with the target.
CONCLUSIONS: Efficient search was related to minimizing fixations to non-relevant distracters. Vulnerability to distraction can be a significant problem in individuals with disabilities who use AAC. Minimizing the intrusion of such distraction may therefore of importance in AAC display design.
Rapid generation of balanced trial distributions for discrimination learning procedures: A technical note
We describe novel computer algorithms for rapid, sometimes virtually instantaneous generation of trial sequences needed to instrument many behavioral research procedures. Implemented on typical desktop or laptop computers, the algorithms impose constraints to forestall development of undesired stimulus control by position, recent trial outcomes, and other variables that could impede simple and conditional discrimination learning. They yield trial-by-trial lists of sequences that can serve (1) as inputs to procedure control software or (2) in generating templates for constructing sessions for implementation by hand or machine.
BACKGROUND: There is much interest in understanding how using bundled primary care payments to support a patient-centered medical home (PCMH) affects total medical costs.
RESEARCH DESIGN AND SUBJECTS: We compare 2008-2010 claims and eligibility records on about 10,000 patients in practices transforming to a PCMH and receiving risk-adjusted base payments and bonuses, with similar data on approximately 200,000 patients of nontransformed practices remaining under fee-for-service reimbursement.
METHODS: We estimate the treatment effect using difference-in-differences, controlling for trend, payer type, plan type, and fixed effects. We weight to account for partial-year eligibility, use propensity weights to address differences in exogenous variables between control and treatment patients, and use the Massachusetts Health Quality Project algorithm to assign patients to practices.
RESULTS: Estimated treatment effects are sensitive to: control variables, propensity weighting, the algorithm used to assign patients to practices, how we address differences in health risk, and whether/how we use data from enrollees who join, leave, or change practices. Unadjusted PCMH spending reductions are 1.5% in year 1 and 1.8% in year 2. With fixed patient assignment and other adjustments, medical spending in the treatment group seems to be 5.8% (P=0.20) lower in year 1 and 8.7% (P=0.14) lower in year 2 than for propensity-weighted, continuously enrolled controls; the largest proportional 2-year reduction in spending occurs in laboratory test use (16.5%, P=0.02).
CONCLUSIONS: Although estimates are imprecise because of limited data and quasi-experimental design, risk-adjusted bundled payment for primary care may have dampened spending growth in 3 practices implementing a PCMH.
Relationship among circulating inflammatory proteins, platelet gene expression, and cardiovascular risk
OBJECTIVE: Cardiovascular disease is a complex disorder influenced by interactions of genetic variants with environmental factors. However, there is no information from large community-based studies examining the relationship of circulating cell-specific RNA to inflammatory proteins. In light of the associations among inflammatory biomarkers, obesity, platelet function, and cardiovascular disease, we sought to examine the relationships of C-reactive protein (CRP) and interleukin-6 (IL-6) to the expression of key inflammatory transcripts in platelets.
APPROACH AND RESULTS: We quantified circulating levels of CRP and IL-6 in 1625 participants of the Framingham Heart Study (FHS) Offspring cohort examination 8 (mean age, 66.6 ± 6.6 years; 46% men). We measured the expression of 15 relevant genes by high-throughput quantitative reverse transcriptase polymerase chain reaction from platelet-derived RNA and used multivariable regression to relate serum concentrations of CRP and IL-6 with gene expression. Levels of CRP and IL-6 were associated with 10 of the 15 platelet-derived inflammatory transcripts, ALOX5, CRP, IFIT1, IL6, PTGER2, S100A9, SELENBP1, TLR2, TLR4, and TNFRSF1B (P<0.001). Associations between platelet mRNA expression with CRP and IL-6 persisted after multivariable adjustment for potentially confounding factors. Six genes positively associated with CRP or IL-6 in the FHS sample were also upregulated in megakaryocytes in response to CRP or IL-6 exposure.
CONCLUSIONS: Our data highlight the strong connection between the circulating inflammatory biomarkers CRP and IL-6 and platelet gene expression, adjusting for cardiovascular disease risk factors. Our results also suggest that body weight may directly influence these associations.
Diversity of T cell epitopes in Plasmodium falciparum circumsporozoite protein likely due to protein-protein interactions
Circumsporozoite protein (CS) is a leading vaccine antigen for falciparum malaria, but is highly polymorphic in natural parasite populations. The factors driving this diversity are unclear, but non-random assortment of the T cell epitopes TH2 and TH3 has been observed in a Kenyan parasite population. The recent publication of the crystal structure of the variable C terminal region of the protein allows the assessment of the impact of diversity on protein structure and T cell epitope assortment. Using data from the Gambia (55 isolates) and Malawi (235 isolates), we evaluated the patterns of diversity within and between epitopes in these two distantly-separated populations. Only non-synonymous mutations were observed with the vast majority in both populations at similar frequencies suggesting strong selection on this region. A non-random pattern of T cell epitope assortment was seen in Malawi and in the Gambia, but structural analysis indicates no intramolecular spatial interactions. Using the information from these parasite populations, structural analysis reveals that polymorphic amino acids within TH2 and TH3 colocalize to one side of the protein, surround, but do not involve, the hydrophobic pocket in CS, and predominately involve charge switches. In addition, free energy analysis suggests residues forming and behind the novel pocket within CS are tightly constrained and well conserved in all alleles. In addition, free energy analysis shows polymorphic residues tend to be populated by energetically unfavorable amino acids. In combination, these findings suggest the diversity of T cell epitopes in CS may be primarily an evolutionary response to intermolecular interactions at the surface of the protein potentially counteracting antibody-mediated immune recognition or evolving host receptor diversity.
When, Where and How Osteoporosis-Associated Fractures Occur: An Analysis from the Global Longitudinal Study of Osteoporosis in Women (GLOW)
Objective: To examine when, where and how fractures occur in postmenopausal women.
Methods: We analyzed data from the Global Longitudinal Study of Osteoporosis in Women (GLOW), including women aged ≥55 years from the United States of America, Canada, Australia and seven European countries. Women completed questionnaires including fracture data at baseline and years 1, 2 and 3.
Results: Among 60,393 postmenopausal women, 4122 incident fractures were reported (86% non-hip, non-vertebral [NHNV], 8% presumably clinical vertebral and 6% hip). Hip fractures were more likely to occur in spring, with little seasonal variation for NHNV or spine fractures. Hip fractures occurred equally inside or outside the home, whereas 65% of NHNV fractures occurred outside and 61% of vertebral fractures occurred inside the home. Falls preceded 68–86% of NHNV and 68–83% of hip fractures among women aged ≤64 to ≥85 years, increasing with age. About 45% of vertebral fractures were associated with falls in all age groups except those ≥85 years, when only 24% occurred after falling.
Conclusion: In this multi-national cohort, fractures occurred throughout the year, with only hip fracture having a seasonal variation, with a higher proportion in spring. Hip fractures occurred equally within and outside the home, spine fractures more often in the home, and NHNV fractures outside the home. Falls were a proximate cause of most hip and NHNV fractures. Postmenopausal women at risk for fracture need counseling about reducing potentially modifiable fracture risk factors, particularly falls both inside and outside the home and during all seasons of the year.
Genetic manipulation in enterohemorrhagic E. coli O157:H7 is currently restricted to recombineering, a method that utilizes the recombination system of bacteriophage lambda, to introduce gene replacements and base changes inter alia into the genome. Bacteriophage 933W is a prophage in E. coli O157:H7 strain EDL933, which encodes the genes ( stx2AB) for the production of Shiga toxin which is the basis for the potentially fatal Hemolytic Uremic Syndrome in infected humans. We replaced the stx2AB genes with a kanamycin cassette using recombineering. After induction of the prophage by ultra-violet light, we found that bacteriophage lysates were capable of transducing to wildtype, point mutations in the lactose, arabinose and maltose genes. The lysates could also transduce tetracycline resistant cassettes. Bacteriophage 933W is also efficient at transducing markers in E. coli K-12. Co-transduction experiments indicated that the maximal amount of transferred DNA was likely the size of the bacteriophage genome, 61 kB. All tested transductants, in both E. coli K-12 and O157:H7, were kanamycin-sensitive indicating that the transducing particles contained host DNA.
Clarifying the role of the mental health peer specialist in Massachusetts, USA: insights from peer specialists, supervisors and clients
Mental health peer specialists develop peer-to-peer relationships of trust with clients to improve their health and well-being, functioning in ways similar to community health workers. Although the number of peer specialists in use has been increasing, their role in care teams is less defined than that of the community health worker. This qualitative study explored how the peer specialist role is defined across different stakeholder groups, the expectations for this role and how the peer specialist is utilised and integrated across different types of mental health services. Data were collected through interviews and focus groups conducted in Massachusetts with peer specialists (N = 44), their supervisors (N = 14) and clients (N = 10) between September 2009 and January 2011. A consensus coding approach was used and all data outputs were reviewed by the entire team to identify themes. Peer specialists reported that their most important role is to develop relationships with clients and that having lived mental health experience is a key element in creating that bond. They also indicated that educating staff about the recovery model and peer role is another important function. However, they often felt a lack of clarity about their role within their organisation and care team. Supervisors valued the unique experience that peer specialists bring to an organisation. However, without a defined set of expectations for this role, they struggled with training, guiding and evaluating their peer specialist staff. Clients reported that the shared lived experience is important for the relationship and that working with a peer specialist has improved their mental health. With increasing support for person-centred integrated healthcare delivery models, the demand for mental health peer specialist services will probably increase. Therefore, clearer role definition, as well as workforce development focused on team orientation, is necessary for peer specialists to be fully integrated and supported in care teams.
Resistance to the BRAF inhibitor vemurafenib poses a significant problem for the treatment of BRAFV600E-positive melanomas. It is therefore critical to prospectively identify all vemurafenib resistance mechanisms prior to their emergence in the clinic. The vemurafenib resistance mechanisms described to date do not result from secondary mutations within BRAFV600E. To search for possible mutations within BRAFV600E that can confer drug resistance, we developed a systematic experimental approach involving targeted saturation mutagenesis, selection of drug-resistant variants, and deep sequencing. We identified a single nucleotide substitution (T1514A, encoding L505H) that greatly increased drug resistance in cultured cells and mouse xenografts. The kinase activity of BRAFV600E/L505H was higher than that of BRAFV600E, resulting in cross-resistance to a MEK inhibitor. However, BRAFV600E/L505H was less resistant to several other BRAF inhibitors whose binding sites were further from L505 than that of PLX4720. Our results identify a novel vemurafenib-resistant mutant and provide insights into the treatment for melanomas bearing this mutation.
Healthy People 2020 Structured Evidence Queries: Facilitating Access to Published Research for Public Health Planning and Policy Development
Healthy People 2020 (HP2020) provides national objectives to guide health promotion and disease prevention efforts in the United States. Public health professionals and policy makers may have limited time to identify relevant research evidence to inform program planning and policy development. The National Library of Medicine (NLM) recognized the need to reduce the time and increase the precision of finding research literature to support the development of evidence-based actions to achieve HP2020 objectives. NLM collaborated with the HHS Office of Disease Prevention and Health Promotion to develop pre-formulated search strategies - structured evidence queries (SEQs) - of the PubMed database to make research evidence related to HP2020 objectives easier to find. The search queries were developed by librarians, working in consultation with subject matter experts in public health. The HP2020 SEQ website is organized by HP2020 topic areas and provides PubMed search results for HP2020 objectives including the Leading Health Indicators, a subset of high-priority health issues that represent significant threats to the public’s health. The PubMed search strategies were designed to return a manageable number of relevant citations for busy public health professionals to review. The search strategies can be modified in PubMed to address particular practice and research needs. Information to help users learn more about PubMed, obtain full-text copies of articles, and find additional resources for public health practice are provided in the FAQs section of the site. The resource was developed as a result of an effective partnership between librarians, public health professionals, and subject experts.
Modulating Influenza and Heparin Binding Viruses’ Pathogenesis with Extrinsic Receptor Decoy Liposomes: A Dissertation
Influenza is a severe disease in humans and animals, causing upwards of 40,000 deaths every year in America alone. Influenza A virus (IAV) also causes periodic pandemics every 10 to 50 years, killing millions of people. Despite this, very few effective therapies are available. All strains of IAV are prone to developing resistance to antibodies due to the high mutation rate in the viral genome. Because of this mutation rate, a yearly vaccine must be generated before every flu season, and efficacy varies year to year. IAV has also mutated to escape several of the clinically-approved small molecule inhibitors. A therapeutic agent that targets a highly conserved region of the virus could bypass resistance and also be effective against multiple strains of IAV. IAV attachment is mediated by many individually weak hemagglutinin–sialic acid interactions that all together make a strong attachment to a host cell. Polymerized sialic acid analogs can recreate these interactions and block infection. However, they are not ideal therapeutics due to solubility issues and in vivo toxicity. We used liposomes as a novel means for delivery of the sialic acid-containing glycan, sialylneolacto-N-tetraose c (LSTc). LSTcbearing decoy liposomes form multivalent, polymer-like interactions with IAV. Decoy liposomes competitively bind IAV in hemagglutination inhibition assays and inhibit infection of target cells in a dose-dependent manner. LSTc decoy liposomes co-localize with IAV, while control liposomes do not. Inhibition is specific, as inhibition of Sendai virus and respiratory syncytial virus is not observed. In contrast, monovalent LSTc does not bind IAV or inhibit infectivity. LSTc decoy liposomes prevent the spread of IAV during multiple rounds of replication in vitro and extend survival of mice challenged with a lethal dose of virus. Considering the conservation of the hemagglutinin binding pocket and the ability of decoy liposomes to form high-avidity interactions with IAV hemagglutinin, our decoy liposomes have potential as a new therapeutic agent against emerging strains.
The dynamics of T cell responses have been extensively studied during single virus infection of naïve mice. During a viral infection, viral antigen is presented in the context of MHC class I molecules on the surface of infected cells. Activated CD8 T cells that recognized viral antigens mediate clearance of virus through lysis of these infected cells. We hypothesize that the balance between the replicating speed of the virus and the efficiency at which the T cell response clears the virus is key in determining the disease outcome of the host. Lower T cell efficiency and delayed viral clearance can lead to extensive T cellmediated immunopathology and death in some circumstances. To examine how the efficiency of the immune response would impact immunopathology we studied several viral infection models where T cell responses were predicted to be less than optimal: 1. a model of co-infection with two viruses that contain a crossreactive epitope, 2. a viral infection model where a high dose infection is known to induce clonal exhaustion of the CD8 T cell response, 3. a neonatal virus infection model where the immune system is immature and 4. A model of beneficial heterologous immunity and T cell crossreactivity where mice are immunized as neonates when the T cell pool is still developing.
Model 1. Simultaneous co-infections are common and can occur from mosquito bites, contaminated needle sticks, combination vaccines and the simultaneous administration of multiple vaccines. Using two distantly related arenaviruses, lymphocytic choriomeningitis virus (LCMV) and Pichinde virus (PICV), we questioned if immunological T cell memory and subsequent protection would be altered following a simultaneous co-infection, where two immune responses are generated within the same host at the same time. Coinfection with these two viruses, which require CD8 T cell responses to clear, resulted in decreased immune protection and enhanced immunopathology after challenge with either virus. After primary co-infection, each virus-specific immune response impacted the other as they competed within the same host and resulted in several significant differences in the CD8 T cell responses compared to mice infected with a single virus. Co-infected mice had a dramatic decrease in the overall size of the LCMV-specific CD8 T cell response and variability in which virus-specific response dominated, along with skewing in the immunodominance hierarchies from the normal responses found in single virus infected mice. The reduction in the number of LCMV-specific CD8 memory T cells, specifically cells with an effector memory-like phenotype, was associated with higher viral loads and increased liver pathology in co-infected mice upon LCMV challenge. The variability in the immunodominance hierarchies of co-infected mice resulted in an enhanced cross-reactive response in some mice that mediated enhanced immune-mediated fat pad pathology during PICV challenge. In both viral challenge models, an ineffective memory T cell response in co-infected mice facilitated increased viral replication, possibly leading to enhanced and prolonged accumulation of secondary effector T cells in the tissues, thereby leading to increased immune pathology. Thus, the magnitude and character of memory CD8 T cell responses in simultaneous co-infections differed substantially from those induced by single immunization. This has implications for the design of combination vaccines and scheduling of simultaneous immunizations.
Model 2. The balance between protective immunity and immunopathology often determines the fate of the virus-infected host. Several human viruses have been shown to induce a wide range of severity of disease. Patients with hepatitis B virus (HBV), for example, show disease progression ranging from acute resolving infection to a persistent infection and fulminant hepatitis. Certain rapidly replicating viruses have the ability to clonally exhaust the T cell response, such as HBV and hepatitis C virus (HCV) in humans and the clone 13 strain of LCMV in mice. How rapidly virus is cleared is a function of initial viral load, viral replication rate, and efficiency of antigen-specific T cells. By infecting mice with three different inocula of LCMV clone 13, we questioned how the race between virus replication and T cell responses could result in different disease outcomes. A low dose of LCMV generated efficient CD8 T effector cells, which cleared the virus with minimal lung and liver pathology. A high dose of LCMV resulted in clonal exhaustion of T cell responses, viral persistence and little immunopathology. An intermediate dose only partially exhausted the CD8 T cell responses and was associated with significant mortality, and the surviving mice developed viral persistence and massive immunopathology, including necrosis of the lungs and liver. This was a T cell-mediated disease as T cell-deficient mice had no pathology and became persistently infected like mice infected with a high dose of LCMV clone 13. This suggests that for non-cytopathic viruses like LCMV, HCV and HBV, clonal exhaustion may be a protective mechanism preventing severe immunopathology and death.
Model 3. Newborns are more susceptible to infections due to their lack of immunological memory and under-developed immune systems. Passive maternal immunity helps protect neonates until their immune systems have matured. We questioned if a noncytolytic virus that produces strong T cell responses in adult mice would also induce an equally effective response in neonatal mice. Neonates were infected with very low doses of LCMV Armstrong and surprisingly the majority succumbed to infection between days 7-11, which is the peak of the T cell response in adult mice infected with LCMV. Death was caused by T cell-dependent pathology and not viral load as 100% of T cell deficient neonates survived with minimal lung and liver pathology. This is similar to the adult model of medium dose LCMV clone 13, but T cell responses in neonates were not partially clonal exhausted. Furthermore, surviving neonates were not persistently infected, clearing virus by day 14 post infection. In adult mice direct intracranial infection leads to LCMV replication and CD8 T cell infiltration in the central nervous system (CNS), causing CD8 T cell-mediated death. However, this does not occur in adults during LCMV intraperitoneal (ip) infections. We questioned if unlike adults LCMV could be gaining access to the CNS in neonates following ip infection. Replicating LCMV was found in the brain of neonates after day 5 post infection along with virus-specific CD8 T cells producing IFNγ at day 9 post infection. Neonates lacking perforin had complete survival when followed until day 14 post infection, suggesting perforin-mediated T cell-dependent immunopathology within the CNS of neonates was causing death after LCMV infection. Passive immunity from LCMV-immune mothers also protected 100% of pups from death by helping control viral load early in infection. We believe that the maternal antibody compensates for the immature innate immune response of neonates and controls viral replication early so the neonatal T cell response induced less immunopathology. Neonates are commonly thought to have less functional immune systems, but these results show that neonates are capable of producing strong T cell responses that contribute to increased mortality.
Model 4. Due to their enhanced susceptibility to infection neonatal and infant humans receive multiple vaccines. Several non-specific effects from immunizations have been observed, for example, measles or Bacillus Calmette- Guerin (BCG) vaccines have been linked to decreased death of children from infections other than measles virus or tuberculosis. These studies mirror the concepts of beneficial heterologous immunity, where previous immunization with an unrelated pathogen can result in faster viral clearance. LCMV-immune mice challenged with vaccinia virus (VV) have lower viral loads then naïve mice and survive lethal infections, but some mice do develop fat pad immunopathology in the form of panniculitis or acute fatty necrosis (AFN). We questioned how immunological T cell memory formed during the immature neonatal period would compare to memory generated in fully mature adults during a heterologous viral challenge. Mice immunized as neonates had comparable reduction in VV load and induction of AFN, indicating that heterologous immunity is established during viral infections early in life. Interestingly, the LCMV-specific memory populations that expanded in mice immunized as neonates differed from that of mice immunized as adults. In adult mice 50% of the mice have an expansion of LCMVNP205- specific CD8 T cells while the majority of neonates expanded the LCMVGP34- specific CD8 T cell pool. This alteration in dominant crossreactivities may be due to the limited T cell receptor repertoire of neonatal mice. In naïve neonatal mice we found altered Vβ repertoires within the whole CD8 T cell pool. Furthermore, there was altered Vβ usage within virus-specific responses compared to adult mice and a wide degree of variability between individual neonates, suggesting enhanced private specificity of the TCR repertoire. Beneficial heterologous immunity is maintained in neonates, but there was altered usage of crossreactive responses.
As neonatal mice were found to be so sensitive to LCMV infection we questioned if neonates could control another arena virus that did not replicate as efficiently in mice, PICV. Unlike LCMV infection, neonatal mice survived infection with PICV even with adult-like doses. However, viral clearance was protracted in neonates compared to adults, but was cleared from fat pad and kidney by day 11 post infection. The peak of the CD8 T cell response was similarly delayed. PICV infected neonates showed dose-dependent PICV-specific CD8 T cell responses,
which were similar to adult responses by frequency, but not total number. As with LCMV infection there were changes in immunodominance hierarchies in neonates. Examination of the immunodominance hierarchies of PICV-infected neonates showed that there were adult-like responses to the dominant NP38- specific response, but a loss of the NP122-specific response. Six weeks post neonatal infection mice were challenged with LCMV Armstrong and there was a strong skewing of the PICV immunodominance hierarchy to the crossreactive NP205-specific response. These data further support the hypothesis that heterologous immunity and crossreactivity develop following neonatal immunization, much as occurs in adults, although TCR repertoire and crossreactive patterns may differ.
Changing the balance between T cell efficiency and viral load was found to altered the severity of the developing immunopathology after viral infection.
Uncovering the evidence: Systematic review of interventions to reduce oral health disparities between adults with Intellectual Disability and the general population
Oral health is a public health concern for people with intellectual or developmental disabilities (I/DD). Research consistently shows that the population with I/DD experiences poorer oral hygiene, higher prevalence and severity of periodontal disease, and higher incidence of untreated caries when compared to the general population. Poor oral health can cause chronic pain, affect the ability to eat and communicate, and adversely affect physical health and quality of life. Intervention strategies include enhanced prevention, increased routine care, expanded insurance coverage, and training for dentists and hygienists. Research is needed to identify the most effective interventions. A standard systematic literature review for evidence-based practices is not adequate for identifying and evaluating the evidence in areas such as health policy and individual health behaviors. This presentation describes the structured processes used in uncovering evidence where there is limited published literature that includes 1) the I/DD population and 2) traditional scientific reviews of interventions addressing their oral health. By adapting a transdisciplinary conceptual model, which could be applied to a multitude of disciplines, we identify the best available evidence as collected through a conventional systematic review, allowing for additional emphasis on the personal, social and environmental factors that affect the I/DD population. The process includes search strategies to include peer reviewed and gray literature, along with other associated programs, policies, and practices, resulting in a unique evidence base from varied sources. Additionally, we frame and refine a formal plan to review the outcomes and establish a level of evidence for the identified interventions.
Chronic kidney disease and outcomes in heart failure with preserved versus reduced ejection fraction: the Cardiovascular Research Network PRESERVE Study
BACKGROUND: There is scant evidence on the effect that chronic kidney disease (CKD) confers on clinically meaningful outcomes among patients with heart failure with preserved left ventricular ejection fraction (HF-PEF).
METHODS AND RESULTS: We identified a community-based cohort of patients with HF. Electronic medical record data were used to divide into HF-PEF and reduced left ventricular EF on the basis of quantitative and qualitative estimates. Level of CKD was assessed by estimated glomerular filtration rate (eGFR) and by dipstick proteinuria. We followed patients for a median of 22.1 months for outcomes of death and hospitalization (HF-specific and all-cause). Multivariable Cox regression estimated the adjusted relative-risk of outcomes by level of CKD, separately for HF-PEF and HF with reduced left ventricular EF. We identified 14 579 patients with HF-PEF and 9762 with HF with reduced left ventricular EF. When compared with patients with eGFR between 60 and 89 mL/min per 1.73 m(2), lower eGFR was associated with an independent graded increased risk of death and hospitalization. For example, among patients with HF-PEF, the risk of death was nearly double for eGFR 15 to 29 mL/min per 1.73 m(2) and 7x higher for eGFR/min per 1.73 m(2), with similar findings in those with HF with reduced left ventricular EF.
CONCLUSIONS: CKD is common and an important independent predictor of death and hospitalization in adults with HF across the spectrum of left ventricular systolic function. Our study highlights the need to develop new and effective interventions for the growing number of patients with HF complicated by CKD.
BACKGROUND: Cognitive impairment, highly prevalent in patients with heart failure (HF), increases risk for hospitalization and mortality. However, the course of cognitive change in HF is not well characterized. The purpose of this systematic review was to examine the available evidence longitudinal changes in cognitive function in patients with HF.
METHODS AND RESULTS: A literature search of several electronic databases was performed. Studies published from January 1, 1980, to September 30, 2012, that used validated measures to diagnose HF and assess cognitive function >/=2x in adults with HF were eligible for inclusion. Change in cognitive function was examined in the context of HF treatments applied (eg, medication initiation, left ventricular assist device implantation), length of follow-up, and comparison group. Fifteen studies met eligibility criteria. Significant decline in cognitive function was noted among patients with HF followed up for >1 year. Improvements in cognition were observed among patients with HF undergoing interventions to improve cardiac function (eg, heart transplantation) and among patients examined over short time periods (<1 >year). Studies comparing patients' cognition over time with their own baseline tended to report improvements, whereas studies using a comparison group without HF tended to report declines or stability in cognition over time among patients with HF.
CONCLUSIONS: Patients with HF are at increased risk for cognitive decline, but this risk seems to be modifiable with cardiac treatment. Further research is needed to identify the mechanisms that cause cognitive changes in HF.
IDEAS for a healthy baby--reducing disparities in use of publicly reported quality data: study protocol for a randomized controlled trial
BACKGROUND: Publicly reported performance on quality measures is intended to enable patients to make more informed choices. Despite the growing availability of these reports, patients' use remains limited and disparities exist. Low health literacy and numeracy are two barriers that may contribute to these disparities. Patient navigators have helped patients overcome barriers such as these in other areas, such as cancer care and may prove useful for overcoming barriers to using publicly reported quality data.
METHODS/DESIGN: The goals of this study are: to determine the efficacy of a patient navigator intervention to assist low-income pregnant women in the use of publicly available information about quality of care when choosing a pediatrician; to evaluate the relative importance of factors influencing women's choice of pediatric practices; to evaluate the effect of the intervention on patient engagement in management of their own and their child's health care; and to assess variation in efficacy of the intervention for sub-groups based on parity, age, and race/ethnicity. English speaking women ages 16 to 50 attending a prenatal clinic at a large urban medical center will be randomized to receive an in-person navigator intervention or an informational pamphlet control between 20 to 34 weeks of gestation. The intervention will include in-person guided use of the Massachusetts Health Quality Partners website, which reports pediatric practices' performance on quality measures and patient experience. The primary study outcomes will be the mean scores on a) clinical quality and b) patient experience measures.
DISCUSSION: Successful completion of the study aims will yield important new knowledge about the value of guided website navigation as a strategy to increase the impact of publicly reported quality data and to reduce disparities in use of these data.
TRIAL REGISTRATION: ClinicalTrials.gov #NCT01784575.
PURPOSE: To conduct a synthesis of the literature on methods to evaluate the impacts of FDA regulatory actions and identify best practices for future evaluations.
METHODS: We searched MEDLINE for manuscripts published between January 1948 and August 2011 that included terms related to FDA, regulatory actions, and empirical evaluation; the review additionally included FDA-identified literature. We used a modified Delphi method to identify preferred methodologies. We included studies with explicit methods to address threats to validity and identified designs and analytic methods with strong internal validity that have been applied to other policy evaluations.
RESULTS: We included 18 studies out of 243 abstracts and papers screened. Overall, analytic rigor in prior evaluations of FDA regulatory actions varied considerably; less than a quarter of studies (22%) included control groups. Only 56% assessed changes in the use of substitute products/services, and 11% examined patient health outcomes. Among studies meeting minimal criteria of rigor, 50% found no impact or weak/modest impacts of FDA actions and 33% detected unintended consequences. Among those studies finding significant intended effects of FDA actions, all cited the importance of intensive communication efforts. There are preferred methods with strong internal validity that have yet to be applied to evaluations of FDA regulatory actions.
CONCLUSIONS: Rigorous evaluations of the impact of FDA regulatory actions have been limited and infrequent. Several methods with strong internal validity are available to improve trustworthiness of future evaluations of FDA policies.
OBJECTIVE: The disclosure of medical errors has attracted considerable research interest in recent years. However, the research to date has lacked interdisciplinary dialog, making translation of findings into medical practice challenging. This article lays out the disciplinary perspectives of the fields of medicine, ethics, law and communication on medical error disclosure and identifies gaps and tensions that occur at these interdisciplinary boundaries.
METHODS: This article summarizes the discussion of an interdisciplinary error disclosure panel at the 2012 EACH Conference in St. Andrews, Scotland, in light of the current literature across four academic disciplines.
RESULTS: Current medical, ethical, legal and communication perspectives on medical error disclosure are presented and discussed with particular emphasis on the interdisciplinary gaps and tensions.
CONCLUSION: The authors encourage interdisciplinary collaborations that strive for a functional approach to understanding and improving the disclosure of medical errors with the ultimate goal to improve quality and promote safer medical care.
PRACTICE IMPLICATIONS: Interdisciplinary collaborations are needed to reconcile the needs of the stakeholders involved in medical error disclosure. A particular challenge is the effective translation of error disclosure research into practice. Concrete research questions are provided throughout the manuscript to facilitate a resolution of the tensions that currently impede interdisciplinary progress.