Subcutaneous cladribine to treat multiple sclerosis: experience in 208 patients.

OBJECTIVE: To report on safety and effectiveness of subcutaneous cladribine (Litak®) in multiple sclerosis (MS) patients. METHODS: Litak® was offered to MS-patients irrespective of disease course. Litak® 10 mg was administered for 3-4 days during week 1. Based on lymphocyte count at week 4, patients received another 0-3 doses at week 5. A second course was administered 11 months later. Follow-up included adverse events, relapses, expanded disability status scale (EDSS), 9-hole-peg and Timed-25-foot-walking tests, no-evidence-of-disease-activity (NEDA), no-evidence-of-progression-or-active-disease (NEPAD), MRI, cerebrospinal fluid (CSF) neurofilament light chain (NfL), and lymphocyte counts. RESULTS: In all, 208 patients received at least one course of treatment. Age at baseline was 44 (17-72) years and EDSS 0-8.5. Cladribine was generally well tolerated. One myocardial infarction, one breast cancer, and three severe skin reactions occurred without long-term sequelae. Two patients died (one pneumonia, one encephalitis). Lymphopenia grade 3 occurred in 5% and grade 4 in 0.5%. In 94 out of 116 pwMS with baseline and follow-up (BaFU) data after two treatment courses, EDSS remained stable or improved. At 18 months, 64% of patients with relapsing MS and BaFU data (n = 39) had NEDA. At 19 months, 62% of patients with progressive MS and BaFU data (n = 13) had NEPAD. Of n = 13 patients whose CSF-NfL at baseline was elevated, 77% were normalised within 12 months. CONCLUSIONS: Litak® was well tolerated. Effectiveness in relapsing MS appeared similar to cladribine tablets and was encouraging in progressive MS. Our data suggest cladribine may be safe and effective in MS-patients irrespective of their disease stage.

Identification and characterization of Photorhabdus temperata mutants altered in hemolysis and virulence.

Photorhabdus temperata is a symbiont of the entomopathogenic nematode Heterorhabditis bacteriophora and an insect pathogen. This bacterium produces a wide variety of virulence factors and hemolytic activity. The goal of this study was to identify hemolysin-defective mutants and test their virulence. A genetic approach was used to identify mutants with altered hemolytic activity by screening a library of 10 000 P. temperata transposon mutants. Three classes of mutants were identified: (i) defective (no hemolytic activity), (ii) delayed (delayed initiation of hemolytic activity), and (iii) early (early initiation of hemolytic activity). The transposon insertion sites for these mutants were identified and used to investigate other physiological properties, including insect pathogenesis and motility. The hemolysin-defective mutants, P10A-C11, P10A-H12, and P79-B5, had inserts in genes involved in RNA turnover (RNase II and 5'-pentaphospho-5'-adenosine pyrophosphohydrolase) and showed reduced virulence and production of extracellular factors. These data support the role of RNA turnover in insect pathogenesis and other physiological functions.

The effect of occlusion therapy on motion perception deficits in amblyopia.

There is growing evidence for deficits in motion perception in amblyopia, but these are rarely assessed clinically. In this prospective study we examined the effect of occlusion therapy on motion-defined form perception and multiple-object tracking. Participants included children (3-10years old) with unilateral anisometropic and/or strabismic amblyopia who were currently undergoing occlusion therapy and age-matched control children with normal vision. At the start of the study, deficits in motion-defined form perception were present in at least one eye in 69% of the children with amblyopia. These deficits were still present at the end of the study in 55% of the amblyopia group. For multiple-object tracking, deficits were present initially in 64% and finally in 55% of the children with amblyopia, even after completion of occlusion therapy. Many of these deficits persisted in spite of an improvement in amblyopic eye visual acuity in response to occlusion therapy. The prevalence of motion perception deficits in amblyopia as well as their resistance to occlusion therapy, support the need for new approaches to amblyopia treatment.

Quadruple quorum-sensing inputs control Vibrio cholerae virulence and maintain system robustness.

Bacteria use quorum sensing (QS) for cell-cell communication to carry out group behaviors. This intercellular signaling process relies on cell density-dependent production and detection of chemical signals called autoinducers (AIs). Vibrio cholerae, the causative agent of cholera, detects two AIs, CAI-1 and AI-2, with two histidine kinases, CqsS and LuxQ, respectively, to control biofilm formation and virulence factor production. At low cell density, these two signal receptors function in parallel to activate the key regulator LuxO, which is essential for virulence of this pathogen. At high cell density, binding of AIs to their respective receptors leads to deactivation of LuxO and repression of virulence factor production. However, mutants lacking CqsS and LuxQ maintain a normal LuxO activation level and remain virulent, suggesting that LuxO is activated by additional, unidentified signaling pathways. Here we show that two other histidine kinases, CqsR (formerly known as VC1831) and VpsS, act upstream in the central QS circuit of V. cholerae to activate LuxO. V. cholerae strains expressing any one of these four receptors are QS proficient and capable of colonizing animal hosts. In contrast, mutants lacking all four receptors are phenotypically identical to LuxO-defective mutants. Importantly, these four functionally redundant receptors act together to prevent premature induction of a QS response caused by signal perturbations. We suggest that the V. cholerae QS circuit is composed of quadruple sensory inputs and has evolved to be refractory to sporadic AI level perturbations.

Cognitive processing of visual images in migraine populations in between headache attacks.

BACKGROUND AND OBJECTIVE: People with migraine headache have altered interictal visual sensory-level processing in between headache attacks. Here we examined the extent to which these migraine abnormalities may extend into higher visual processing such as implicit evaluative analysis of visual images in between migraine events. METHODS: Specifically, we asked two groups of participants--migraineurs (N=29) and non-migraine controls (N=29)--to view a set of unfamiliar commercial logos in the context of a target identification task as the brain electrical responses to these objects were recorded via event-related potentials (ERPs). Following this task, participants individually identified those logos that they most liked or disliked. We applied a between-groups comparison of how ERP responses to logos varied as a function of hedonic evaluation. RESULTS: Our results suggest migraineurs have abnormal implicit evaluative processing of visual stimuli. Specifically, migraineurs lacked a bias for disliked logos found in control subjects, as measured via a late positive potential (LPP) ERP component. CONCLUSIONS: These results suggest post-sensory consequences of migraine in between headache events, specifically abnormal cognitive evaluative processing with a lack of normal categorical hedonic evaluation.

Interictal neurocognitive processing of visual stimuli in migraine: evidence from event-related potentials.

Research has established decreased sensory habituation as a defining feature in migraine, while decreased cognitive habituation has only been found with regard to cognitive assessment of the relative probability of the occurrence of a stimulus event. Our study extended the investigation of interictal habituation in migraine to include cognitive processing when viewing of a series of visually-complex images, similar to those we encounter on the internet everyday. We examined interictal neurocognitive function in migraine from a habituation perspective, using a novel paradigm designed to assess how the response to a series of images changes over time. Two groups of participants--migraineurs (N = 25) and non-migraine controls (N = 25)--were asked to view a set of 232 unfamiliar logos in the context of a target identification task as their brain electrical responses were recorded via event-related potentials (ERPs). The set of logos was viewed serially in each of 10 separate trial blocks, with data analysis focusing on how the ERP responses to the logos in frontal electrodes from 200-600 ms changed across time within each group. For the controls, we found that the amplitude of the late positive potential (LPP) ERP component elicited by the logos had no significant change across trial blocks. In contrast, in migraineurs we found that the LPP significantly increased in amplitude across trial blocks, an effect consistent with a lack of habituation to visual stimuli seen in previous research. Our findings provide empirical support abnormal cognitive processing of complex visual images across time in migraineurs that goes beyond the sensory-level habituation found in previous research.

Older adults' fears about diabetes: using common sense models of disease to understand fear origins and implications for self-management.

This study examines older adults' fears of diabetes complications and their effects on self-management practices. Existing models of diabetes self-management posit that patients' actions are grounded in disease beliefs and experience, but there is little supporting evidence. In-depth qualitative interviews were conducted with a community-based sample of 74 African American, American Indian, and white older adults with diabetes. Analysis uses Leventhal's Common Sense Model of Diabetes to link fears to early experience and current self-management. Sixty-three identified fears focused on complications that could limit carrying out normal activities: amputation, blindness, low blood glucose and coma, and disease progression to insulin use and dialysis. Most focused self-management on actions to prevent specific complications, rather than on managing the disease as a whole. Early experiences focused attention on the inevitability of complications and the limited ability of patients to prevent them. Addressing older adults' fears about diabetes may improve their diabetes self-management practices.

Contraception and clean needles: feasibility of combining mobile reproductive health and needle exchange services for female exotic dancers.

Young women engaged in exotic dancing have a higher need for reproductive health services than women not in this profession, and many also use drugs or exchange sex for money or drugs. Few report receiving reproductive health services. We describe a public health, academic, and community partnership that provided reproductive health services on needle exchange mobile vans in the "red light district" in downtown Baltimore, Maryland. Women made 220 visits to the vans in the first 21 months of the program's operation, and 65% of these visits involved provision of contraception. Programmatic costs were feasible. Joint provision of needle exchange and reproductive health services targeting exotic dancers has the potential to reduce unintended pregnancies and link pregnant, substance-abusing women to reproductive care, and such programs should be implemented more widely.

Reflexive attentional orienting in migraineurs: The behavioral implications of hyperexcitable visual cortex.

INTRODUCTION: Although migraine is classified as a headache disorder, a key part of migraine pathophysiology is a heightened excitability of visual cortices in between headache events. The goal of our study was to examine the behavioral impact of this visuocortical hyperexcitability, in terms of its effect on reflexive visual attentional orienting. METHODS AND RESULTS: In Experiment 1, using a non-predictive spatial cuing task that relied on sensory-evoked responses in the visual cortex for triggering attentional orienting, we found that migraineurs had greater attentional enhancement of manual target responses, relative to non-migraine controls. In two control experiments we confirmed that this heightened attention effect in migraineurs is not due to exaggerated reflexive orienting responses in general, but rather, it appears to be specifically associated with sensory-evoked attentional triggers. DISCUSSION: Taken together, this confirms that the functional consequences of hyperexcitable visual cortex in migraineurs are not just purely sensory in nature, but directly impact at least some forms of reflexive attention. This provides evidence of at least one cognitive implication of hyperexcitable visual cortical responses in migraineurs, namely heightened reflexive visual-spatial orienting specific to sudden-onset peripheral events.

Older adults' common sense models of diabetes.

OBJECTIVE: To investigate the importance of viewing belief systems about health maintenance holistically. METHODS: Qualitative (N=74) and quantitative data (N=95) were obtained from a multi-ethnic rural-dwelling sample of older adults with diabetes to characterize their common sense models (CSMs) of diabetes. RESULTS: There is a discrete number of CSMs held by older adults, each characterized by unique clusters of diabetes-related knowledge and beliefs. Individuals whose CSM was shaped by biomedical knowledge were better able to achieve glycemic control. CONCLUSIONS: Viewing individuals' health beliefs incrementally or in a piece-meal strategy may be less effective for health behavior change than focusing on beliefs holistically.

Blood glucose symptom recognition: perspectives of older rural adults.

PURPOSE: Blood glucose symptom recognition and the interpretation of how one feels with regard to low or high glucose can impact how diabetes is self-managed. Understanding interpretation of symptoms related to diabetes and ultimate glucose regulation can be challenging. Health care providers can develop strategies to improve care by listening to individuals describe their symptoms in the context of everyday life. METHODS: The perspectives of older rural adults were assessed through individual in-depth interviews conducted among 75 African American, American Indian, and white individuals. The study design included a sample balanced with regard to sex, ethnicity, and educational attainment. The Self-Regulatory Model of Illness and the concept that people construct their own common sense models of health were utilized in this study. RESULTS: There were four dominant themes of symptoms described that were related to blood glucose. These categories included sensations, lightheadedness, energy level, and eyesight changes. Participants described symptoms they experienced at perceived levels of both high and low blood glucose. Results suggest that older adults were unable to distinguish whether their symptoms occurred because of high or low blood glucose. CONCLUSION: Education that incorporates methods to aid older individuals differentiate blood glucose levels related to diabetes symptoms could help improve self-management.

Calling the doctor: a qualitative study of patient-initiated physician consultation among rural older adults.

OBJECTIVE: Guided by Leventhal's self-regulatory model and Cockerham's theory of health lifestyles, we explore two questions regarding physician consultation among elderly rural adults: What symptom characteristics prompt patient-initiated physician consultation? Do participants' accounts of responses to symptoms, including the decision to consult a physician, incorporate descriptions of change over time? METHOD: We analyze data from semistructured in-depth interviews with 62 older rural adults. RESULTS: Accounts of decisions to initiate contact with physicians support prior research. Some symptoms encouraged immediate consultation; others prompted periods of monitoring and lay management. Physicians were most often contacted if changes were new, unusually severe, persisted or worsened, or failed to respond to lay treatment. DISCUSSION: We characterize participants' responses to symptoms as bricolages to highlight their construction from available materials. Incorporating the integrating concept of bricolage and Cockerham's emphasis on both general dispositions and symptom-specific responses represents an important extension of Leventhal's conceptualization of illness behavior, including patient-initiated physician consultation.

Development and pilot testing of the collaborative practice assessment tool.

Collaborative practice is receiving increased attention as a model of healthcare delivery that positively influences the effectiveness and efficiency of patient care while improving the work environment of healthcare providers. The collaborative practice assessment tool (CPAT) was developed from the literature to enable interprofessional teams to assess their collaborative practice. The CPAT survey included 56 items across nine domains including: mission and goals; relationships; leadership; role responsibilities and autonomy; communication; decision-making and conflict management; community linkages and coordination; perceived effectiveness and patient involvement; in addition to three open-ended questions. The tool was developed for use in a variety of settings involving a diversity of healthcare providers with the aim of helping teams to identify professional development needs and corresponding educational interventions. The results of two pilot tests indicated that the CPAT is a valid and reliable tool for assessing levels of collaborative practice within teams. This article describes the development of the tool, the pilot testing and validation process, as well as limitations of the tool.

Linking glycemic control and executive function in rural older adults with diabetes mellitus.

OBJECTIVES: To examine the association between glycemic control and the executive functioning domain of cognition and to identify risk factors for inadequate glycemic control that may explain this relationship. DESIGN: Cross-sectional study. SETTING: In-person interviews conducted in participants' homes. PARTICIPANTS: Ninety-five rural older African Americans, American Indians, and whites with diabetes mellitus (DM) from three counties in south-central North Carolina. MEASUREMENTS: Participants underwent uniform evaluations. Glycemic control was measured using a validated method, and executive function was assessed using a previously established set of measures and scoring procedure. Information pertaining to medication for treatment of DM, knowledge of DM, and DM self-care behaviors were obtained. RESULTS: In linear regression models adjusting for sex, age, education, ethnicity, duration of DM, and depressive symptoms, executive function was significantly associated with glycemic control. A 1-point higher executive function score was associated with a 0.47 lower glycosylated hemoglobin value (P=.01). The association between glycemic control and executive function became nonsignificant (P=.08) when controlling for several glycemic control risk factors, including use of DM medication and DM knowledge. CONCLUSION: These results suggest that poor glycemic control is associated with impairments in performance on composite measures of executive function and that modifiable risk factors for glycemic control such as use of DM medication and DM knowledge may explain this relationship.

Utilization patterns and correlates of retention among clients of the needle exchange program in Baltimore, Maryland.

NEP effectiveness at a population level depends on several factors, including the number of injection drug users (IDUs) retained, or consistently accessing services. Patterns of retention in the Baltimore Needle Exchange Program (BNEP) from 1994 to 2006 were calculated using enrollment surveys and client records. We used Andersen's Behavioral Model of Health Services Use to frame our examination of factors associated with retention. Client retention was measured in two ways: whether a client returned to the exchange within 12 months of enrollment and how many times a client returned within these 12 months. BNEP clients (N=12,388) were predominantly male (69%), African-American (73%), and >or=age 30 (86%). Nearly two-thirds (64%) of clients returned within 12 months of their first BNEP visit. The median number of return visits per client within 12 months was one (IQR: 0-5). Young age (<30), being married, having an injection drug use history of less than 20 years, and living farther from the BNEP site were characteristics independently associated with both measures of low retention in multivariate analysis. Among younger injectors, geographical proximity was a particularly important predictor of retention. Further insight into the influence of these factors may help in developing programmatic changes that will be effective in increasing retention.

Complementary therapy use and health self-management among rural older adults.

OBJECTIVES: This article describes dimensions of complementary therapy use among rural older adults, employs these dimensions to delineate sets of complementary therapy use, and describes the personal characteristics related to each set of complementary therapy use. METHODS: Data are from in-depth interviews conducted with 62 African American and White rural older adults. RESULTS: Three dimensions of complementary therapy use are delineated: types of therapies used, mindfulness in therapy use, and sharing information with conventional health care providers. The intersection of these dimensions indicates 5 patterned sets of complementary therapy use among rural older adults: (a) mindful use of only home remedies; (b) mindful use of home remedies and contemporary supplements; (c) mindful use of home remedies, contemporary supplements, and complementary practices; (d) nonmindful use of home remedies and contemporary supplements; and (e) use of conventional care only. Involvement in the 5 sets of therapy use is related to sex, ethnicity, educational attainment, and migration. DISCUSSION: Understanding how older adults include sets of complementary therapies in their health self-management is important for improving their health care resources, expectations, awareness, and priorities.

A new inter-professional course preparing learners for life in rural communities.

The 'Professionals in Rural Practice' course was developed with the aim of preparing students enrolled in professional programs in Canada to become better equipped for the possible eventuality of professional work in a rural setting. To match the reality of living and working in a rural community, which by nature is interprofessional, the course designers were an interprofessional teaching team. In order to promote group cohesiveness the course included the participation of an interprofessional group of students and instructors from the disciplines of medicine, nursing, occupational therapy, physical therapy, teacher education, and theology. The format of the course included three-hour classes over an eight-week period and a two-day field experience in a rural community. The course utilized various experiential and interactive teaching and learning methods, along with a variety of assessment methods. Data were collected from student participants over two iterations of the course using a mixed methods approach. Results demonstrate that students value the interprofessional and experiential approach to learning and viewed this course as indispensable for gaining knowledge of other professions and preparation for rural practice. The data reveal important organizational and pedagogical considerations specific to interprofessional education, community based action research, and the unique interprofessional nature of training for life and work in a rural community. This study also indicates the potential value of further longitudinal study of participants in this course. Key words: Canada, community based action research, education, interdisciplinary, interprofessional.

Entry-level interprofessional education: perceptions of physical and occupational therapists currently practicing in Ontario.

To gain insight into the specific interprofessional education (IPE) needs of occupational and physical therapists, an online questionnaire was developed and distributed to currently practicing therapists in the province of Ontario, Canada. The questionnaire included both open- and closed-ended questions to survey the opinions, perceptions, and experiences of therapists working both in public and private practice who possess varying levels of clinical training and years of experience. Data collection resulted in 765 responses (397 OTs, 368 PTs), which allowed for a 95% confidence level based on 2007 population totals supplied by the professional colleges. Data analysis involved descriptive data analysis in conjunction with percentage comparisons of the responses as well as the coding of responses to open-ended questions. The therapists' opinions regarding the type, amount, and need for IPE were compared based on discipline and area of practice. Overall, the data show that 97% of OTs and PTs in both public and private settings hold IPE to be important for effective clinical practice. When asked about their own IPE experiences, only 50% of OTs and 43% of PTs felt that they received an appropriate level of IPE training during their entry-level clinical training. When given the choice to select the location/time when IPE should be completed, 65% choose clinical placements, with 26% classroom. Implications of the findings as well as study limitations are discussed.