A novel affective-motivational-based Overground System for detecting spinal cord injury-associated thermal and mechanical hypersensitivity in rats.

BACKGROUND: Preclinical research for neuropathic pain has depended primarily on the use of behavioural nociceptive testing that is sensory-discriminatory-based and reflexive in nature. This can be particularly problematic in spinal cord injury (SCI)-associated neuropathic pain research where hyperreflexia may develop thus confounding interpretation of reflexive responses as pain symptoms. To address this, we have designed an affective-motivational-based Overground System that has interchangeable floors to allow examination of nociceptive behaviours in response to mechanical and cold stimuli prior to and following spinal cord injury. METHODS: The animals were pretrained for 3-4 weeks to cross three Overground System surfaces (cold, rough and neutral) at a consistent pace in order to obtain a food reward (Froot Loops™ ). RESULTS: Following SCI, crossing times were significantly decreased due to more rapid crossing over the cold surface despite forgoing of the food reward, in contrast with the sham control animals. This was correlated with the development of cold hypersensitivity as assessed by standard acetone droplet testing. In response to the rough surface, slower paced crossings (increased time to cross) were observed post-SCI (also resulting in forgoing of the food reward), compared to pre-SCI times and sham control animals. This was correlated with the development of mechanical hypersensitivity as assessed by standard von Frey testing. CONCLUSIONS: Different responses in crossing behaviour for the cold and rough surfaces suggest a precise adaptive change in decision-making behaviour depending on the stimulus presented; thus, outcome measures may be easily tailored for different types of hypersensitivity symptoms. SIGNIFICANCE: We have designed an Overground System that is easy to establish and addresses a major concern in preclinical pain research by providing a cognitive- and motivational-based system for hypersensitivity detection. The affective-motivational-based Overground System allows examination of pain-like behaviours in response to cold (thermal) and rough (mechanical) stimulation prior to and following spinal cord injury. This system provides a more holistic and comprehensive assessment of nociceptive responses following SCI and helps overcome concerns of hyperreflexia confounding-evoked behavioural outcome measures in SCI models. Further, the incorporation of cognitive and motivational components brings preclinical research closer to replicating the clinical experience of a patient's motivation to participate in rewarding lifestyle activities in relation to their pain.

5-HT precursor loading, but not 5-HT receptor agonists, increases motor function after spinal cord contusion in adult rats.

Serotonergic (5-HT) receptors are upregulated following spinal cord transection. Stimulation by administration of serotonergic receptor agonists has been successful in improving hindlimb function. We tested whether this strategy would be successful in incomplete injury models (moderate or severe thoracic contusion) where descending projections are partially spared which should produce less denervation-induced receptor upregulation. Adult rats received midthoracic moderate (MOD: 25 mm drop) or severe (SEV: 50 mm drop) contusion injuries. Distribution of 5-HT and its transporter and expression of 5-HT(2C) receptors were evaluated in lumbar spinal cord and motor response to 5-HT receptor activation was assessed using open field locomotion (BBB) score, percent weight supported treadmill stepping (%WS) and evaluation of hindlimb muscle activation (tremor and serotonin syndrome). 5-HT immunostaining 3 months post-contusion revealed few 5-HT fibers caudal to the severe contusion, and more spared caudal to the moderate contusion. The distribution of 5-HT transporter paralleled 5-HT staining, but was more greatly reduced. Thus serotonin reuptake may be less efficient in the injured spinal cord. Immunostaining for the 5-HT(2C) receptor in the dorsal and ventral horns at L5 showed significant upregulation in SEV, compared to sham or MOD rats. Neither 5-HT(2C) nor 5-HT(1A) receptor agonists, alone or in combination, nor the serotonin transporter inhibitor d-fenfluramine modified BBB scores or %WS in either group. Despite the increased sensitivity of post-synaptic targets, agonist treatment did not improve function in SEV rats. We conclude that selective 5-HT(2C) or 5-HT(1A) receptor activation was not effective in improving hindlimb function after incomplete lesions. In contrast, the 5-HT precursor 5-hydroxytryptophan (L-5-HTP), which leads to activation of all classes of 5-HT receptors, increased both %WS and hindlimb activity in the MOD group. While no side effects were observed in normal or MOD rats, SEV rats displayed hindlimb tremors and 33% mortality, indicating hypersensitivity to the precursor.

The Cutaneous Assessment Tool: development and reliability in juvenile idiopathic inflammatory myopathy.

OBJECTIVES: Clinical care and therapeutic trials in idiopathic inflammatory myopathies (IIM) require accurate and consistent assessment of cutaneous involvement. The Cutaneous Assessment Tool (CAT) was designed to measure skin activity and damage in IIM. We describe the development and inter-rater reliability of the CAT, and the frequency of lesions endorsed in a large population of juvenile IIM patients. METHODS: The CAT includes 10 activity, 4 damage and 7 combined lesions. Thirty-two photographic slides depicting IIM skin lesions were assessed by 11 raters. One hundred and twenty-three children were assessed by 11 paediatric rheumatologists at 10 centres. Inter-rater reliability was assessed using simple agreements and intra-class correlation coefficients (ICC). RESULTS: Simple agreements in recognizing lesions as present or absent were generally high (0.5-1.0). ICCs for CAT lesions were moderate (0.4-0.75) in both slides and real patients. ICCs for the CAT activity and damage scores were 0.71 and 0.81, respectively. CAT activity scores ranged from 0 to 44 (median 7, potential range 0-96) and CAT damage scores ranged from 0 to 13 (median 1, potential range 0-22). The most common cutaneous lesions endorsed were periungual capillary loop changes (63%), Gottron's papules/sign (53%), heliotrope rash (49%) and malar/facial erythema (49%). CONCLUSIONS: Total CAT activity and damage scores have moderate to good reliability. Assessors generally agree on the presence of a variety of cutaneous lesions. The CAT is a promising, semi-quantitative tool to comprehensively assess skin disease activity and damage in IIM.

The impact on patient trust of legalising physician aid in dying.

OBJECTIVE: Little empirical evidence exists to support either side of the ongoing debate over whether legalising physician aid in dying would undermine patient trust. DESIGN: A random national sample of 1117 US adults were asked about their level of agreement with a statement that they would trust their doctor less if "euthanasia were legal [and] doctors were allowed to help patients die". RESULTS: There was disagreement by 58% of the participants, and agreement by only 20% that legalising euthanasia would cause them to trust their personal physician less. The remainder were neutral. These attitudes were the same in men and women, but older people and black people had more agreement that euthanasia would lower trust. However, overall, only 27% of elderly people (age 65+) and 32% of black people thought that physician aid in dying would lower trust. These views differed with physical and mental health, and also with education and income, with those having more of these attributes tending to view physician aid in dying somewhat more favourably. Again, however, overall views in most of these subgroups were positive. Views about the effect of physician aid in dying on trust were significantly correlated with participants' underlying trust in their physicians and their satisfaction with care. In a multivariate regression model, trust, satisfaction, age, and white/black race remained independently significant. CONCLUSION: Despite the widespread concern that legalising physician aid in dying would seriously threaten or undermine trust in physicians, the weight of the evidence in the USA is to the contrary, although views vary significantly.

Physiological and biomechanical responses while running with and without a stroller.

AIM: This study examined the effects of pushing a jogging stroller on biomechanical and physiological variables. The hypothesis was that running with a stroller for 30 minutes would shorten stride length and increase physiological indices of exercise. EXPERIMENTAL DESIGN: this was a repeated measures design. SETTING: participants were recruited from road races in the Dallas/Fort Worth, TX area. Graded exercise tests were performed in a laboratory setting, field tests were performed on a 400 m all-weather outdoor track. PARTICIPANTS: 5 males and 5 females were assessed. INTERVENTIONS: participants performed a graded exercise test and 2 field tests. The 1st field test involved running at 75% VO2max for 30 minutes without a stroller and the 2nd involved running at the same speed with the stroller. MEASURES: VO2, stride length, heart rate, lactate, ventilation, and RPE were evaluated. RESULTS: No differences for VO2 or stride length were evident. Heart rate (p=0.0001), lactate concentration (p=0.025), ventilation (p=0.009), and RPE (p=0.002) increased from 10 to 30 minutes while running with the stroller. Heart rate (p=0.002), lactate concentration (p=0.0001), ventilation (p=0.006), and RPE (p=0.001) were significantly higher while running with the stroller after 30 minutes compared to running without it. CONCLUSION: These results indicate that pushing a stroller affects some indices of exercise intensity while running. Gait does not change. These data do not support an association between stroller use during running and an increase risk of orthopedic injury. Further studies should examine these variables at lower intensities that are run by most recreational joggers.

Baseline experience with Modified Mini Mental State Exam: The Women's Health Initiative Memory Study (WHIMS).

The Modified Mini Mental State Exam (3MS) is widely used for screening global cognitive functioning, however little is known about its performance in clinical trials. We report the distribution of 3MS scores among women enrolled in the Women's Health Initiative Memory Study (WHIMS) and describe differences in these scores associated with age, education, and ethnicity. The 3MS exams were administered to 7,480 women aged 65-80 who had volunteered for and were eligible for a clinical trial on postmenopausal hormone therapy. General linear models were used to describe demographic differences among scores. Factor analysis was used to characterize the correlational structure of exam subscales.The distribution of 3MS scores at baseline was compressed in WHIMS compared to population-based data. Mean 3MS scores (overall 95.1) tended to decrease with age and increase with education, however these associations varied among ethnic groups (p< 0.0001) even after adjustment for health, physical disability and occupation attainment. Four factors accounted for 37% of the total variance. Each varied with education and ethnicity; the two most prominent factors also varied with age. Despite relatively narrow distributions in WHIMS, baseline 3MS scores retained associations with age and education. These associations varied among ethnic groups, so that care must be taken in comparing data across populations.

Promoting adherence and retention to clinical trials in special populations: a women's health initiative workshop.

This paper describes a Women's Health Initiative workshop on promoting adherence and retention in randomized clinical trials among ethnic minority women, participants of lower socioeconomic status, and older women. Workshop objectives were: (1) to increase knowledge of demographic and cultural characteristics of diverse groups, (2) to increase awareness of how diversity can affect interactions in clinical research, (3) to explore how research staff behavior can influence adherence and retention, and (4) to increase knowledge of strategies to enhance adherence and retention in special populations. The workshop emphasized the importance of understanding beliefs, values, and experiences that are common in diverse groups of individuals, while at the same time recognizing and respecting individual differences that result from varying life circumstances and experiences. We discuss strategies to increase cultural competence, reduce stereotypes and discrimination, and create a culturally relevant and sensitive research environment.

Why older community-dwelling adults do not discuss urinary incontinence with their primary care physicians.

OBJECTIVES: This study explored reasons why older adults with urinary incontinence (UI) do not initiate discussions with or seek treatment for UI from their primary care provider. DESIGN: A randomized, prospective controlled trial involving 41 primary care sites. SETTING: Primary care practice sites. PARTICIPANTS: 49 older adults age 60 and older not previously screened for UI by their primary care doctor. MEASUREMENTS: Demographic data, self-reported bladder-control information using questionnaires, and health status. RESULTS: Adults who did not discuss UI were older, had less-frequent leaking accidents and fewer nighttime voids and were less bothered by UI than those who did. The two main reasons why patients did not seek help were the perceptions that UI was not a big problem (45%) and was a normal part of aging (19%). CONCLUSIONS: Embarrassment or lack of awareness of treatment options were not significant barriers to discussing UI. Adults with a fairly high frequency of UI (average of 1.7 episodes per day) did not view UI as abnormal or a serious medical condition.

Trust in physicians and medical institutions: what is it, can it be measured, and does it matter?

Despite the profound and pervasive importance of trust in medical settings, there is no commonly shared understanding of what trust means, and little is known about what difference trust actually makes, what factors affect trust, and how trust relates to other similar attitudes and behaviors. To address this gap in understanding, the emerging theoretical, empirical, and public policy literature on trust in physicians and in medical institutions is reviewed and synthesized. Based on this review and additional research and analysis, a formal definition and conceptual model of trust is presented, with a review of the extent to which this model has been confirmed by empirical studies. This conceptual and empirical understanding has significance for ethics, law, and public policy.

Enhancing adherence in randomized controlled clinical trials.

This paper identifies individual and systematic primary, secondary, and tertiary prevention approaches that can be used to enhance adherence in randomized controlled trials. Specifically, strategies such as these are discussed: careful screening during enrollment, use of a run-in period, fully informing participants of the study burden, explaining randomization, determining the participant's prior history with treatment interventions, establishing and using a tracking system, clearly specifying adherence measures, and staff training in communication and negotiation. These strategies have been gathered over time from our experiences working in multiple randomized controlled trials. Research on factors that promote or detract from adherence should be a standard part of randomized controlled trials. Control Clin Trials 2000;21:226S-232S

Disclosure of physician incentives: do practices satisfy purposes?

Under legal pressure, discussion has quickly shifted from whether health plans should disclose how they pay their physicians to how, when, and what should be disclosed and by whom. This paper describes health plans' disclosure practices and evaluates their adequacy and likely impact. It begins by explaining how different reasons for disclosure alter the form and content of disclosure, illustrating these approaches with actual examples. The paper concludes with a recommended approach that attempts to layer and stage disclosures so that people have as much information as they want, when they need it.

Magnetic resonance imaging detection of occult skin and subcutaneous abnormalities in juvenile dermatomyositis. Implications for diagnosis and therapy.

OBJECTIVE: To assess the utility of magnetic resonance imaging (MRI) of skin, subcutaneous tissue, and fascia in evaluating disease activity in juvenile dermatomyositis (DM). METHODS: Short tau inversion recovery (STIR) MRI of the proximal thighs and buttocks, cutaneous assessment, and other measures of disease activity were prospectively obtained in 26 children meeting criteria for probable or definite juvenile DM. Also undergoing STIR MRI assessment were 8 subjects who were being evaluated for muscle disorders and who were not diagnosed as having juvenile DM. RESULTS: Skin, subcutaneous, or fascial edema of the thighs and buttocks were seen on STIR MRI in up to 85% of juvenile DM patients at baseline evaluation compared with no more than 38% of the comparison group without juvenile DM. In juvenile DM, STIR MRI skin and subcutaneous edema scores correlated (r(s) = 0.51, P = 0.008), as did fascial and muscle edema scores (r(s) = 0.58, P = 0.002). Skin global disease activity scores correlated with MRI skin edema scores (r(s) = 0.41, P = 0.04), and serum aldolase levels correlated with both MRI skin and subcutaneous edema scores (r = 0.44 and 0.40, P = 0.03 and 0.05 respectively). The extent and severity of STIR MRI changes in the skin, subcutaneous tissue, and fascia were not predicted by most other measures of juvenile DM disease activity. Five juvenile DM patients with thigh MRI subcutaneous edema developed clinically apparent calcinosis at the same location within 9 months. CONCLUSION: Edema or inflammation in the skin, subcutaneous tissue, and fascia, found on STIR MRI, is common in juvenile DM patients and is often undetected by standard assessments. These MRI changes can precede the development of calcinosis. STIR MRI may be a useful adjunct for assessing disease activity and guiding the treatment of juvenile DM.

The association of depressive symptoms and urinary incontinence among older adults.

OBJECTIVES: To examine the relationship of urinary incontinence (UI) and depressive symptoms (DS) in older adults. DESIGN: A randomized, controlled trial to determine the effects of clinical practice guideline implementation on provider attitudes and behavior, and patients' UI, health status, quality of life, and satisfaction with care. Baseline and endpoint data were collected from patients via computer-assisted telephone interviewing. SETTING: Forty-one nonacademic primary care practices (PCP) in North Carolina. PARTICIPANTS: A total of 668 community-dwelling adults (age > 60) who had visited the one of the selected PCPs. INTERVENTION: PCPs in the intervention group were given instruction in the detection and management of UI, educational materials for providers and patients, office system supports, and academic detailing. MEASUREMENTS: The dependent measure was assessed using an eight-item screener for DS. UI (status, frequency, amount), health (physical, mental), and demographic (age, gender, marital status) and self-report information about bladder control served as predictors. RESULTS: Wilcoxon rank sum tests showed that UI status was associated with moderate to severe DS (43% vs 30%, P = .05). Multivariate analyses showed that UI status, physical and mental health, and gender were significant predictors of DS. Among UI adults (n = 230), physical and mental health, life satisfaction, and the perception that UI interfered with daily life were significant predictors of DS. CONCLUSIONS: This study provides clear evidence that UI is related to DS in older adults.

Communication between older adults and their physicians about urinary incontinence.

BACKGROUND: Urinary incontinence (UI) is a common but undertreated condition in older adults. The study objective was to determine older patients' characteristics related to communication patterns with their physicians about UI. METHODS: Telephone surveys of a sample of patients age 60 and older who visited a primary care provider (PCP) for any reason within the past 2 months were conducted. Participating physicians included general internists and family physicians from 41 primary care practices located in the 17 counties of northwest North Carolina whose 435 incontinent and 711 continent patients completed the surveys. The main outcome measures were patients' frequency and amount of urinary leakage, being asked about incontinence, and initiating a discussion of incontinence if not asked by their PCP. RESULTS: Age and gender were significant independent predictors of incontinence. PCPs were significantly more likely to assess incontinent women than incontinent men (21% vs 10%, p = .053). The older cohorts of older adults were significantly more likely to be symptomatic for UI than their younger counterparts. However, the younger cohorts were more likely to be screened for incontinence by their physicians. CONCLUSIONS: Despite the publication of guidelines on improving the screening and management of UI, the problem remains common and underdetected in older adults. Physicians don't ask and patients don't tell. Interventions are needed to remind physicians to screen high risk patients and to encourage patients with UI to communicate with their physicians.

The quality of life of older adults with urinary incontinence: determining generic and condition-specific predictors.

Urinary incontinence (UI) is an unpleasant problem for many adults. This study determined the importance of demographic, health and incontinence variables for the generic and incontinence-specific quality of life (QoL) of older adults (age > or = 60 years). Telephone surveys of adults reporting at least weekly episodes of UI (n = 435) were conducted as part of a randomized, controlled trial. Logistic regression analyses showed that the predictors of generic and incontinence-specific QoL differed. Life satisfaction, a generic outcome, was predicted by education, the number of days in bed due to health problems, the number of days not feeling well and the amount of urine lost. Generic health was related to education, the number of days sick in the previous 30 days and the number of days health issues restricted activities. The incontinence-specific QoL outcomes were predicted by age, mobility difficulties, the amount of urine lost, the frequency of UI, and the number of daytime and night-time voids. The specific QoL measures provide a different profile of those most affected in this sample than that obtained by the generic measures. The most affected are younger persons with severe urine loss. Older persons may have other conditions impinging on QoL and may have adapted behaviourally and psychologically to urine loss.

Effect of lymphatic and splenic pump techniques on the antibody response to hepatitis B vaccine: a pilot study.

Osteopathic manipulative treatment (OMT) facilitates the movement of lymphatic fluid and may enhance the immunologic response to infection or injected antigen. In this investigation, two groups of volunteers were vaccinated with recombinant hepatitis B vaccine, given at 0, 5, and 25 weeks. The experimental group (n = 20) received OMT (lymphatic and splenic pump) three times per week for 2 weeks after each vaccination. Control subjects (n = 19) received vaccine but no OMT. Resultant serum antibody levels were measured by enzyme immunoassay. Fifty percent of subjects in the treatment group achieved protective antibody titers (> or = 10 mIU/mL) on the 13th week with an average titer of 374 mIU/mL. Only 16% of the control subjects had positive antibody responses, with average titers of 96 mIU/mL. At all time points from week 6 on, the average anti-hepatitis B titer was higher in the treatment group than in the control group. These data suggest an enhanced immunologic response in subjects who received OMT.

Relationship between patient reports of urinary incontinence symptoms and quality of life measures.

OBJECTIVE: To determine if patient reports of urinary incontinence symptoms can predict quality of life as measured by the short forms of the Incontinence Impact Questionnaire and the Urogenital Distress Inventory, two standardized, disease-specific instruments. METHODS: Telephone surveys were conducted of 384 community dwelling incontinent women, aged 60 years and older, who admitted to at least one episode of incontinence per week during the previous 3 months. Subjects were asked if they considered the incontinence a problem, as well as questions regarding volume and frequency of voids and urine loss. Each subject completed both standardized quality of life questionnaires. Responses to incontinence symptom questions were correlated with the standardized measures. RESULTS: The question, "Do you consider this accidental loss of urine a problem that interferes with your day-to-day activities or bothers you in other ways?" was the best predictor of the subject's responses to both quality-of-life measures, with a correlation coefficient of 0.69 for the Incontinence Impact Questionnaire and 0.67 for the Urogenital Distress Inventory. The patients' symptoms that best correlated with both quality of life measures and the report of bothersome incontinence were frequent episodes of incontinence (0.40-0.58), greater amounts of urine loss (0.26-0.54), and more frequent voids (0.24-0.41). CONCLUSION: Primary care practitioners may screen for problematic incontinence by asking if patients' incontinence is bothersome to them and by obtaining simple historic information on voiding and leaking patterns. These questions may provide an efficient tool to detect bothersome incontinence in older women.

Hormone replacement therapy and other potential treatments for dementias.

The past decade has seen a substantial increase in the number of individuals affected by dementia. Dementia places a tremendous personal and economic burden on millions of patients and caregivers annually. Consequently, many scientists have been searching for a treatment for dementia to avoid the imminent public health crisis that will occur if this trend continues. Primary and secondary prevention studies, as well as animal research, demonstrate the potential for hormone replacement therapy (HRT) as an efficacious treatment for dementia. Recently, the Women's Health Initiative-Memory Study began the first randomized, longterm clinical trial to test the hypothesized role of HRT at the onset and in the progression of dementia in women. Researchers also are investigating the potential of other treatments for dementias, such as nonsteroidal anti-inflammatory drugs and free radical scavengers.

Effects of cooperative learning groups during social studies for students with autism and fourth-grade peers.

We investigated the use of cooperative learning groups as an instructional strategy for integrating 2 students with autism into a fourth-grade social studies class. Baseline consisted of 40 min of teacher-led sessions including lecture, questions and discussion with students, and the use of maps. The intervention condition consisted of 10 min of teacher introduction of new material, followed by cooperative learning groups that included tutoring on key words and facts, a team activity, and a whole class wrap-up and review. An ABAB design showed increases for target students and peers for the number of items gained on weekly pretests and posttests, the percentage of academic engagement during sessions, and durations of student interaction during the intervention.

Posttraumatic seizures.

Posttraumatic epilepsy is one of the most clinically disturbing and, to date, difficult predictive factors associated with head trauma. The risk of developing seizures after head trauma depends on several factors. This article explores the mechanisms and biochemical effects of brain injury, their relationship to developing seizures, antiepileptic prophylaxis, and neuroprotective pharmacologic therapy.