Better Respiratory Education and Treatment Help Empower (BREATHE) study: Methodology and baseline characteristics of a randomized controlled trial testing a transitional care program to improve patient-centered care delivery among chronic obstructive pulmonary disease patients.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is a leading cause of hospitalizations. Interventional studies focusing on the hospital-to-home transition for COPD patients are few. In the BREATHE (Better Respiratory Education and Treatment Help Empower) study, we developed and tested a patient and family-centered transitional care program that helps prepare hospitalized COPD patients and their family caregivers to manage COPD at home. METHODS: In the study's initial phase, we co-developed the BREATHE transitional care program with COPD patients, family-caregivers, and stakeholders. The program offers tailored services to address individual patients' needs and priorities at the hospital and for 3months post discharge. We tested the program in a single-blinded RCT with 240 COPD patients who were randomized to receive the program or 'usual care'. Program participants were offered the opportunity to invite a family caregiver, if available, to enroll with them into the study. The primary outcomes were the combined number of COPD-related hospitalizations and Emergency Department (ED) visits per participant at 6months post discharge, and the change in health-related quality of life over the 6months study period. Other measures include 'all cause' hospitalizations and ED visits; patient activation; self-efficacy; and, self-care behaviors. DISCUSSION: Unlike 1month transitional care programs that focus on patients' post-acute care needs, the BREATHE program helps hospitalized COPD patients manage the post discharge period as well as prepare them for long term self-management of COPD. If proven effective, this program may offer a timely solution for hospitals in their attempts to reduce COPD rehospitalizations.

Coordinated cell motility is regulated by a combination of LKB1 farnesylation and kinase activity.

Cell motility requires the precise coordination of cell polarization, lamellipodia formation, adhesion, and force generation. LKB1 is a multi-functional serine/threonine kinase that associates with actin at the cellular leading edge of motile cells and suppresses FAK. We sought to understand how LKB1 coordinates these multiple events by systematically dissecting LKB1 protein domain function in combination with live cell imaging and computational approaches. We show that LKB1-actin colocalization is dependent upon LKB1 farnesylation leading to RhoA-ROCK-mediated stress fiber formation, but membrane dynamics is reliant on LKB1 kinase activity. We propose that LKB1 kinase activity controls membrane dynamics through FAK since loss of LKB1 kinase activity results in morphologically defective nascent adhesion sites. In contrast, defective farnesylation mislocalizes nascent adhesion sites, suggesting that LKB1 farnesylation serves as a targeting mechanism for properly localizing adhesion sites during cell motility. Together, we propose a model where coordination of LKB1 farnesylation and kinase activity serve as a multi-step mechanism to coordinate cell motility during migration.

Micrometastases and isolated tumour cells in sentinel lymph nodes in oral and oropharyngeal squamous cell carcinoma.

BACKGROUND: The occurrence of micrometastases (MMs) and isolated tumour cells (ITCs) in oral sentinel lymph node (SLN) biopsy is poorly known, and the definitions and clinical significance of MMs and ITCs in SLN biopsy are controversial. We compared the UICC/TNM definitions of MMs and ITCs with our previously published sentinel node protocol to assess how the adoption of the UICC/TNM criteria would affect the staging of nodal micrometastatic disease. METHODS: Of 107 patients who had a SLN biopsy and pathology at 150 microm intervals, 35 with metastatic tumour were included. Eighty-six SLNs were reassessed using the UICC/TNM definitions for MMs and ITCs. Findings were linked to the final pathology in the subsequent neck dissection. RESULTS: Initial H&E sections showed metastases in 24 patients (in 34 out of 61 SLN), 8 of whom (9 SLNs) had MMs. Additional step serial sections revealed metastatic deposits in a further 11 patients (15 out of 25 SLNs were positive) which were reassessed as MMs (6 patients) or ITCs (5 patients). Subsequent neck dissection revealed additional metastases in 46% of patients with MM, whilst one of the ITC patients had subsequent neck metastases (20%). CONCLUSION: Despite some limitations, the UICC/TNM classification provides an objective, uniform method of detecting MMs and ITC's. Unlike in cases with ITC, metastases in other non-SLNs were common when a micrometastasis was detected in a SLN, indicating need for further treatment of the neck.

The contribution of sociodemographic, medical, and attitudinal factors to blood donation among the general public.

BACKGROUND: Few studies have simultaneously assessed the relative importance of sociodemographic, medical, and attitudinal factors in explaining which individuals are more likely to donate blood. STUDY DESIGN AND METHODS: A cross-sectional telephone survey of households in Maryland was conducted to identify the relation of sociodemographic, medical, and attitudinal factors to blood donation history among the general public. Random digit dialing was used to identify households; individuals aged 18 to 75 years were randomly selected within households. In multivariate analyses, the independent relationship of these factors with prior history of blood donation was assessed, and the amount of variation in prior history of blood donation among the study population that could be explained by these factors was determined. RESULTS: Of 385 participants (84% of randomized homes), 228 (59%) had donated blood at least once in the past. After adjusting for potential confounders, women, black participants, and those agreeing with the statement "I am afraid of hospitals" had 60 to 80 percent lower odds of prior donation when compared with men, white participants, and those who did not agree with the statement (OR [95% CI]: 0.2 [0.1-0.4], 0.4 [0.2-0.8], and 0.3 [0.2-0.6], respectively). The effect of fear of hospitals was consistent across sex and race. Trust, fear, and suspicion of hospitals were among factors contributing most to variation in prior donation history. CONCLUSION: Female sex, black race, and fear of hospitals are three major factors negatively associated with prior history of blood donation. Fear of hospitals affects blood donation patterns across race and sex groups. Future study is needed to determine whether recruitment of blood donors may be more efficient if focused toward women, minorities, and donors' fears of healthcare facilities or hospitals.

The influence of task requirements on priming in object decision and matching.

We argue that task requirements can be the determinant in generating different results in studies on visual object recognition. We investigated priming for novel visual objects in three implicit memory tasks. A study-test design was employed in which participants first viewed line drawings of unfamiliar objects and later made different decisions about structural aspects of the objects. Priming for both symmetric and asymmetric possible objects was observed in a task requiring a judgment of structural possibility. However, when the task was changed to one requiring a judgment of structural symmetry, only symmetric possible objects showed priming. Finally, in a matching task in which participants made a same-different judgment, only symmetric possible objects exhibited priming. These results suggest that an understanding of object representation will be most fruitful if it is based on careful analyses of both the task demands and their interaction(s) with encoding and retrieval processes.

Patient perspectives on spirituality and the patient-physician relationship.

OBJECTIVE: To identify the preferences and concerns of seriously ill patients about discussing religious and spiritual beliefs with physicians. DESIGN: Three focus group discussions with patients who had experienced a recent life-threatening illness. Discussions were audiotaped, transcribed verbatim, and reviewed independently by two investigators to identify discrete comments for grouping into domains. A third investigator adjudicated differences in opinion. Comments were then independently reviewed for relevance and consistency by a health services researcher and a pastoral counselor. SETTING: Academic medical center. PARTICIPANTS: Referred sample of 22 patients hospitalized with a recent life-threatening illness. MEASUREMENTS AND MAIN RESULTS: Almost all of the 562 comments could be grouped into one of five broad domains: 1) religiosity/spirituality, 2) prayer, 3) patient-physician relationship, 4) religious/spiritual conversations, and 5) recommendations to physicians. God, prayer, and spiritual beliefs were often mentioned as sources of comfort, support, and healing. All participants stressed the importance of physician empathy. Willingness to participate in spiritual discussions with doctors was closely tied to the patient-physician relationship. Although divided on the proper context, patients agreed that physicians must have strong interpersonal skills for discussions to be fruitful. Physician-initiated conversation without a strong patient-physician relationship was viewed as inappropriate and as implying a poor prognosis. CONCLUSION: Religion and spirituality are a source of comfort for many patients. Although not necessarily expecting physicians to discuss spirituality, patients want physicians to ask about coping and support mechanisms. This exploratory study suggests that if patients then disclose the importance of spiritual beliefs in their lives, they would like physicians to respect these values.

How important is intrinsic spirituality in depression care? A comparison of white and African-American primary care patients.

We used a cross-sectional survey to compare the views of African-American and white adult primary care patients (N = 76) regarding the importance of various aspects of depression care. Patients were asked to rate the importance of 126 aspects of depression care (derived from attitudinal domains identified in focus groups) on a 5-point Likert scale. The 30 most important items came from 9 domains: 1) health professionals' interpersonal skills, 2) primary care provider recognition of depression, 3) treatment effectiveness, 4) treatment problems, 5) patient understanding about treatment, 6) intrinsic spirituality, 7) financial access, 8) life experiences, and 9) social support. African-American and white patients rated most aspects of depression care as similarly important, except that the odds of rating spirituality as extremely important for depression care were 3 times higher for African Americans than the odds for whites.

Differential evolution of eastern equine encephalitis virus populations in response to host cell type.

Arthropod-borne viruses (arboviruses) cycle between hosts in two widely separated taxonomic groups, vertebrate amplifying hosts and invertebrate vectors, both of which may separately or in concert shape the course of arbovirus evolution. To elucidate the selective pressures associated with virus replication within each portion of this two-host life cycle, the effects of host type on the growth characteristics of the New World alphavirus, eastern equine encephalitis (EEE) virus, were investigated. Multiple lineages of an ancestral EEE virus stock were repeatedly transferred through either mosquito or avian cells or in alternating passages between these two cell types. When assayed in both cell types, derived single host lineages exhibited significant differences in infectivity, growth pattern, plaque morphology, and total virus yield, demonstrating that this virus is capable of host-specific evolution. Virus lineages grown in alternation between the two cell types expressed intermediate phenotypes consistent with dual adaptation to both cellular environments. Both insect-adapted and alternated lineages greatly increased in their ability to infect insect cells. These results indicate that different selective pressures exist for virus replication within each portion of the two-host life cycle, and that alternation of hosts selects for virus populations well adapted for replication in both host systems.

Screening the public for depression through the Internet.

OBJECTIVE: Despite increased public screening, many individuals with depression remain undetected or untreated. This study explored the performance of an Internet-based program in screening for depression. METHODS: The Centers for Epidemiological Studies Depression (CES-D) scale was adapted as an online screening test. The program advised persons whose score indicated a high probability of depression to seek treatment and asked them to complete a survey of attitudes and preferences that could be printed and taken to a health professional. Responses were collected anonymously for epidemiologic research. Demographic characteristics of participants were compared with those of the U.S. population and participants in previous community screenings. The costs of the program were calculated. RESULTS: The CES-D scale was completed 24,479 times during the eight-month study period. The respondents' median age category was 30 to 45 years, and almost 30 percent were male; 58 percent (N=14,185) screened positive for depression, and fewer than half of those had never been treated for depression. The proportion of younger individuals was larger than in previous public screenings, but was still lower than that in the U.S. population. Our sample contained a lower proportion of minorities than the U.S. population (16.6 percent versus 28.3 percent). Sunk costs totaled $9,000, and additional marginal costs to maintain the system totaled $3,750. CONCLUSIONS: The Internet provides a continuously available, inexpensive, easily maintained platform to anonymously screen a large number of individuals from a broad geographic area. However, older adults and minorities may visit screening sites less frequently than other populations.

Effects of initial dose on eastern equine encephalomyelitis virus dependent mortality in intrathoracically inoculated Culiseta melanura (Diptera: Culicidae).

Viral growth characteristics that favor rapid and prodigious virion production may increase virus transmission but be detrimental to infected hosts. Several arboviruses, including eastern equine encephalomyelitis (EEE) virus, negatively affect the survival of their infected mosquito vectors. To test the hypothesis that the mosquito virulent properties of EEE virus are caused by the presence of intrinsic viral growth properties, we investigated the effects of infecting dose on the survival of intrathoracically inoculated Culiseta melanura (Coquillett). Daily survival of age-matched females inoculated with either a low initial dose of 10(1.5) plaque-forming units (PFUs) per mosquito or a high initial dose of 10(5.5) PFUs per mosquito was monitored for 8 wk. Compared with diluent inoculated controls, mosquitoes from both dosage groups displayed highly significant decreases in survival. No significant differences in daily survival were detected between the two infected groups. Virus production within inoculated mosquitoes was assessed by sampling mosquitoes every 12 h for 96 h after inoculation. Rapid virus amplification occurred in both dosage groups, and by 24 h after exposure the mean viral loads in mosquitoes inoculated with the low dose were comparable to those inoculated with the high dose. Likewise, although detectable virions appeared sooner in the saliva of high dosage mosquitoes, by 72 h after inoculation no significant differences in virus transmission were detected between the two exposure groups. These results indicate that the virulence of EEE virus for its enzootic North American mosquito vector is not dosage dependent and likely reflects the inherent growth properties of this virus within infected mosquitoes.

Analysis of FAK-associated signaling pathways in the regulation of cell cycle progression.

Focal adhesion kinase (FAK) is an important mediator of signal transduction pathways initiated by integrins in cell migration, survival and cell cycle regulation. The ability of FAK to mediate integrin signaling in the regulation of cell cycle progression depends on the phosphorylation of Tyr397, which implies a functional significance for the formation of FAK signaling complexes with Src, phosphatidylinositol-3-kinase (PI3K) and Grb7. We have previously described a FAK mutant, D395A, that selectively disrupts FAK binding to PI3K, but allows FAK association with Src. Using this mutation in a mislocalized FAK mutant background, we show here that formation of a FAK/PI3K complex is not sufficient for cell cycle progression but the formation of a FAK/Src complex plays an essential role. We also show that mutation of D395 to A disrupted FAK association with Grb7. This suggests that a FAK/Grb7 complex is not involved in the cell cycle regulation either, which is supported by direct analysis of cells expressing a dominant negative Grb7 construct. Finally, we provide evidence that the Src-dependent association of FAK with Grb2 and p130(Cas) are both required for the regulation of cell cycle progression by FAK. Together, these studies identify important FAK downstream signaling pathways in cell cycle regulation.

Genetic characterization of H3N2 influenza viruses isolated from pigs in North America, 1977-1999: evidence for wholly human and reassortant virus genotypes.

Since 1998, H3N2 viruses have caused epizootics of respiratory disease in pigs throughout the major swine production regions of the U.S. These outbreaks are remarkable because swine influenza in North America had previously been caused almost exclusively by H1N1 viruses. We sequenced the full-length protein coding regions of all eight RNA segments from four H3N2 viruses that we isolated from pigs in the Midwestern U.S. between March 1998 and March 1999, as well as from H3N2 viruses recovered from a piglet in Canada in January 1997 and from a pig in Colorado in 1977. Phylogenetic analyses demonstrated that the 1977 Colorado and 1997 Ontario isolates are wholly human influenza viruses. However, the viruses isolated since 1998 from pigs in the Midwestern U.S. are reassortant viruses containing hemagglutinin, neuraminidase and PB1 polymerase genes from human influenza viruses, matrix, non-structural and nucleoprotein genes from classical swine viruses, and PA and PB2 polymerase genes from avian viruses. The HA proteins of the Midwestern reassortant swine viruses can be differentiated from those of the 1995 lineage of human H3 viruses by 12 amino acid mutations in HA1. In contrast, the Sw/ONT/97 virus, which did not spread from pig-to-pig, lacks 11 of these changes.

Primary care patients' opinions regarding the importance of various aspects of care for depression.

The objectives of this study were to 1) ascertain the importance of various aspects of depression care from the patient's perspective and 2) select items and scales for inclusion in a new instrument to measure primary care patients' attitudes toward and ratings of depression care. We used a cross-sectional survey at a university-based urban primary care clinic; the subjects were adult patients being recruited for a study of minor depression. To help prioritize attitudinal domains, including 126 items identified previously in focus groups, we asked patients to rate the importance of each aspect of depression care on a five-point scale. Items were ranked according to mean scores and the percentage of patients ranking the items as extremely important. The items were selected for inclusion in an instrument to measure patients' attitudes toward depression care based on their importance ratings. We performed reliability and validity testing of scales comprising the 30 most important items and a shortened version that includes 16 items. The sample included 76 patients (mean age 34.8 years; mean CES-D score, 22.2; 72% women; 36% African-American; 32% college graduates). Forty-six percent had visited a mental health professional in the past. The top 30 items for the overall sample came from the following domains: 1) health care providers' interpersonal skills, 2) primary care provider recognition of depression, 3) treatment effectiveness, 4) treatment problems, 5) patient understanding about treatment, 6) intrinsic spirituality, and 7) financial access to services. Scales comprising items from these domains show adequate internal consistency (Cronbach's alpha >0.70) as well as convergent and discriminant validity. We have designed a brief patient-centered instrument for measuring attitudes toward depression care that has evidence for internal item consistency reliability and discriminant validity.

A simple restriction fragment length polymorphism-based strategy that can distinguish the internal genes of human H1N1, H3N2, and H5N1 influenza A viruses.

A simple molecular technique for rapid genotyping was developed to monitor the internal gene composition of currently circulating influenza A viruses. Sequence information from recent H1N1, H3N2, and H5N1 human virus isolates was used to identify conserved regions within each internal gene, and gene-specific PCR primers capable of amplifying all three virus subtypes were designed. Subtyping was based on subtype-specific restriction fragment length polymorphism (RFLP) patterns within the amplified regions. The strategy was tested in a blinded fashion using 10 control viruses of each subtype (total, 30) and was found to be very effective. Once standardized, the genotyping method was used to identify the origin of the internal genes of 51 influenza A viruses isolated from humans in Hong Kong during and immediately following the 1997-1998 H5N1 outbreak. No avian-human or H1-H3 reassortants were detected. Less than 2% (6 of 486) of the RFLP analyses were inconclusive; all were due to point mutations within a restriction site. The technique was also used to characterize the internal genes of two avian H9N2 viruses isolated from children in Hong Kong during 1999.

Evidence for unconscious memory processing during elective cardiac surgery.

BACKGROUND: Many anesthetic drugs have been shown to disrupt conscious recall (explicit memory) in volunteers. However, unconscious processing (implicit memory) of intraoperative auditory material may occur during general anesthesia and may provide an opportunity for intraoperative therapeutic intervention. In this study, we examined patients undergoing elective cardiac surgery for evidence of intraoperative implicit and explicit memory. METHODS AND RESULTS: Twenty-five subjects provided written informed consent and underwent general anesthesia and cardiopulmonary bypass for cardiac surgery. During the operation, patients were randomized to receive 1 of 2 different audiotapes of associated word pairs. Postoperatively, a blinded observer conducted a standardized interview to determine the extent of intraoperative implicit and explicit memory. With the use of free association, significant intraoperative implicit memory was found. In contrast, no patient had spontaneous or directed recall of intraoperative events, and we did not find evidence of intraoperative explicit memory with a recognition task. CONCLUSIONS: Patients undergoing general anesthesia for cardiac surgery were reliably able to reinforce associations between word pairs solely on the basis of their intraoperative presentation. This provides further evidence that patients are capable of processing intraoperative auditory information.

Direction of motion influences perceptual identification of ambiguous figures.

It is known that the perceived identity of an ambiguous figure can influence how that figure is perceived to move. In 6 experiments, the converse effect-the role of motion in the perceptual identification of ambiguous figures (e.g., N. Tinbergen's, 1951, goose-hawk)-was examined. In general, observers were biased to identify a moving ambiguous figure as that object whose face pointed in the direction of motion. Experiments 1-4 replicated this basic effect over induced, apparent, and smooth motion displays. Results from Experiment 5 show that longer interstimulus intervals led to smaller biases, with all bias disappearing around 1,500 ms. In Experiment 6, direction of motion influenced perceptual identification even in the presence of conflicting shape information.

Vector competence of mosquitoes (Diptera:Culicidae) from Massachusetts for a sympatric isolate of eastern equine encephalomyelitis virus.

We tested susceptibility to per os infection and potential salivary transmission for eastern equine encephalomyelitis (EEE) virus in Aedes canadensis (Theobald), Aedes vexans (Meigen), Anopheles quadrimaculatus (Say), Anopheles punctipennis (Say), Coquillettidia perturbans (Walker), and Culex salinarius (Coquillett). Culiseta melanura (Coquillett), the documented enzootic vector of EEE virus, was our control. Based on these estimates of laboratory vector competence and other behavioral and ecological components of vectorial capacity, we ranked these 6 species from the most to least probable epidemic vectors: Cx. salinarius, An. quadrimaculatus, Ae. canadensis, Cq. perturbans, Ae. vexans, and An. punctipennis.

Effects of size and orientation change on hippocampal activation during episodic recognition: a PET study.

To determine whether physical match between studied and tested items influences blood flow increases in the hippocampal formation associated with recognition memory, positron emission tomography (PET) was used to measure changes in regional cerebral blood flow while healthy volunteers made old/new judgements about line drawings of objects. Some objects were tested in the same size and orientation as they had appeared earlier during the study phase of the experiment; other objects were tested in a different size or orientation than when they were studied. Blood flow increases in the vicinity of the hippocampal formation were observed in the same object condition compared with the size change and the orientation change conditions, even though recognition accuracy was affected significantly only by orientation change. Results add to previous findings suggesting that physical similarity between studied items and test cues may contribute to hippocampal activation during episodic retrieval.

Neuroanatomical correlates of implicit and explicit memory for structurally possible and impossible visual objects.

Implicit memory refers to nonconscious retrieval of past experience demonstrated by facilitation in test performance on tasks that do not require intentional recollection of previous experiences. Explicit memory, in contrast, refers to the conscious retrieval of prior information, as demonstrated during standard recall and recognition tasks. In this experiment, positron emission tomographic (PET) measurements of regional cerebral blood flow (CBF), a marker of local neuronal activity, were used to identify and contrast brain regions that participate in the perception, implicit memory, and explicit memory for structurally possible and impossible visual objects. Ten CBF images were acquired in 16 normal women as they made possible/impossible and old/new recognition decisions about previously studied (old) and nonstudied (new) structurally possible and impossible objects. As reported previously, object decisions for familiar possible objects were associated with increased CBF in the vicinity of the left inferior temporal and fusiform gyri and recognition memory for familiar possible objects was associated with increased CBF in the vicinity of the right hippocampus. In this report, we provide more extensive analyses of the roles of the inferior temporal cortex, the hippocampus, the parahippocampus, and the pulvinar in encoding and retrieval operations. Additionally, patterns of CBF increases and decreases provide information regarding the neural structures involved in implicit and explicit memory.