Pain and health-related quality of life in people with chronic leg ulcers.

INTRODUCTION: Venous leg ulceration is associated with pain and poor health-related quality of life (HRQL). The purpose of this study was to identify demographic and clinical characteristics associated with pain and decreased HRQL in patients with active venous ulcers. METHODS: Baseline data were combined from two trials that took place between 2001 and 2007 (n = 564). Pain was measured using the Numeric Pain Scale (NPS), and HRQL was measured using the Medical Outcomes Survey 12-item Short Form (SF-12), which generates a Physical (PCS) and Mental Component Summary (MCS). Analyses included logistic and linear regression (for pain and HRQL, respectively). RESULTS: Mean age was 66.5 years; 47% were male. Median NPS score was 2.2 (out of 10) and mean PCS and MCS scores were 38.0 and 50.5, respectively (scores are standardized to a mean of 50 representing average HRQL). Younger age, living with others, and arthritis were associated with pain. Poorer PCS was associated with being female, venous/mixed ulcer etiology, larger ulcers, longer ulcer duration, cardiovascular disease, arthritis and higher pain intensity. Poorer MCS was associated with younger age, longer ulcer duration, comorbidity and higher pain intensity. CONCLUSION: Research is needed to test strategies to reduce pain and possibly improve HRQL in high risk groups.

TITLE: Douleur et qualité de vie liée à la santé chez les personnes souffrant d'ulcères chroniques aux jambes. INTRODUCTION: L'ulcération veineuse de la jambe est associée à de la douleur et à une mauvaise qualité de vie liée à la santé (QVLS). Cette étude visait à définir les caractéristiques démographiques et cliniques associées à la douleur et à une diminution de la QVLS chez les patients présentant des ulcères veineux actifs. MÉTHODOLOGIE: Les données de base obtenues dans le cadre de deux essais menés entre 2001 et 2007 (n = 564) ont été combinées. La douleur a été mesurée à l'aide de l'échelle numérique de la douleur (END), et la QVLS a été mesurée à l'aide du formulaire abrégé comportant 12 questions de l'Enquête sur la santé (SF-12), qui produit un sommaire de la composante physique (SCP) et un sommaire de la composante mentale (SCM). Les analyses ont notamment été effectuées par régression logistique (pour la douleur) et par régression linéaire (pour la QVLS). RÉSULTATS: L'âge moyen était de 66,5 ans; 47 % étaient des hommes. Le score médian sur l'END était de 2,2 (sur 10) et les scores moyens du SCP et du SCM étaient respectivement de 38,0 et de 50,5 (les scores sont normalisés à une moyenne de 50, qui représente la QVLS moyenne). Le jeune âge, le fait de vivre avec d'autres personnes et l'arthrite ont été associés à la douleur. Un score plus faible pour le SCP a été associé au fait d'être une femme, aux ulcères d'origine veineuse/mixte, aux gros ulcères, aux ulcères de longue durée, aux maladies cardiovasculaires, à l'arthrite et la douleur intense. Un score plus faible pour le SCM a été associé au jeune âge, aux ulcères de longue durée, aux affections concomitantes et à la douleur intense. CONCLUSION: Il convient de mener des recherches pour mettre à l'essai des stratégies d'atténuation de la douleur et d'amélioration potentielle de la QVLS chez les groupes à risque élevé.

CAG repeat expansion in Huntington disease determines age at onset in a fully dominant fashion.

OBJECTIVE: Age at onset of diagnostic motor manifestations in Huntington disease (HD) is strongly correlated with an expanded CAG trinucleotide repeat. The length of the normal CAG repeat allele has been reported also to influence age at onset, in interaction with the expanded allele. Due to profound implications for disease mechanism and modification, we tested whether the normal allele, interaction between the expanded and normal alleles, or presence of a second expanded allele affects age at onset of HD motor signs. METHODS: We modeled natural log-transformed age at onset as a function of CAG repeat lengths of expanded and normal alleles and their interaction by linear regression. RESULTS: An apparently significant effect of interaction on age at motor onset among 4,068 subjects was dependent on a single outlier data point. A rigorous statistical analysis with a well-behaved dataset that conformed to the fundamental assumptions of linear regression (e.g., constant variance and normally distributed error) revealed significance only for the expanded CAG repeat, with no effect of the normal CAG repeat. Ten subjects with 2 expanded alleles showed an age at motor onset consistent with the length of the larger expanded allele. CONCLUSIONS: Normal allele CAG length, interaction between expanded and normal alleles, and presence of a second expanded allele do not influence age at onset of motor manifestations, indicating that the rate of HD pathogenesis leading to motor diagnosis is determined by a completely dominant action of the longest expanded allele and as yet unidentified genetic or environmental factors.

Guideline adaptation: an approach to enhance efficiency in guideline development and improve utilisation.

BACKGROUND: Developing and updating high-quality guidelines requires substantial time and resources. To reduce duplication of effort and enhance efficiency, we developed a process for guideline adaptation and assessed initial perceptions of its feasibility and usefulness. METHODS: Based on preliminary developments and empirical studies, a series of meetings with guideline experts were organised to define a process for guideline adaptation (ADAPTE) and to develop a manual and a toolkit made available on a website (http://www.adapte.org). Potential users, guideline developers and implementers, were invited to register and to complete a questionnaire evaluating their perception about the proposed process. RESULTS: The ADAPTE process consists of three phases (set-up, adaptation, finalisation), 9 modules and 24 steps. The adaptation phase involves identifying specific clinical questions, searching for, retrieving and assessing available guidelines, and preparing the draft adapted guideline. Among 330 registered individuals (46 countries), 144 completed the questionnaire. A majority found the ADAPTE process clear (78%), comprehensive (69%) and feasible (60%), and the manual useful (79%). However, 21% found the ADAPTE process complex. 44% feared that they will not find appropriate and high-quality source guidelines. DISCUSSION: A comprehensive framework for guideline adaptation has been developed to meet the challenges of timely guideline development and implementation. The ADAPTE process generated important interest among guideline developers and implementers. The majority perceived the ADAPTE process to be feasible, useful and leading to improved methodological rigour and guideline quality. However, some de novo development might be needed if no high quality guideline exists for a given topic.

Health Heritage© a web-based tool for the collection and assessment of family health history: initial user experience and analytic validity.

A detailed family health history is currently the most potentially useful tool for diagnosis and risk assessment in clinical genetics. We developed and evaluated the usability and analytic validity of a patient-driven web-based family health history collection and analysis tool. Health Heritage(©) guides users through the collection of their family health history by relative, generates a pedigree, completes risk assessment, stratification, and recommendations for 89 conditions. We compared the performance of Health Heritage to that of Usual Care using a nonrandomized cohort trial of 109 volunteers. We contrasted the completeness and sensitivity of family health history collection and risk assessments derived from Health Heritage and Usual Care to those obtained by genetic counselors and genetic assessment teams. Nearly half (42%) of the Health Heritage participants reported discovery of health risks; 63% found the information easy to understand and 56% indicated it would change their health behavior. Health Heritage consistently outperformed Usual Care in the completeness and accuracy of family health history collection, identifying 60% of the elevated risk conditions specified by the genetic team versus 24% identified by Usual Care. Health Heritage also had greater sensitivity than Usual Care when comparing the identification of risks. These results suggest a strong role for automated family health history collection and risk assessment and underscore the potential of these data to serve as the foundation for comprehensive, cost-effective personalized genomic medicine.

Associations between chronic disease, age and physical and mental health status.

This paper examines the associations between chronic disease, age, and physical and mental health-related quality of life (HRQOL), using data collected in 10 studies representing five chronic conditions. HRQOL was measured using the SF-36 or the shorter subset, SF-12. Physical Component Summary (PCS) and Mental Component Summary (MCS) scores were graphed by condition in age increments of 10 years, and compared to age- and sex-adjusted normative data. Linear regression models for the PCS and MCS were controlled for available confounders. The sample size of 2418 participants included 129 with renal failure, 366 with osteoarthritis (OA), 487 with heart failure, 1160 with chronic wound (leg ulcer) and 276 with multiple sclerosis (MS). For the PCS, there were large differences between the normative data and the mean scores of those with chronic diseases, but small differences for the MCS. Female gender and comorbid conditions were associated with poorer HRQOL; increased age was associated with poorer PCS and better MCS. This study provided additional evidence that, while physical function could be severely and negatively affected by both chronic disease and advanced age, mental health remained relatively high and stable.

A multifaceted intervention to improve treatment of osteoporosis in postmenopausal women with wrist fractures: a cluster randomized trial.

UNLABELLED: In a cluster randomized trial, we evaluated the effect of a multifaceted intervention (directed at both patient and primary care physician) on the rates of testing and treatment of osteoporosis in postmenopausal women within six months of their wrist fracture. Compared to usual care, women in the intervention practices were three times more likely to receive bone mineral density testing and prescribed osteoporosis treatments. INTRODUCTION: Postmenopausal women with wrist fractures are at increased risk of future fragility fractures, yet they frequently do not receive evaluation and treatment for osteoporosis. We set out to evaluate a multifaceted intervention designed to improve management of osteoporosis in older women with recent wrist fractures. METHODS: Cluster randomized trial of 270 women cared for in 119 primary care practices. We recruited postmenopausal women with an acute wrist fracture from the emergency departments of hospitals in southeastern Ontario, Canada. Family practices were randomly assigned to either the intervention or usual care. The intervention consisted of a mailed reminder with a summary of treatment guidelines and letter sent to the primary care physician, in addition to an educational package and letter to the women. The primary outcome was the proportion of women prescribed osteoporosis therapy within 6 months of their fracture. RESULTS: The mean age of women was 69(10.9) years. The intervention increased the proportion of women started on osteoporosis medications (28% vs. 10%) of controls, adjusted OR 3.45, 95% CI, 1.58-7.56, p = 0.002) and the proportion who had a bone mineral density (BMD) test (53.3% vs. 26%) of controls, OR 3.38, 95% CI, 1.83-6.26, p < 0.001). In addition to the intervention, having a female physician was a predictor of increased testing and treatment rates. CONCLUSION: A multifaceted intervention significantly improved rates of osteoporosis treatment and BMD testing in postmenopausal women with wrist fractures.

Pain in pure and mixed aetiology venous leg ulcers: a three-phase point prevalence study.

OBJECTIVE: This study aimed to determine the point prevalence of venous leg ulcer pain over three seasons (autumn, winter and spring). It also collated profiles of individuals with venous ulceration and described the characteristics of people with and without venous leg ulcer pain. METHOD: The study sample comprised 255 people with pure and mixed venous leg ulcers who were receiving care in a Canadian community leg ulcer service. Prevalence was determined by the number of individuals who had experienced pain in the past 24 hours. The profile of individuals was developed by analysing sociodemographic, circumstance-of-living, clinical and health-related quality-of-life data collected on admission to the leg ulcer service. RESULTS: Over the three prevalence periods, the prevalence of pain for the total sample ranged from 48% to 54%. Prevalences at each of the study periods for individuals who had been receiving care for less than 13 weeks, and for the first measure of pain only, were almost identical, ranging from 48-59%. The mean pain-severity score was less than three (out of 10) in all three periods. Of the individuals with pain, 50% or more used analgesia and, of these, over 75% reported it was effective. The profile of participants with pain was similar to those without it, except that the former were significantly more likely to have osteoarthritis, a foot ulcer, to have been attending the leg service for a shorter time period and to have a lower SF-12 mental health component score. CONCLUSION: These results demonstrate that leg ulcer management must include pain assessment and consideration of the factors that may be associated with pain. A large prospective repeated measures study is needed to increase understanding of the extent of pain, the use and efficacy of analgesia, and the factors that may be related to experiencing pain.

Destruction of midbrain dopaminergic neurons by using immunotoxin to dopamine transporter.

1. The ability to target specific neurons can be used to produce selective neural lesions and potentially to deliver therapeutically useful moieties for treatment of disease. In the present study, we sought to determine if a monoclonal antibody to the dopamine transporter (anti-DAT) could be used to target midbrain dopaminergic neurons. 2. The monoclonal antibody recognizes the second, large extracellular loop of DAT. The antibody was conjugated to the "ribosome-inactivating protein"; saporin, and stereotactically pressure microinjected into either the center of the striatum or the left lateral ventricle of adult, male Sprague-Dawley rats. 3. Local intrastriatal injections produced destruction of dopaminergic neurons in the ipsilateral substantia nigra consistent with suicide transport of the immunotoxin. Intraventricular injections (i.c.v.) produced significant loss of dopaminergic neurons in the substantia nigra and ventral tegmental area bilaterally without evident damage to any other aminergic structures such as the locus coeruleus and raphe nuclei. To confirm the anatomic findings, binding of [3-H]mazindol to DAT in the striatum and midbrain was assessed using densitometric analysis of autoradiograms. Anti-DAT-saporin injected i.c.v. at a dose of 21 microg, but not 8 microg, produced highly significant decreases in mazindol binding consistent with loss of the dopaminergic neurons. 4. These results show that anti-DAT can be used to target midbrain dopaminergic neurons and that anti-DAT-saporin may be useful for producing a lesion very similar to the naturally occurring neural degeneration seen in Parkinson's disease. Anti-DAT-saporin joins the growing list of neural lesioning agents based on targeted cytotoxins.

Increased neurosteroid sensitivity of hippocampal GABAA receptors during postnatal development.

To investigate developmental changes in neurosteroid modulation of GABA(A) receptors, whole-cell currents were elicited by applying GABA with allopregnanolone or pregnenolone sulfate (PS) to dentate granule cells (DGCs), acutely isolated from 7-14-day-old and adult rats. GABA evoked larger currents from dentate granule cells acutely isolated from adult rats (adult DGCs) than from neonatal DGCs, due to increased efficacy (1662+/-267 pA in adult DGCs versus 1094+/-198 pA in neonatal DGCs, P=0.004), and current density (0.072+/-0.01 pA/microm(2) in neonatal rat DGCs to 0.178+/-0.02 pA/microm(2) in adult DGCs), but unchanged potency (EC(50) was 18.5+/-2 microm in adult DGCs, and 26.6+/-7.9 microm in neonatal DGCs, P=0.21). Allopregnanolone sensitivity of GABA(A) receptor currents increased during development due to an increased potency (21.1+/-4.7 nM in adult DGCs versus 94.6+/-9 nM in neonatal DGCs, P=0.0002). The potency and efficacy of PS inhibition of GABA(A) receptor currents were remained unchanged during development (13+/-6 microm and 13.2+/-5.9 microm, P=0.71 and 85.5%+/-3.5% and 83.6%+/-0.8%, P=0.29, respectively). To investigate possible mechanism of developmental changes in GABA(A) receptor properties, in situ hybridization for alpha1, alpha4 and gamma2 subunit mRNAs was performed in dentate gyrus of the two age groups. Qualitatively, alpha1 subunit mRNA was expressed at low levels in neonatal rats while it was well expressed in adult rats. The alpha4 and gamma2 subunits were well expressed in the dentate gyrus of adult and neonatal rats. Immunohistochemical staining for alpha1 subunit in hippocampal slices from neonatal and adult rats was examined under confocal laser scanning microscope. This demonstrated that cell bodies and dendrites of granule cells are moderately positive for the alpha1 staining in adult rats but weakly so in neonatal rats. Higher-magnification images demonstrate large number of clusters of alpha1-subunit in the cell bodies of dentate granule cells of adult rat but rare clusters in granule cells of neonatal rats. Maturation of GABA(A) receptors in DGCs is characterized by increased number of GABA(A) receptors that are more sensitive to endogenous neurosteroid allopregnanolone, which might be related to increased expression of alpha1 subunit.

The impacts of distance to hospital on families with a child with a chronic condition.

Children with chronic conditions and their families face many similar challenges that can be stressful for the family including, daily caregiving activities, financial difficulties caused by unexpected expenses, and increased use of health services to treat and help manage the condition. Many of these families, in addition to facing daily caregiving responsibilities, must travel substantial distances to access some of the necessary aspects of their child's health care. In this study, the Burke et al. (1994-1996) data of repeatedly hospitalized children and their families are used to explore a geographical dimension of family impact, distance. Outcome measures from the Feetham Family Functioning Survey and the Questionnaire on Resources and Stress are analyzed using exploratory and multivariate analysis. Results show that distance to hospital plays a role in the two areas of family life regarding relationships within the immediate family, and issues surrounding the ability to maintain the child in the family home. The implications of the results for family, health care intervention, and government policies and guidelines are discussed.

Gender ratio differences between Parkinson's disease patients and their affected relatives.

Mitochondrial dysfunction in Parkinson's disease (PD) is suspected to arise from either acquired or inherited mutation of mitochondrial DNA (mtDNA). If inherited, epidemiologic analysis may reveal maternal transmission. We looked for maternal inheritance bias in our PD clinical database. About 13% of 600 PD probands reported an affected parent. Although 60% of the PD probands were male, only 42% of the affected parents were. The gender ratios for the proband and affected parent generations were dissimilar (p<0.005), indicating an underrepresentation of affected fathers or an overrepresentation of affected mothers. To address these possibilities we analyzed a non-PD control cohort. Four percent of the controls had a PD affected parent, and 75% of these affected parents were male. Apparent maternal inheritance bias in our PD cohort is therefore more likely due to overrepresentation of affected mothers, and is consistent with mitochondrial inheritance in some of our ascertained cases.

Clinical practice guidelines: necessary but not sufficient for evidence-based patient education and counseling.

While clinical practice guidelines provide direction for the management of specific diseases or particular clinical problems, there are major gaps between guidelines and their implementation. The purpose of this paper is to illustrate how an existing guideline can be used to develop an evidence-based patient education program. Congestive heart failure (CHF) represents a range of complex, chronic illnesses which offer little hope of cure yet require symptom management by health care providers, patients, and their families. Successful self-monitoring, self-care, and decision making are based on acquisition of appropriate knowledge and management skills. We describe a comprehensive teaching program in which the content was built on the clinical evidence from the Agency for Health Care Policy and Research recommendations for CHF, and the implementation process was built on adult education evidence, adapted to health issues and patient learning challenges.

Early changes in neuropeptide mRNA expression in the striatum following reserpine treatment.

Chronic dopamine depletion produces neurochemical changes within the striatum as well as enhanced behavioral and metabolic responses to dopamine agonists. Changes in striatal neuropeptides have been consistently described, including increased expression of preproenkephalin mRNA and decreased expression of preprotachykinin and prodynorphin mRNA. Acute dopamine depletion following treatment with reserpine also produces enhanced behavioral and metabolic responses to agonist treatment which develop rapidly. In the present study, we used in situ hybridization histochemistry to investigate whether acute neurochemical changes occur following reserpine treatment. We evaluated neuropeptide mRNA expression in the striatum and nucleus accumbens at several time points from 6 to 120 h following single doses of reserpine and AMPT. The aim of these studies was to determine if changes in neuropeptide mRNA expression occur following acute dopamine depletion and whether such changes are specific to the striatum. Changes in striatal neuropeptide mRNA expression developed rapidly. Preproenkephalin mRNA expression by striatopallidal neurons was unchanged at 48 h, but increased by 44% at 120 h. Preprotachykinin mRNA expression in striatonigral neurons was increased at 6 h and then fell, with a maximal decrease of 45% at 48 h and partial recovery by 120 h. Prodynorphin mRNA expression was unchanged. Expression of preproenkephalin and preprotachykinin mRNA was also examined in subregions of the striatum and the nucleus accumbens. Expression of preproenkephalin mRNA was uniform in the striatum and higher in the core than the shell of the nucleus accumbens. Preprotachykinin mRNA expression in the striatum was higher in the lateral quadrants and was higher in the shell than in the core of the nucleus accumbens. The changes in neuropeptide mRNA following treatment with reserpine were only found in the striatum. These data provide further evidence for early alterations in neuronal function in the striatum following acute dopamine depletion and suggest that neuropeptide expression by striatonigral neurons may be more rapidly regulated in response to changes in dopamine levels.

Canadian oncologists and clinical practice guidelines: a national survey of attitudes and reported use. Provincial Lung Disease Site Group of Cancer Care Ontario.

PURPOSE: To determine (1) Canadian oncologists' attitudes toward practice guidelines, (2) oncologists' self-reported use of practice guidelines and, (3) physicians' characteristics and attitudes associated with self-reported use of practice guidelines. PARTICIPANTS AND METHODS: A cross-sectional, self-administered postal survey was administered to Canadian oncologists. Main outcome measures were level of agreement with 8 descriptive statements about guidelines, score on the attitudinal scale of the guideline of Tunis et al., and physicians' stated use of guideline. chi(2) and logistic regression procedures were used to explore the relationship between physician characteristics and use of guidelines. RESULTS: Over 80% of respondents agreed that they were good educational tools, convenient sources of advice, intended to improve quality of care; over 40% agreed that they were unbiased syntheses of expert opinion. Conversely, 42, 26, 20 and 16% felt they were intended to cut costs, were oversimplified cookbook medicine, were too rigid to apply to individual patients, and a challenge to physicians' authority, respectively. Forty-one percent reported using practice guidelines routinely or most of the time. Use was associated with positive attitudes about guidelines, receiving medical school training abroad and being a radiation oncologist. CONCLUSION: Canadian oncologists were quite positive about practice guidelines and reported using them frequently. Our results suggest that use of guidelines by oncologists may be related to attitudes about guidelines in general, specialty within oncology and country of medical school training.

Parents' perceptions of chronic illness trajectories.

The notion of a small, generic set of chronic illness trajectories that can be independent of specific medical diagnoses, though controversial, has some theoretical, clinical, and qualitative research support. The purpose of this study was to quantitatively describe trajectories among parents of children with a chronic condition. It was hypothesized that factor analysis would confirm 3 trajectories similar to those in the qualitative literature and that parents' perceptions of their child's trajectory would differ significantly from medically based perceptions. A total of 140 parents provided data on their perceptions of the past, present, and future course of the condition of their repeatedly hospitalized child. Fourteen time-related items from the Coping Health Inventory for Parents Questionnaire on Resources and Stress and the Parenting Stress Index were analyzed. Pre- and post-hospitalization factor analyses extracted the same 8 items to construct 3 trajectories: Life Threatening; Declining; and Stable, Optimistic. The views of approximately one third of the parents differed from medically based classifications. Type of nursing care had no bearing on the perceptions of the parents.