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.

Clinical correlates of sleep benefit in Parkinson's disease.

The phenomenon of sleep benefit, a period of lessened disability or feeling "on" upon awakening from sleep in the morning, has received scant attention in the literature on Parkinson's disease. We interviewed 162 consecutive patients regarding disease onset, medication history, and symptoms, evaluated them using the Unified Parkinson's Disease Rating Scale, and assessed them as to the presence or absence of sleep benefit. Thirty-three percent reported experiencing sleep benefit. Compared with patients not having sleep benefit, patients with sleep benefit tended to be younger at disease onset, have longer disease duration, take higher total daily doses of levodopa, have longer duration of levodopa treatment, and exhibit less cognitive and physical disability. The findings of this study suggest that sleep benefit is a common phenomenon that may be anticipated in a subgroup of patients with Parkinson's disease. The mechanisms underlying sleep benefit do not appear to be simple and may be multifactorial. Clinicians need to be aware of the authenticity of patients' reports of sleep benefit and consider the existence of this phenomenon when prescribing or adjusting patients' medication schedules.

Early morning dystonia in Parkinson's disease.

We interviewed 383 patients with PD regarding disease onset and medication history and evaluated them using the Unified Parkinson's Disease Rating Scale. Sixteen percent of the sample reported the occurrence of early morning dystonia (EMD). Patients with EMD had been taking levodopa for a longer time, were taking higher daily levodopa doses, demonstrated more disability in carrying out their activities of daily living, exhibited dystonia more often before initiation of levodopa treatment, and experienced more peak-dose and diphasic dyskinesias with levodopa therapy.

Opioid peptide expression in models of chronic temporal lobe epilepsy.

Expression of the opioid peptides dynorphin and enkephalin is altered within the first 24 h after acutely induced seizures in certain experimental models of epilepsy. Using in situ hybridization, we examined the expression of prodynorphin and preproenkephalin messenger RNA acutely following induction of kindling with recurrent seizures and in two models of chronic temporal lobe epilepsy: (i) rats fully kindled with rapidly recurring hippocampal seizures; and (ii) rats surviving after self-sustaining limbic status epilepticus induced with focal electrical stimulation of the hippocampus. In naive animals, a ventral-dorsal gradient was identified in the expression of both prodynorphin and preproenkephalin messenger RNA in the dentate gyrus and expression of prodynorphin message was demonstrated for the first time in the ventral portion of cornu Ammonis regio superior. After stimulation producing rapidly recurring hippocampal seizures, acute decreases in prodynorphin messenger RNA were seen in the dentate gyrus and cornu Ammonis regio superior at 24 h after the last seizure. In contrast, increases in preproenkephalin messenger RNA expression were seen acutely in the dentate gyrus, with a decrease seen in the entorhinal cortex. The change in prodynorphin message expression in cornu Ammonis regio superior persisted in kindled animals that were studied after one month seizure-free period. There were no changes in preproenkephalin message in kindled animals studied after the one month seizure-free interval. No statistically significant changes were found for either prodynorphin or preproenkephalin message in the post-self-sustaining limbic status epilepticus group at one month following induced seizures. Acute changes in peptide expression may contribute to increased excitation in the dentate gyrus during induction of kindling, while the chronic change identified in cornu Ammonis regio superior may contribute directly to persistently increased excitability in this region.

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.

A D1 dopamine agonist stimulates acetylcholine release from dissociated striatal cholinergic neurons.

We tested the hypothesis that a D1 dopamine agonist could stimulate acetylcholine release directly from striatal cholinergic neurons. A suspension of viable dissociated striatal cells was made enzymatically and mechanically from normal adult male rats. The heterogeneous suspension was incubated in [3H]choline to allow synthesis of [3H]acetylcholine selectively by cholinergic neurons. Fractional [3H]acetylcholine release from the cholinergic cells in the suspension was recorded during continuous dynamic perifusion. The D1 agonist, 50 microM (+/-) SKF 38393, increased the basal rate of release from the cholinergic cells by 50% and the action was inhibited by the D1 antagonist, SKF 83566. Stimulation of [3H]acetylcholine secretion was recorded as low as 500 nM SKF 38393. The (S, -) SKF 38393 stereoisomer was significantly less effective than the (R, +) isomer in stimulating release. The D1-mediated stimulation of acetylcholine secretion was abolished in a low-calcium environment that also inhibited basal release. The data suggest that striatal cholinergic cells express D1 receptors functionally coupled to the regulation of acetylcholine release. These D1 actions in the absence of synaptic circuitry imply that such circuitry is not required in situ. In vivo however, indirectly mediated D1 actions and those of other transmitters may modify the manifestations of this direct cholinergic stimulation.

Acute dopamine depletion potentiates independent stimulatory and inhibitory D1 DA receptor-mediated control of striatal acetylcholine release in vitro.

Fractional release of [3H]ACh was evaluated under basal and evoked conditions in striatal slices from normal and acutely dopamine-depleted adult rats for the influence of D1- and D2-DA receptor agonists. The D1 ligand had no effect on normal slices but DA depletion unmasked two independent but simultaneous supersensitive responses: augmentation of K(+)-evoked and inhibition of glutamate-evoked release. The D2 ligand inhibited evoked release in normal slices and this effect was not potentiated. This is a new cholinergic model of acute D1 receptor supersensitivity.

Expression of m1 and m4 muscarinic receptor mRNA in the striatum following a selective lesion of striatonigral neurons.

Cholinergic stimulation has opposing effects on striatopallidal and striatonigral neurons. Most striatal projection neurons express m1 muscarinic receptor mRNA with m4 mRNA found in 40-50%. Expression of m4 mRNA is found in most preprotachykinin neurons but only a subset of preproenkephalin neurons, suggesting preferential localization of m4 receptors to striatonigral neurons. A volkensin lesion of striatonigral neurons reduced striatal m4 mRNA by 63% and m1 mRNA by only 18%, suggesting that preferential expression of m4 receptors by striatonigral neurons may contribute to their differential response.

A selective lesion of striatonigral neurons decreases presynaptic binding of [3H]hemicholinium-3 to striatal interneurons.

We have used the suicide transport agent, volkensin, to produce selective lesions of striatal efferent neurons projecting to the substantia nigra in the rat. In order to evaluate potential trans-synaptic effects, we examined cholinergic interneurons intrinsic to the striatum following destruction of striatonigral projection neurons by nigral injection of volkensin. There was no change in the number of large interneurons identified either by Nissl stain or by immunocytochemistry for choline acetyltransferase, indicating that volkensin was not directly toxic to this group of neurons. However, [3H]hemicholinium-3 binding to the choline re-uptake site on the presynaptic cholinergic terminals decreased. No change in [3H]hemicholinium-3 binding was seen after destruction of dopaminergic afferents with 6-hydroxydopamine. Striatonigral afferents to the cholinergic interneurons contain substance P which has been shown to stimulate acetylcholine release. The decrease in [3H]hemicholinium-3 binding may reflect loss of this afferent input. However, striatonigral neurons are an efferent target of the cholinergic interneuron as well, and a presynaptic effect due to loss of target neurons also may contribute.

Changes in D2 but not D1 receptor binding in the striatum following a selective lesion of striatopallidal neurons.

We have used the immunotoxin OX7/saporin, a suicide transport agent, to selectively lesion striatopallidal neurons. Following injection of OX7/saporin into the globus pallidus, in situ hybridization for preproenkephalin mRNA was examined in the striatum to confirm successful retrograde neurotoxicity. Comparison of D1 and D2 receptor binding in the striatum demonstrated that D2 but not D1 receptor binding sites are localized to striatopallidal neurons.

The time course of changes in D1 and D2 receptor binding in the striatum following a selective lesion of striatonigral neurons.

The suicide transport agent volkensin was used to produce a selective lesion of striatonigral projection neurons and the time course of changes in binding at striatal D1 and D2 receptors analyzed. Both show a time-dependent decrease with two-thirds of the total change occurring within the first 10 days and a greater decrease in D1 receptor density at all time points. Our results confirm selective localization of D1 receptors to striatonigral neurons and are consistent with localization of some striatal D2 receptors to striatonigral neurons.

Selective localization of striatal D1 receptors to striatonigral neurons.

A new technique for producing anatomically selective lesions within the brain was used to investigate the cellular localization of the D1 and D2 receptor. The cytotoxic lectin, volkensin, is taken up by nerve terminals and retrogradely transported, killing those neurons projecting to the site of injection. Comparison of D1 and D2 binding following a unilateral volkensin injection into the substantia nigra has demonstrated that striatal D1 binding sites are selectively localized to striatonigral projection neurons.

Differential localization of A2a adenosine receptor mRNA with D1 and D2 dopamine receptor mRNA in striatal output pathways following a selective lesion of striatonigral neurons.

We have used the suicide transport agent volkensin to produce selective lesions of striatonigral neurons. By in situ hybridization histochemistry unilateral volkensin injections in the substantia nigra decreased the number of D1 receptor mRNA-expressing neurons in the ipsilateral striatum but did not change the number of D2 receptor and A2a adenosine receptor mRNA-expressing neurons. These findings confirm that striatonigral neurons express D1 receptors and suggest that D2-A2a receptor expressing neurons are predominantly localized to other neuronal populations within the striatum.

Acetylcholine release from dissociated striatal cells.

To study the regulation of striatal acetylcholine (ACH) release, adult male rat striata were dissociated and incubated with 3H-choline to synthesize 3H-ACH. Fractional 3H-ACH efflux per min during continuous perifusion was: (1) tightly regulated; (2) dependent on calcium influx; (3) stimulated by 10 mM K+ and 1 mM glutamate; and (4) comparable to ACH release detected by HPLC. Thus, acutely dissociated striata exhibit calcium-sensitive, voltage-dependent secretion of 3H-ACH and direct receptor-mediated stimulation of release through the glutamate receptor family. This new approach toward cholinergic secretory physiology will help clarify complex striatal circuitry.

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.

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.

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.

Quality of life as an outcome measure in nursing research. "May you have a long and healthy life".

Quality of life has emerged as an important concept and outcome in health and health care. Policy-makers, researchers, clinicians, and the public at large consider perceived quality of life to be an important dimension of the health of a population or an individual. The nature of nursing is such that many of its anticipated outcomes relate to improvement in the quality of life of individuals and populations. There continues to be debate about the actual definition of quality of life, and a concept that is difficult to define will naturally pose challenges to measurement. This has not impeded the proliferation of quality-of-life instruments, since the concept is recognized as an increasingly important clinical and research outcome. Progress has been made in clarifying and operationalizing the concept. We propose a conceptual viewpoint that separates what quality of life is from what contributes to quality of life. This will assist nurse researchers planning to use quality of life as an outcome in evaluating nursing interventions. In clinical or research situations, for the purposes of measurement, an operational definition of quality of life stems from a definition of health. From this is drawn a definition of health-related quality of life (HRQL). For the purpose of outcome measurement, the operational definition relates to the domains important to the study population and the particular health intervention under study. Issues that arise in the measurement of HRQL are also presented.

Evidence-based pressure-ulcer practice: the Ottawa model of research use.

Developing evidence-based nursing practice among diverse health-care settings is a particular challenge in the face of current health-care restructuring. This paper describes application of the Ottawa Model of Research Use (OMRU) to increase evidence-based practice across 3 health-care settings during a time of multiple restructuring changes. The initiative was part of a provincial demonstration project to develop centers of nursing excellence with a view to improving continuity of care across the health continuum. Three Ottawa health-care agencies formed one of 4 participating sites in the Province-Wide Nursing Project (PWNP), a 3-year initiative funded by the Ontario Ministry of Health. The goal of the Ottawa-Carleton site was to increase evidence-based decision-making with a focus on pressure ulcers. The barriers and supports encountered, and the strategies used, in striving to meet this goal in a community-care, tertiary-care, and long-term-care setting are described. Multiple research transfer approaches were used, with an emphasis on education. Implementor consensus and achievements of the project support the OMRU's utility as a guide to implementing research findings in these health-care settings.