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[Lipid lowering after percutaneous coronary intervention. Intended and achieved treatment goals in real life].

BACKGROUND: Dyslipidemia is associated with development and progression of coronary artery disease. Especially patients after coronary revascularization benefit by treatment with lipid-lowering drugs. Guidelines for lipid-lowering therapy in patients with or without coronary artery disease recommend treatment goals of lipid levels. However, relevant discrepancies between evidence-based goals and achieved lipid levels in "real life" are reported in large studies. METHODS AND RESULTS: In this study the dynamics of lipid levels (total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides) and of lipid-lowering drugs were analyzed over a 5.5-month period in patients undergoing percutaneous coronary intervention. At the time of coronary intervention only 49.8% of patients were on lipid-lowering drugs, during follow-up dosage was modified only in exceptional cases. Although 87.5% of patients were treated at the time of follow-up, guideline-oriented lipid levels were achieved only in 32.5% of patients after 5.5 months. CONCLUSION: In a high-risk patient population after coronary revascularization, an ineffective treatment of hypercholesterolemia was found. A major problem is the lack of dosage modification of lipid-lowering drugs after initiation. By closer cooperation between hospital and general practitioner lipid-lowering treatment will be optimized and the rate of cardiovascular events will be decreased over long-term follow-up.

Aged↗

Goal-directed fluid management reduces vasopressor and catecholamine use in cardiac surgery patients.

OBJECTIVE: We examined whether guiding therapy by an algorithm based on optimizing the global end-diastolic volume index (GEDVI) reduces the need for vasopressor and inotropic support and helps to shorten ICU stay in cardiac surgery patients. DESIGN AND SETTING: Single-center clinical study with a historical control group at an university hospital. PATIENTS: Forty cardiac bypass surgery patients were included prospectively and compared with a control group. INTERVENTIONS: In the goal-directed therapy (GDT) group hemodynamic management was guided by an algorithm based on GEDVI. Hemodynamic goals were: GEDVI above 640 ml/m2, cardiac index above 2.5 l/min/m2, and mean arterial pressure above 70 mmHg. The control group was treated at the discretion of the attending physician based on central venous pressure, mean arterial pressure, and clinical evaluation. RESULTS: In the GDT group duration of catecholamine and vasopressor dependence was shorter (187+/-70 vs. 1458+/-197 min), and fewer vasopressors (0.73+/-0.32 vs. 6.67+/-1.21 mg) and catecholamines (0.01+/-0.01 vs. 0.83+/-0.27mg) were administered. They received more colloids (6918+/-242 vs. 5514+/-171ml). Duration of mechanical ventilation (12.6+/-3.6 vs. 15.4+/4.3 h) and time until achieving status of fit for ICU discharge (25+/-13 vs. 33+/-17h) was shorter in the GDT group. CONCLUSIONS: Guiding therapy by an algorithm based on GEDVI leads to a shortened and reduced need for vasopressors, catecholamines, mechanical ventilation, and ICU therapy in patients undergoing cardiac surgery.

Algorithms↗

Is sparse and distributed the coding goal of simple cells?

The question of why the receptive fields of simple cells in the primary visual cortex are Gabor-like is a crucial one in vision research. Many research efforts (Olshausen and Field 1996, 1997; van Hateren and Ruderman 1998; van Hateren and van der Schaaf 1998) that yield a set of localized, oriented, and bandpass Gabor-like receptive fields believe that sparse and distributed is the coding goal of simple cells. This paper investigates a more general coding strategy that measures equally any departure from normality in the simple cells' responses. That is, we investigate the possibility that highly kurtotic response histograms may result if simple cells explicitly seek, not maximally kurtotic, but rather maximally non-Gaussian response histograms to natural images. It is found that, under this coding strategy, the simulations produce a majority of localized, oriented, bandpass (Gabor-like) receptive fields. Some receptive fields, however, are spatially distributed and show little oriented structure. Nearly all receptive fields, regardless of whether they are Gabor-like or non-Gabor-like, yield highly kurtotic response histograms to natural images. Thus, in seeking maximally non-Gaussian response histograms, receptive fields spontaneously yield highly kurtotic histograms. The presence in our ensemble of nonlocalized, nonoriented receptive fields may be due to the artificial requirement that receptive fields be orthonormal. We conclude that the high kurtoses observed in the response histograms of simple-cell receptive fields to natural images may reflect a property of natural images themselves rather than an explicit coding goal used to structure simple-cell receptive fields.

Action Potentials↗

Gravitational biology within the German Space Program: goals, achievements, and perspectives.

Gravity plays an important role for the evolution, orientation and development of organisms. Most of us, however, tend to overlook its importance because--due to its constant presence from the beginning of evolution some 4 billion years ago--this environmental parameter is almost hardwired into our interpretation of reality. This negligence of gravity is the more surprising as we all have our strong fights with this factor, especially during the very early and again during the late phases of our lives. On the other hand, scientists have been fascinated to observe the effects of gravity especially on plants and microorganisms for more than a hundred years, since Darwin and Sachs demonstrated the role of the root cap for downward growing plants. Different experimental approaches are nowadays available in order to change the influence of gravity and to study the corresponding influences on the physiology of biological systems. With the advent of spaceflight, a long-term nearly nullification of gravity is possible. Utilisation of this so-called "microgravity" condition for research in life sciences thus became an important asset in the space programs of various space agencies around the world. The German Space Life Sciences Program is managed--like all other space programs and activities in Germany--by the German Aerospace Center (DLR) in its role as space agency for Germany. Within the current space program, approved by the German government in May 2001, the overall goal for its life sciences part was defined as to gain scientific knowledge and to disclose new application potential by research under space conditions, especially by utilising the microgravity environment of the International Space Station. Three main scientific fields have been identified in collaboration with the scientific community: integrative human physiology, biotechnological applications of the microgravity environment, and fundamental biology of gravity and radiation responses (i.e., gravitational and radiation biology). In the present contribution, specific goals as well as achievements and perspectives of research in gravitational biology are given. In addition, some information is provided on spaceflight opportunities available.

Animals↗

Assessment of sexual functioning, mental health, and life goals in women with vaginal agenesis.

Vaginal agenesis is a congenital disorder defined by the incomplete formation of the vagina and other reproductive organs, often including the cervix, uterus, and fallopian tubes. For the patient, this frequently means infertility and an underdeveloped vagina with the subsequent difficulty to have vaginal intercourse. The patient with vaginal agenesis and her family then encounter a variety of psychological concerns that must be addressed during diagnosis, including weighing treatment options, managing interventions, and coping with long-term issues following diagnosis and treatment, such as partnership concerns and infertility. In this study, seven patients between the ages of 18 and 34 completed questionnaires assessing demographic information, sexual functioning, mental health, self-esteem, and life goals. Sexual functioning results were highly variable. Participants reported significant emotional reactions at diagnosis as well as anxiety about the disorder, specifically its role in relationships. However, overall, the group showed average levels of mental health and self-esteem. Participants also showed positive coping techniques through conceptualization of life goals.

Adult↗

Analytical goals for rectilinear calibration functions.

Analytical goals for rectilinearity based on within-subject biological variation have not yet been advocated. On the other hand, the statistical tests to evaluate rectilinearity may be too restrictive for clinical purposes. If rectilinearity of the least-squares regression is rejected by the statistical test used, we propose to compare the systematic error introduced using such a regression line as the calibration function, with the allowable total error. Since total error ideally should be less than the within-subject biological coefficient of variation (C.V.Bw) the goal for rectilinearity we propose is that the maximum allowable systematic relative error produced by the calibration function (LoRi) when a lack of rectilinearity really occurs is: LoRi < C.V.Bw -1.96 C.V.M, where C.V.M is the between-run metrological coefficient of variation of the measurement procedure, corresponding to the value of concentration under study.

Algorithms↗

Health-care delivery in Cuba: nursing's role in achievement of the goal of 'Health for All'.

The findings of a study of the delivery of nursing care in noninstitutionalized settings in Cuba are presented. The study investigated factors associated with change in health status and the role of nursing in the community to bring about that change since the time of the 1959 revolution. Recommendations of the World Health Organization's 'Goal of Health For All by the Year 2000' provided guidelines for the study. In the pursuit of Health for All, the World Health Organization specifically called for universal coverage with primary health care to include the following essential elements: education covering the prevention and control of major health problems; adequate food, safe water and nutrition; maternal and child health including family planning; immunization against infectious disease; prevention and control of endemic diseases; and treatment of diseases and injuries. Findings of the study suggest that nursing can play an important role in the delivery of health care that meets the World Health Organization's goal of Health for All through universal coverage of primary health care to the defined population.

Cuba↗

Lithium effects on position learning with exploratory and aversive goal-box conditions.

Under conflict conditions in which reinforcement occurred within mildly aversive white goal-boxes, the chronic administration of lithium chloride (20 meg/l, in drinking water) to rats, while reducing avoidance of the goal boxes, impaired acquisition of an exploration-reinforced position discrimination. These results were interpreted as supporting the concept that lithium salts reduce the individual's reaction to general environmental stimulation--an effect which may account for its therapeutic action in the treatment of manic disorders.

Animals↗

On considering the unintended impact of evaluation: reactive distortions in program goals and activities.

The relationship between program planning and evaluation can be viewed as bidirectional; that is, evaluation methods, procedures, instruments, and criteria not only are determined by, but also influence, program goals and activities. Within the human services context, several factors or sources of reactivity between evaluation and program planning can be identified. These involve (a) quantification of goals and activities, (b) preferences by different audiences for various kinds of evaluation data, (c) values and evaluation criteria, and (d) evaluation requirements and resource availability. Effects of these reactive features are discussed and illustrated with examples drawn from mental health evaluation and accountability practices. It is argued that for evaluation to be a credible and useful practice, evaluators should plan their efforts and assess their own effectiveness within the larger context of human service systems.

Community Mental Health Centers↗

Modelling the acquisition of goal-directed behaviors by populations of neurons.

Recent neurophysiological studies have revealed the patterns of neuronal activity during the acquisition of goal-directed behaviors, both in single cells, and in large populations of neurons. We propose a model which helps three sets of experimental results in the monkey to be understood: (1) activity of single cells vary greatly and only population activities are causally related to behavior. The model shows how a population of stochastic neurons, whose behaviors vary widely, can learn a skilled conditioned movement with only local activity-dependent synaptic changes. (2) typical changes in neuronal activity occur when the rules governing the behavior are changed, i.e. when the relationship between cues and actions to reach a goal changes over time. There are two types of neuronal patterns during changes in reward contingency: a monotonic increasing pattern and a non-monotonic pattern which follows the change in the way the reward is obtained. Units in the model display these two types of change, which correspond to synaptic modifications related to the encoding of the behavioral significance of sensory and motor events. (3) These two patterns of neuronal activity define two populations whose anatomical distributions in the frontal lobe overlap with a gradient organized in the rostro-caudal direction. The model consists of two artificial neural networks, defined by the same set of equations, but which differ in the values of two parameters (P and Q). P defines the adaptive properties of processing units and Q describes the coding of information. The model suggests that a balance in the relative strengths of these parameters distributed along a rostro-caudal gradient can explain the distribution of neuronal types in the frontal lobe of the monkey.

Animals↗

Movement-related cortical potentials preceding sequential and goal-directed finger and arm movements in patients with cerebellar atrophy.

To determine the influence of cerebellar involvement on the preparatory state of the cerebral cortex for voluntary movements, we studied the movement-related cortical potentials (Bereitschaftspotential, BP) preceding sequential and goal-directed finger and arm movements in patients with cerebellar atrophy (CA). The first task (paradigm 1) consisted of a sequential finger movement at a self-paced rate of every 3 sec or longer, in which patients and control subjects pushed rapidly 7 keys on a keyboard in a sequence visually predetermined on a screen. The second task (paradigm 2) consisted of a goal-directed self-paced movement with visual feedback on a screen. In both paradigms, control subjects and patients had distinct movement-related cortical potentials, but peak amplitudes (close to movement onset) were reduced in the patient group (paradigm 2), whereas in the overall analysis the mean amplitude 600-800 msec before movement onset (NS1) was larger in the patient group (paradigms 1 and 2). Accordingly, the difference (NS2) between peak amplitude and NS1 was smaller in the patient group (paradigms 1 and 2). Whereas control subjects' peak amplitude (paradigm 2) and NS2 (paradigm 1) were focused at Cz, this topographical differentiation was abolished in the patient group. The onset of the BP was earlier in the patients than in the control subjects (paradigms 1 and 2). Our results suggest that pathways from the cerebellum to the cortex do play a role in generating movement-related cortical potentials. A strong input from the cerebellum seems to be crucial for the generation of a normal motor potential close to the movement onset, reflecting a specific deficit in patients with CA. Patients with CA may try to compensate for their motor deficits by a longer cortical activation preceding voluntary movements (earlier onset of the BP). The increased NS1 could be the result of larger effort, by which patients try to compensate for their motor deficits as well.

Adult↗

Semi-automated radiotherapy treatment planning with a mathematical model to satisfy treatment goals.

Iterative algorithms can provide a feasible solution, if any exists, to specified treatment goals. Our model subdivides both the patient's cross section into a fine grid of points and the radiation beam into a set of "pencil" rays. The anatomy, treatment machine parameters, dose limits and homogeneity, are all defined. This process of subdivision leads to a large system of linear inequalities with a solution that provides a radiation intensity distribution that will deliver a prescribed dose distribution. The clinical results from two different algorithms will be presented and contrasted. Once the anatomy, treatment, and machine parameters have been entered, the computerized algorithms yield an answer in several minutes. The Cimmino algorithm also allows "weights" or priority assignments of the treatment goals. The resulting solution is biased towards fulfilling the specified doses for the anatomic regions which were given greater weight. It is desirable to have a systematic search of possible treatment alternatives in complex clinical situations, including 3-dimensional radiation therapy treatment planning (RTTP). Our method has been applied to 2-D RTTP, but is equally applicable to 3-D RTTP with minor modifications.

Algorithms↗

Sample size determination for pair-matched case-control studies where the goal is interval estimation of the odds ratio.

Samples sizes are calculated for case-control studies where 1:1 matching has been employed, and where the goal is the interval estimation of the odds ratio. The optimal sample size is defined to be the smallest value for which a 100(1 - alpha)% confidence interval for the log odds ratio will not exceed a specified width 2 delta with specified probability (1 - gamma). This approach is similar in spirit to the power-based approach for sample size determination when significance testing is the goal. Tables of sample sizes are presented for various choices of parameters. We also find considerable disagreement with a published method based on expected numbers of discordant pairs.

Case-Control Studies↗

Cost effectiveness of rosuvastatin in treating patients to low-density lipoprotein cholesterol goals compared with atorvastatin, pravastatin, and simvastatin (a US Analysis of the STELLAR Trial).

Statin therapy decreases low-density lipoprotein cholesterol levels and the risk of coronary heart disease but has a considerable short-term effect on health care budgets. The cost effectiveness of rosuvastatin (Crestor) has been compared with those of atorvastatin, pravastatin, and simvastatin in lowering low-density lipoprotein cholesterol levels and achieving National Cholesterol Education Program Adult Treatment Panel III low-density lipoprotein cholesterol goals. The analysis was conducted from the perspective of health care payers in the United States. Clinical data were obtained from the Statin Therapies for Elevated Lipid Levels Compared Across Doses to Rosuvastatin (STELLAR) trial. Drug costs were based on wholesale acquisition costs. Cost effectiveness was assessed with the net monetary benefit approach and a 1-year time horizon. Rosuvastatin at 10 mg, the recommended starting dose, was the most cost-effective statin over a large range of "willingness-to-pay" values for a unit of clinical effect (i.e., a 1% decrease in low-density lipoprotein cholesterol or a patient achieving the goal).

Adolescent↗

Risk assessment and strategies to achieve lipid goals: lessons from real-world clinical practice.

Coronary heart disease (CHD) risk assessment to establish risk category and appropriate plasma lipid goals as well as achievement of those lipid goals, are important elements of treatment for dyslipidemia in clinical practice. Cases from clinical practice are presented to illustrate risk assessment and treatment in the settings of peripheral arterial disease (PAD) and heterozygous familial hypercholesterolemia (hFH). Patients with PAD are at high risk of CHD and cardiovascular mortality and may require aggressive lipid-lowering therapy irrespective of the degree of hypercholesterolemia at presentation. Risk in patients with hFH is not adequately reflected in population-based risk algorithms. Patients who have hFH should be considered at high risk for developing CHD and given aggressive lipid-modifying therapy, and family screening should be undertaken for additional case finding.

Adult↗

A dynamic model for action understanding and goal-directed imitation.

The understanding of other individuals' actions is a fundamental cognitive skill for all species living in social groups. Recent neurophysiological evidence suggests that an observer may achieve the understanding by mapping visual information onto his own motor repertoire to reproduce the action effect. However, due to differences in embodiment, environmental constraints or motor skills, this mapping very often cannot be direct. In this paper, we present a dynamic network model which represents in its layers the functionality of neurons in different interconnected brain areas known to be involved in action observation/execution tasks. The model aims at substantiating the idea that action understanding is a continuous process which combines sensory evidence, prior task knowledge and a goal-directed matching of action observation and action execution. The model is tested in variations of an imitation task in which an observer with dissimilar embodiment tries to reproduce the perceived or inferred end-state of a grasping-placing sequence. We also propose and test a biologically plausible learning scheme which allows establishing during practice a goal-directed organization of the distributed network. The modeling results are discussed with respect to recent experimental findings in action observation/execution studies.

Action Potentials↗

Are the health Millennium Development Goals appropriate for Eastern Europe and Central Asia?

This article argues that the health-related Millennium Development Goals do not appropriately address the challenges faced by the countries of Eastern Europe and Central Asia. By ignoring adult mortality, their achievement would result in relatively small gains in life expectancy. To achieve greater impact, policies in this region must supplement the classical Millennium Development Goals with indicators of adult health, in particular cardiovascular diseases and external causes of death. In addition, countries, with support from the international community, must improve the quality of vital registration data to enable more accurate estimation of the disease burden.

Adult↗

Fulfilment of patients' goals after thalamic deep brain stimulation: a follow-up study.

Deep brain stimulation (DBS) in the ventrolateral thalamus (VIM) is shown to reduce tremor in essential tremor (ET) and Parkinson's disease (PD). Our aim was to evaluate the results of VIM DBS from the patients' perspective. Sixteen consecutively included patients (8 ET and 8 PD) described their own outcome goals preoperatively and evaluated the fulfillment 1, 6 and 12 months postoperatively. We conclude that the patients could do specific activities that are of importance to them such as eating, drinking and socializing, and perceived either partial or total fulfillment of their goals.

Adult↗