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Benefits and obstacles of health status assessment in ambulatory settings. The clinician's point of view. The Dartmouth Primary Care COOP Project.

In the past decade physicians have identified the need to expand patient assessment to include global function and quality of life. During the same period, the busy clinic has evolved into the location where this assessment seems most appropriate. Integrating functional health assessment into a busy clinical practice is difficult because the necessary steps require time, thought, recording, and follow-up. Attention to the office ecosystem is very important before any patient care management method is introduced. The clinician must transform the results of health status screening into a specific functional diagnosis. The clinician has to understand the sensitivity, specificity, and predictive value of the measure for a preliminary diagnosis to be made. Often, additional measurements must be taken to establish a specific diagnosis. These steps encompass assessment linkage. Once the specific cause for the dysfunction is recognized, the clinician then has to determine the need for special resources. This is called the resource linkage. By following the steps outlined in this paper, the clinician should be able to overcome many obstacles for functional health status assessment in busy ambulatory settings.

Activities of Daily Living↗

Quantitative assessment of right ventricular structural abnormalities by right ventricular polar mapping of single photon emission computed tomogram.

The identification of right ventricular (RV) abnormalities is clinically important in the evaluation of arrhythmogenic substrates in right ventricular-originated ventricular tachycardia (RVT). The purpose of this study was to determine the diagnostic benefit of quantitative analysis in RV single photon emission computed tomography (SPECT) imaging with (99m)Tc-tetrofosmin/sestamibi in patients with RVT. Thirty patients with RVT (15 with idiopathic RVT and 15 with arrhythmogenic right ventricular cardiomyopathy (ARVC)) were compared with 27 control subjects (including 11 with right bundle branch block) with regard to the semiquantitative RV uptake score in each of six segments and the quantitative RV extent score in polar coordinate map displays by SPECT imaging. The RV total score and RV extent score were compared with the RV global function. Perfusion abnormalities were more frequently detected (P = 0.0001) in the ARVC group (59/90, 65.6%) than in the idiopathic RVT group (4/90, 4.4%) or controls (1/162, 0.6%). The RV extent score in the ARVC group (53.0 +/- 24.8) was significantly higher than that in the idiopathic RVT group (8.4 +/- 10.1) or controls (1.2 +/- 4.9). The RV extent score correlated well with the regional RV perfusion score (P < 0.0001) and with the RV ejection fraction (P < 0.0001). Non-invasive RV perfusion mapping using a (99m)Tc-labelled tracer is useful for the quantitative evaluation of RV substrates in patients with ARVC.

Adolescent↗

Effects of chronic hypoxia on the circulating and pancreatic renin-angiotensin system.

INTRODUCTION: The circulating renin-angiotensin system (RAS) plays a crucial role in the regulation of blood pressure, electrolytes, and fluid homeostasis. In contrast to the circulating RAS, the presence of an intrinsic RAS has been demonstrated in different tissues/organs, which may affect both local and global functions of a biologic system. Our previous studies provided solid evidence of the existence of a local RAS in rat pancreas. Our further investigation showed that such a pancreatic RAS could be activated by experimental models of chronic hypoxia and chemically induced pancreatitis. These previous findings formed the basis for the current study. METHODOLOGY: Adult Sprague-Dawley rats were exposed to isobaric hypoxia (10% O2), and the effects on the circulating and pancreatic RAS were documented. RESULTS: The current study shows that exposure of rats to isobaric hypoxia caused a time-dependent increase in plasma renin activity. The activation of circulating RAS by hypoxia was associated with a parallel upregulation of local RAS components, including the mRNA expression of angiotensinogen and angiotensin II receptor types I and II in the pancreas. CONCLUSION: The upregulation of local pancreatic RAS, along with its counterpart circulating RAS, may be responsible for both physiologic and pathophysiologic aspects of a biologic system under chronic hypoxic stress.

Angiotensinogen↗

Psychosocial service utilization by patients with bipolar disorders: data from the first 500 participants in the Systematic Treatment Enhancement Program.

OBJECTIVE: Although patients with bipolar disorder have been shown to benefit from psychosocial interventions, the proportion that utilizes these interventions is unknown. We set out to clarify the determinants of psychosocial service utilization in adults with bipolar disorder. METHOD: We investigated psychosocial service utilization among the first 500 patients admitted to the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). RESULTS: In the 3 months prior to enrollment in STEP-BD, a majority of the patients (54%) were engaged in at least one psychosocial service modality in addition to pharmacotherapy. In order of decreasing frequency, these were therapy with a psychologist, self-help group, therapy with a social worker, and therapy with another type of provider. Bipolar patients with personality disorders (80% vs 20%, p = 0.0002), alcohol/drug abuse disorders (76% vs 24%, p = 0.0022), and anxiety disorders (60% vs 40%, p = 0.0043) received more psychosocial services than those without. Poorer global functioning also increased the likelihood of receiving services, whereas being married decreased service utilization. CONCLUSION: Psychosocial service utilization by outpatients with bipolar disorder is strongly linked to greater severity/complexity of illness. Potential moderators, such as insurance status and availability of care, should be examined in future studies.

Adolescent↗

Measuring changes in symptoms relevant to borderline personality disorder following short-term treatment across partial hospital and intensive outpatient levels of care.

OBJECTIVE: This study examined whether measurable changes in symptoms relevant to borderline personality disorder (BPD) occur following short-term treatment across partial hospital and intensive outpatient levels of care. Preliminary data on symptom changes among patients with BPD during the first 3 months of treatment in a step-down treatment program are presented. METHODS: Of the 42 patients who entered the BPD-specific treatment program during the 18-month study period, 36 consented to participate in the study. Patients began treatment in the partial hospitalization program (where the average length of stay is 8 weeks) and then transitioned into the intensive outpatient program. Patients completed questionnaire packets upon admission, and again at 1 month and 3 months into treatment. The questionnaires assessed BPD-relevant behaviors and symptoms, including: mood and emotion dysregulation, parasuicidality, symptom severity, and quality of life. RESULTS: Results indicate significant and progressive improvements in mood and emotion dysregulation, parasuicidality, and symptom severity following 1 and 3 months of treatment. However, neither global functioning nor quality of life dramatically improved. CONCLUSIONS: The findings from this study highlight the amenability of BPD-relevant symptoms to short-term treatments and demonstrate the possibility of measuring change in these symptoms within the very early phases of treatment.

Adolescent↗

A comparison of cognitive-behavioral therapy, sertraline, and their combination for adolescent depression.

OBJECTIVE: To evaluate cognitive-behavioral therapy, antidepressant medication alone, and combined CBT and antidepressant medication in the treatment of depressive disorders in adolescents. METHOD: Seventy-three adolescents (ages 12-18 years) with a primary diagnosis of DSM-IV major depressive disorder, dysthymic disorder, or depressive disorder not otherwise specified were randomly allocated to one of three treatments. Treatment outcome measures were administered before and after acute treatment, and at a 6-month follow-up. Depression diagnosis was the primary outcome measure; secondary measures were self- and other report and clinician rating of global functioning. The trial was conducted at three community-based clinics between July 2000 and December 2002. Data analyses used an intent-to-treat strategy. RESULTS: Following acute treatment, all treatment groups demonstrated statistically significant improvement on outcome measures (depressive diagnosis, Reynolds Adolescent Depression Scale, Revised Children's Manifest Anxiety Scale, Suicidal Ideation Questionnaire), and improvement was maintained at follow-up. Combined cognitive-behavioral therapy and antidepressant medication was not found to be superior to either treatment alone. Compared with antidepressant medication alone, participants receiving cognitive-behavioral therapy alone demonstrated a superior acute treatment response (odds ratio = 6.86; 95% confidence interval 1.12-41.82). Although cognitive-behavioral therapy was found to be superior to antidepressant medication alone for the acute treatment of mild to moderate depression among youth, this may have stemmed from the relatively low dose of sertraline used. CONCLUSIONS: All treatments led to a reduction in depression, but the advantages of a combined approach were not evident.

Adolescent↗

Neurocognition as a stable endophenotype in bipolar disorder and schizophrenia.

Linkage and association studies have paid increasing attention to neurocognition as a putative endophenotype. However, there exists little documentation of its trait stability in schizophrenia or bipolar disorder. Our aim was to determine the longitudinal stability of neurocognitive performance in bipolar versus schizophrenia probands. We administered a neurocognitive battery at two time points, approximately 5 years apart, in 16 schizophrenia and 16 bipolar disorder age-matched subjects. There were no significant changes over time on variables including education, estimated IQ, depression, psychosis, global functioning, or medication status. Schizophrenia subjects showed significant deterioration in one measure of executive functioning but no significant changes in seven of eight other domains. Bipolar patients showed stability over time in attentional measures but greater variability in other domains. These preliminary findings suggest that neurocognitive domains appear longitudinally stable across broad domains in schizophrenia. In contrast, stable functioning may be more limited to attentional domains in bipolar disorder.

Adult↗

The neuronal basis for consciousness.

Attempting to understand how the brain, as a whole, might be organized seems, for the first time, to be a serious topic of inquiry. One aspect of its neuronal organization that seems particularly central to global function is the rich thalamocortical interconnectivity, and most particularly the reciprocal nature of the thalamocortical neuronal loop function. Moreover, the interaction between the specific and non-specific thalamic loops suggests that rather than a gate into the brain, the thalamus represents a hub from which any site in the cortex can communicate with any other such site or sites. The goal of this paper is to explore the basic assumption that large-scale, temporal coincidence of specific and non-specific thalamic activity generates the functional states that characterize human cognition.

Animals↗

Improving search algorithms by using intelligent coordinates.

We consider algorithms that maximize a global function G in a distributed manner, using a different adaptive computational agent to set each variable of the underlying space. Each agent eta is self-interested; it sets its variable to maximize its own function g(eta). Three factors govern such a distributed algorithm's performance, related to exploration/exploitation, game theory, and machine learning. We demonstrate how to exploit all three factors by modifying a search algorithm's exploration stage: rather than random exploration, each coordinate of the search space is now controlled by a separate machine-learning-based "player" engaged in a noncooperative game. Experiments demonstrate that this modification improves simulated annealing (SA) by up to an order of magnitude for bin packing and for a model of an economic process run over an underlying network. These experiments also reveal interesting small-world phenomena.

Journal Article↗

Beta-adrenoceptor blockade and atrio-ventricular conduction in dogs. Role of intrinsic sympathomimetic activity.

1 Atrio-ventricular conduction and its modifications induced by six beta-adrenoceptor blocking agents and isoprenaline have been investigated in the anaesthetized dog using the extrastimulus technique and measuring atrial (AERP), nodal (NERP), global (GERP) effective refractory periods as well as global functional refractory period (GFRP). 2 When beta-adrenoceptor blockade was produced by (+/-)-propranolol (beta 1 + beta 2-adrenoceptor blockade) which is devoid of intrinsic sympathomimetic activity (ISA) but has membrane stabilizing effects (MSE), sotalol (beta 1 + beta 2-adrenoceptor blockade, no ISA, no MSE) and atenolol (beta 1-adrenoceptor blockade, no ISA, no MSE), all parameters were significantly increased. When beta-adrenoceptor blockade was achieved with pindolol (beta 1 + beta 2-adrenoceptor blockade) and practolol (beta 1-adrenoceptor blockade) which have ISA but no MSE, all parameters remained unchanged, as was also the case with (+)-propranolol, which has MSE but neither ISA nor beta-adrenolytic properties. 3 Isoprenaline at high doses significantly reduced the refractory periods but when infusion was stopped, marked but reversible conduction depression was observed. 4 It thus appears that beta-adrenoceptor blockade but not MSE is responsible for the onset of atrial and AV-conduction impairment and that ISA affords protection against this impairment.

Adrenergic beta-Antagonists↗

Effect of thyroid stimulating hormone on adaptive behaviour in Down's syndrome.

Patients with Down's syndrome are particularly vulnerable to the development of both hypothyroidism and Alzheimer's disease. Both hypothyroidism and Alzheimer's disease may be associated with elevated serum concentrations of thyroid stimulating hormone. In a group of institutionalized Down's syndrome patients with normal thyroid function, global scores of ability were higher than in a group of patients with elevated thyroid stimulating hormone levels in the presence of normal T3 and T4. The actual concentrations of thyroid stimulating hormone were shown to be significantly and inversely correlated with scores of global abilities. If these findings are reproducible, the authors believe that thyroid stimulating hormone estimation may provide confirmatory evidence of clinical dementia in this group of mentally handicapped individuals.

Adaptation, Psychological↗

Atrioventricular plane displacement in severe congestive heart failure following dilated cardiomyopathy or myocardial infarction.

Echocardiographic recording of the atrioventricular (AV) plane displacement during the cardiac cycle was used to assess left ventricular (LV) global function in patients with congestive heart failure (CHF). The study population consisted of 70 patients with chronic CHF (NYHA functional groups III and IV) following dilated cardiomyopathy (DCM) or myocardial infarction (MI), and 35 age-matched healthy subjects. The AV plane displacement was recorded from the apical 4- and 2-chamber views at four LV sites located about 90 degrees apart and representing the septal, anterior, lateral and posterior parts of the LV wall. A mean value was calculated from the above sites (AV-mean). Patients with CHF showed a significant generalized reduction of AV plane displacement compared to healthy subjects (5.6 mm vs. 14.5 mm, P less than 0.001). Thirty CHF patients also underwent radionuclide angiography in order to determine the ejection fraction (EF). The correlation between AV-mean and EF was good (r = 0.82, P less than 0.001). The selection of an AV-mean of less than 7 mm to define a severely depressed LV function (EF less than 30%) gave a sensitivity of 92% and a specificity of 67%. It is concluded that the AV plane displacement can be used to estimate LV systolic function in patients with CHF.

Cardiomyopathy, Dilated↗

New developmental insights from high-throughput biological analysis in Caenorhabditis elegans.

The use of Caenorhabditis elegans as a model system for understanding animal development and human disease has long been recognized as an efficient tool of discovery. Recent developments, particularly in our understanding of RNA-mediated interference and its ability to modify gene activity, have facilitated the use of C. elegans in determining gene function via high-throughput analysis. These new strategies have provided a framework that allows investigators to analyse gene function globally at the genomic level and will likely become a prototypic model for biological analysis in the post-genome era.

Animals↗

Persistence of chronic mood disorders: a 2 year follow-up.

Chronic mood disorder patients who remain frequent and long-term users of psychiatric facilities constitute a major clinical concern today. A 2 year naturalistic prospective follow-up study was conducted on a cohort (n = 40) randomly extracted out of 335 such patients. Longitudinal data involving semi-structured interviews, observer-rated scales and self-report measures were available for 37 patients (93%). While three (8%) remitted completely, the cohort on the average showed no statistically significant change in the severity of depression, social adjustment or global functions during the 2 years under observation. Two baseline features that characterized ameliorated patients were the absence of panic disorder and lower level of education.

Adult↗

Galantamine--a novel cholinergic drug with a unique dual mode of action for the treatment of patients with Alzheimer's disease.

Galantamine hydrobromide is a tertiary alkaloid drug that has been developed and approved in a number of countries including the USA and several countries in Europe as a treatment for mild-to-moderate Alzheimer's disease (AD). Galantamine has a unique, dual mode of action. It is a reversible, competitive inhibitor of acetylcholinesterase (AChE), and is the only drug actively marketed for the treatment of AD with proven activity as an allosteric modulator of nicotinic acetylcholine receptors (nAChRs). This latter activity is thought to be particularly important since decreases in the expression and activity of nAChRs make a large contribution to the reduction in central cholinergic neurotransmission in patients with AD. Galantamine exhibits favorable pharmacokinetic characteristics including predictable linear elimination kinetics at the recommended maintenance doses (16 and 24 mg/day), a relatively short half-life (approximately 7 h) and high bioavailability. It is extensively metabolized in numerous pathways, mainly in the liver via cytochrome P450 enzymes CYP2D6 and CYP3A4, and has a low potential for clinically significant drug-drug interactions. During four large randomized, double-blind, placebo-controlled trials of up to 6 months duration, galantamine 16 and 24 mg/day significantly benefited cognitive and global function, ability to perform activities of daily living (ADL) and behavior, relative to placebo and baseline, for up to 6 months. Caregiver burden (time spent by caregivers supervising patients or assisting them with ADL), and caregiver distress (related to patients' behavioral symptoms) were also reduced. Cognitive and functional abilities were preserved at or near baseline for at least 12 months in patients who received galantamine 24 mg/day for 12 months in a long-term US study. These benefits were maximized by early and continued galantamine treatment and, again, were associated with significant reductions in caregiver burden. Trials of the efficacy of galantamine in dementia related to cerebrovascular disease have also yielded positive results. There are no safety concerns associated with the use of galantamine. The incidence of adverse events, particularly cholinergically mediated events affecting the gastrointestinal system, is generally low and can be minimized using the recommended slow dose-escalation scheme. Galantamine may, therefore, help to reduce the overall burden and cost involved in caring for dementia patients. Taking all evidence into account, galantamine has the potential to become a first-line therapy for dementia.

Alzheimer Disease↗

Felbamate in the treatment of Lennox-Gastaut syndrome: results of a 12-month open-label study following a randomized clinical trial.

Felbamate (FBM) is a new antiepileptic drug (AED) that has been evaluated in partial seizures and in the Lennox-Gastaut syndrome (LGS). When tested against placebo in an add-on, randomized, double-blind trial in 73 children with LGS, FBM significantly reduced the frequencies of astatic (atonic) seizures and generalized tonic-clonic seizures plus total seizure counts. In addition, FBM-treated subjects improved significantly on a parent-rated global evaluation and had fewer injuries. Overall, approximately 50% of subjects experienced a 50% or greater reduction in total seizure frequency and a dose-response relationship was apparent. The improvement that occurred in the double-blind study has been sustained for at least 12 months in subsequent open-label follow-up studies. In the first month of FBM treatment, 62% of the subjects who had previously received placebo had a reduction in total seizure frequency of > 50%. By the 12-month follow-up point, approximately half of the patients had a 50% reduction in total seizure count. Astatic seizures responded even better, with two-thirds of patients having a reduction of > 50% in astatic seizure frequency after 12 months of treatment. Based on adverse experience reports thus far, FBM appears to be well tolerated. FBM is the first drug to be shown effective in the LGS in randomized controlled trials. Although few subjects with LGS became seizure free, the frequency of the most severe seizure types decreased and the patients' global functioning improved.

Anticonvulsants↗

A double-blind, placebo-controlled, multicenter study of Cerebrolysin for Alzheimer's disease.

OBJECTIVE: To assess the efficacy and safety of Cerebrolysin over 4 weeks in patients with probable Alzheimer's disease (AD). DESIGN: A 4-week randomized, double-blind, placebo-controlled, multicenter clinical trial. An unequal (Cerebrolysin:placebo = 2:1) randomization was used to assign more patients to the treatment group. SETTINGS: University medical centers and community geriatric hospitals in Korea. PARTICIPANTS: Fifty-three men and women at least 50 years of age admitted to hospitals with mild to moderate AD and otherwise in good health. INTERVENTION: The treatment group (n = 34) received Cerebrolysin (30 mL Cerebrolysin in 100 mL physiologic saline IV) once a day from Monday to Friday for 4 weeks. The control group (n = 19) received placebo. MEASUREMENTS: Primary outcome measures were the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) and the Clinical Global Impression of Severity/ Change (CGIS/C). Secondary outcome measures included Mini-Mental State Examination (MMSE), Geriatric Depression Scale (GDS), Katz Index of Activities of Daily Living (ADL), and Lawton Instrumental Activities of Daily Living (IADL) Scale. RESULTS: After 4 weeks of treatment, Cerebrolysin-treated patients demonstrated significant improvements in the ADAS-Cog (P = .02), CGIS/C (P = .01), and MMSE (P = .04) compared with placebo-treated patients. Among Cerebrolysin-treated patients, 82%, 62%, and 44% were rated improved on ADAS-Cog, CGIS/C, and MMSE, respectively, compared with 31.6%, 22%, and 17% of placebo-treated patients, respectively. However, there were no significant improvements in the Cerebrolysin group compared with the placebo group on the GDS, ADL, and IADL. There were no dropouts in either groups, with 100% compliance to Cerebrolysin and placebo. Only one patient reported a febrile sensation, which was transient and mild in severity. CONCLUSIONS: This study indicates that Cerebrolysin is a safe drug that improves the cognitive deficits and global function in patients with mild to moderate AD. Long-term efficacy and safety of Cerebrolysin in Alzheimer's patients should be evaluated in the future.

Activities of Daily Living↗

Galantamine maintains ability to perform activities of daily living in patients with Alzheimer's disease.

OBJECTIVES: To examine the effect of galantamine on activities of daily living (ADLs) with respect to baseline dementia severity, correlation with cognitive and global function, specific ADLs affected, and maintenance of ADL independence. DESIGN: Secondary analysis of a 5-month randomized, placebo-controlled trial. SETTING: Multiple U.S. clinical centers. PARTICIPANTS: Six hundred fifty-nine patients with mild to moderate Alzheimer's disease (AD) who completed 5 months of treatment. INTERVENTION: Galantamine at a maintenance dose of 16 or 24 mg/d. MEASUREMENTS: The AD Cooperative Study ADL Inventory (ADCS/ADL). RESULTS: Galantamine resulted in more improvement in ADCS/ADL scores than placebo regardless of baseline dementia severity, with the greatest differences occurring in patients with more severe disease. Changes in ADCS/ADL scores correlated significantly with change scores on the cognitive subscale of the AD Assessment Scale (r=-0.24). Galantamine treatment resulted in maintenance or improvement of basic and instrumental ADLs, and change from baseline to Month 5 in scores for each individual ADL item favored galantamine over placebo in three of six basic ADLs and six of 17 instrumental ADLs. CONCLUSION: Galantamine has a favorable effect on ADL performance in patients with AD, detectable after 5 months of treatment, regardless of dementia severity. The ADCS/ADL appears to better measure distinct abilities that may be relevant not only in clinical trials but also in individual patients than do cognitive assessments.

Activities of Daily Living↗