The headache under-response to treatment (HURT) questionnaire, an outcome measure to guide follow-up in primary care: development, psychometric evaluation and assessment of utility.

BACKGROUND: Headache disorders are both common and burdensome but, given the many people affected, provision of health care to all is challenging. Structured headache services based in primary care are the most efficient, equitable and cost-effective solution but place responsibility for managing most patients on health-care providers with limited training in headache care. The development of practical management aids for primary care is therefore a purpose of the Global Campaign against Headache. This manuscript presents an outcome measure, the Headache Under-Response to Treatment (HURT) questionnaire, describing its purpose, development, psychometric evaluation and assessment for clinical utility. The objective was a simple-to-use instrument that would both assess outcome and provide guidance to improving outcome, having utility across the range of headache disorders, across clinical settings and across countries and cultures. METHODS: After literature review, an expert consensus group drawn from all six world regions formulated HURT through item development and item reduction using item-response theory. Using the American Migraine Prevalence and Prevention Study's general-population respondent panel, two mailed surveys assessed the psychometric properties of HURT, comparing it with other instruments as external validators. Reliability was assessed in patients in two culturally-contrasting clinical settings: headache specialist centres in Europe (n = 159) and primary-care centres in Saudi Arabia (n = 40). Clinical utility was assessed in similar settings (Europe n = 201; Saudi Arabia n = 342). RESULTS: The final instrument, an 8-item self-administered questionnaire, addressed headache frequency, disability, medication use and effect, patients' perceptions of headache "control" and their understanding of their diagnoses. Psychometric evaluation revealed a two-factor model (headache frequency, disability and medication use; and medication efficacy and headache control), with scale properties apparently stable across disorders and correlating well and in the expected directions with external validators. The literature review found few instruments linking assessment to clinical advice or suggested actions: HURT appeared to fill this gap. In European specialist care, it showed utility as an outcome measure across headache disorders. In Saudi Arabian primary care, HURT (translated into Arabic) was reliable and responsive to clinical change. CONCLUSIONS: With demonstrated validity and clinical utility across disorders, cultures and settings, HURT is available for clinical and research purposes.

[Trends, Achievements And Prospects Of Biotechnology In The Food Industry].

The article provides analytical screening of biotechnological facilities in the food industry. Presents the basic areas of application of biotechnology research and development, described the feasibility and relevance of the use of genetic engineering, specialized strains of microorganisms and enzyme preparations in the production of food products with functional directivity highest level of quality and safety. Are formulated the most important requirements and selection criteria for the biotechnological component for the various areas of the food industry. Summarizes the scientific achievements of biotechnology and genetic engineering, which promote the development of innovation in creating products for a healthy diet, make it possible to realize the potential of of this direction.

Efficacy assessment of phenobarbital in epilepsy: a large community-based intervention trial in rural China.

BACKGROUND: Many people with epilepsy need not experience further seizures if the diagnosis and treatment are correct. Most epilepsy patients have convulsions, which are usually fairly easy to diagnose. This study tested a model for treatment of people with convulsive forms of epilepsy at primary health-care level in rural areas of China. METHODS: Patients with convulsive epilepsy were identified at primary care level and provided with phenobarbital monotherapy. Local physicians, who were provided with special training, carried out screening, treatment, and follow-up. A local neurologist confirmed the diagnoses. Efficacy was assessed from the percentage reduction in seizure frequency from baseline and the retention of patients on treatment. FINDINGS: The study enrolled 2455 patients. In 68% of patients who completed 12 months' treatment, seizure frequency was decreased by at least 50%, and a third of patients were seizure free. 72% of patients who completed 24 months' treatment had reduction of seizure frequency of at least 50% and a quarter of patients remained seizure free. Probability of retention was 0.84 at 1 year, and 0.76 at 2 years. Medication was well tolerated and reported adverse events were mild; only 32 patients (1%) discontinued medication because of side-effects. INTERPRETATION: This pragmatic study confirmed that this simple protocol was suitable for the treatment of convulsive forms of epilepsy in rural areas of China. Physicians with basic training could treat epilepsy patients with phenobarbital, with beneficial effects for most patients with convulsive seizures. Few cognitive or behavioural adverse events were noted, but formal psychometric testing was not done.

Prevalence of epilepsy its treatment gap and knowledge, attitude and practice of its population in sub-urban Senegal an ILAE/IBE/WHO study.

A door-to-door survey was used to determine the prevalence of epilepsy among 4500 people within the Pikine Health District (population 480,000) Senegal. Prevalence was 14.2/1000, and 23.4% of all people with epilepsy had never received appropriate treatment. Figures for the prevalence had increased since a previous survey in 1989. In parallel a study of knowledge attitude and practice was performed in the same district. Salient findings were that: two-thirds of interviewees had at some time witnessed a seizure, 51% agreed when asked if epilepsy is caused by evil spirits, 35% said epilepsy is contagious, only about 18% said that traditional therapy is best, 60% would not mind their child to play with a child with epilepsy but only 32% would agree if their child would want to marry a person with epilepsy.

Mechanisms of stabilization of biomembranes by alpha-tocopherol. The role of the hydrocarbon chain in the inhibition of lipid peroxidation.

The effects of alpha-tocopherol and its homologues with different chain lengths (6-hydroxy-chromanes: C1, C6, C11) on lipid peroxidation in natural membranes (liver microsomes and mitochondria, brain synaptosomes) and liposomes were studied. It was shown that the antioxidant activity of alpha-tocopherol homologues decreased in the order: C1 greater than C6 greater than C11 greater than alpha-tocopherol (C16). Using fluorescent measurements, the possible reasons underlying these differences were investigated: (i) the distribution between the aqueous media and nonpolar phase of the membrane, which predetermines the binding of alpha-tocopherol homologues to membranes; (ii) the incorporation of alpha-tocopherol homologues into lipid bilayer; (iii) non-uniform distribution (formation of the clusters) of tocopherol homologues in the lipid bilayer; and (iv) transbilayer mobility of alpha-tocopherol homologues and accessibility of the inhibitors for radical-generating centres under enzymically and non-enzymically induced lipid peroxidation. It was demonstrated that: (i) binding of C1 with membranes was less efficient than that of longer-chain homologues (C6, C11, C16); (ii) the level of incorporation of alpha-tocopherol homologues into membranes decreased in a succession alpha-tocopherol C11 greater than C6 greater than C1; (iii) all alpha-tocopherol homologues existed in the lipid bilayer not only in a monomeric form but also associated in clusters thus decreasing the efficiency of radical scavenging; (iv) the short-chain alpha-tocopherol homologue, C1, exhibited a high transbilayer mobility whereas the long-chain one, C16, underwent no transbilayer migration within tens of minutes. The inhibiting effect of alpha-tocopherol esters and C1-acetate was predetermined by their hydrolysis in biomembranes; a strong correlation exists between the rate of the ester hydrolysis and their antioxidant activity in the membrane. In liposomes, in which the esterase activity was absent, alpha-tocopherol esters and C1-acetate exhibited very low lipid peroxidation inhibition.

Stability of exploratory eye movements as a marker of schizophrenia--a WHO multi-center study. World Health Organization.

The exploratory eye movements of patients with schizophrenia reportedly differ from those of patients without schizophrenia and healthy controls. In an attempt to determine whether exploratory eye movements provide valid markers for schizophrenia, the present collaborative study was conducted in six countries to analyze the stability of and variation in the following parameters of exploratory eye movements: the number of eye fixations (NEFs) and mean eye scanning length (MESL) in a retention task; the cognitive search score (CSS) that indicates how frequently the eye focused on each important area of a figure in order to recognize it in a comparison task; and the responsive search score (RSS), which reflects the frequency of eye fixations on each section of a figure in response to questioning in a comparison task. In addition, we investigated the validity of the currently employed discriminant function to extract a common feature of schizophrenia by applying it to the findings of the present study. The exploratory eye movements of 145 patients with schizophrenia, 116 depressed patients and 124 healthy controls at seven WHO collaborative centers in six countries were measured using eye mark recorders during viewing of stationary S-shaped figures in two sequential tasks. The RSSs of patients with schizophrenia were found to be significantly lower than those of depressed patients or healthy controls irrespective of geographical location, with no significant difference existing between the RSSs for depressed patients and those for healthy controls. By inserting the RSS and NEF data for each subject into the formula used to calculate discriminant function, patients with schizophrenia could be discriminated from depressed patients and healthy controls with a sensitivity of 89.0% and a specificity of 86.7%. The RSS is an exploratory eye movement parameter that detected schizophrenia irrespective of culture, race and various other subject variables. Furthermore, it is indicative of the stable, significant difference that exists between subjects with and without schizophrenia. The results of discriminant analysis confirm the previously reported validity of discriminant function.

Stabilization of synaptic membranes by alpha-tocopherol against the damaging action of phospholipases. Possible mechanism of biological action of vitamin E.

Using fluorescent and ESR-spin probes, the effects of phospholipases A2, C and D on rat brain synaptosomal membranes were investigated. It was shown that the exposure of synaptosomal membranes to phospholipases A2, C and D results in their depolarization and an increase of the negative surface potential. In the case of phospholipases A2 and C, these changes are associated with a decrease of the microviscosity of the membrane lipid bilayer. alpha-Tocopherol stabilizes synaptosomal membranes against the damaging action of the phospholipases. This stabilization consists in the reconstitution of the transmembrane potential and an increase of microviscosity of the phospholipase-treated membranes. The stabilizing effect of alpha-tocopherol is due to the binding of phospholipid hydrolysis products, but not to the inhibition of phospholipases. The observed stabilization of synaptosomal membranes by alpha-tocopherol is regarded as a possible mechanism of biological action of vitamin E on biomembranes.

Biological studies of schizophrenia in Europe.

The main achievements in the field of genetics, biochemistry, and immunology of schizophrenia in the laboratories of European research centers are surveyed. Despite the rapid development of scientific research techniques and methodology, the abundant hypotheses on the pathogenesis of schizophrenia are riddled with so many contradictory facts that it is impossible to formulate any concrete model of the disease. One factor impeding the progress of biological research in schizophrenia is the inadequate development of standardized clinical descriptions. This is an obstacle to the study of clinical-biological correlates, which are among the principal criteria used to verify the importance of biological parameters chosen for study in the pathogenesis of the disease. A current strategy in the biology of schizophrenia, which may obviate some of those problems, is the discovery and study of biological markers.

The effect of vitamin E addition to acute neuroleptic treatment on the emergence of extrapyramidal side effects in schizophrenic patients: an open label study.

The anti-oxidant vitamin E has been reported to be effective in the treatment of tardive dyskinesia. The present open label study examined the effect of supplemental therapy with vitamin E on acute extrapyramidal symptoms and cell enzymes in patients receiving neuroleptic drugs. Thirty-nine hospitalized schizophrenic patients were randomly assigned to two groups: group 1 (n = 20) was treated with neuroleptics, and group 2 (n = 19) with neuroleptics combined with a fixed dose of vitamin E (600 IU/day), administered for two weeks. All patients were assessed with the Simpson-Angus Rating Scale (Simpson and Angus, 1970) for neuroleptic induced Parkinsonism (NIP), Barnes' Akathisia Scale (Barnes, 1989), and Brief Psychiatric Rating Scale: laboratory parameters included serum creatine kinase (CK) activity, serum glutamate oxaloacetic transaminase (SGOT) and white blood cell count (WBC). The addition of vitamin E to neuroleptic agents was associated with a trend (p = 0.08) towards prevention of the emergence of NIP compared to neuroleptic treatment alone. Addition of vitamin E to neuroleptics may reduce the severity of acute NIP in schizophrenic patients.

The World Health Organization's global initiative on neurology and public health.

In 1993, the World Health Organization launched a global initiative aimed at increasing public and professional awareness of the public health aspects of neurological disorders. The initial phase of this project has been carried out through the organization of a series of symposia on prevalence, severity and costs of neurological disorders including dementia, stroke, epilepsy and headache. The main objective of the next phase of the project is to develop an international educational programme on neurology and public health and to establish a network of training centres in different regions of the world.

Depression and cognitive impairment in the elderly: a multicentre study.

The present study, conducted in collaboration between the Departments of Psychiatry in Swiss Universities and the World Health Organization, had two main goals: to develop assessment methods which could subsequently be used in the Swiss centres in a standard manner; and to make arrangements for continuing collaboration between the centres in Switzerland and the acquisition of new knowledge about the distinctions between depression and cognitive impairment. For this aim, three different groups of elderly patients of either sex were selected during the period of November 1989 to July 1991 for inclusion in the study. The first two groups included the first ten patients of either sex over 60 years of age consecutively contacting the participating institutions and showing depression with or without clinically significant symptoms of cognitive impairment; the control group included patients showing no depression or clinically significant symptoms of cognitive impairment. A total of 125 patients were included in the initial evaluation, 69 of which were reassessed at a seven-month follow up (on average). Each patient was administered a number of clinician-rated or self-report instruments for the assessment of depression, cognitive impairment, disabilities, physical status and onset of disorders. The study has shown that a variety of instruments can be used for the reliable assessment of depression or cognitive impairment in the elderly; but the instruments for the assessment of depression differentiate only poorly between patients with or without cognitive impairment. Because of the importance of identifying both depressed and cognitively impaired patients among the elderly, different assessment instruments targeted at the different symptom clusters need to be administered simultaneously.

[Multiple forms of thrombocyte monoamine oxidase in patients with manic-depressive psychosis and recurrent schizophrenia]. / Mnozhestvennye formy trombotsitarnoi monoaminoksidazy u bol'nykh maniakal'no-depressivnym psikhozom i rekurrentnoi shizofreniei.

The concentrations of different forms of monoamine oxidase (MAO) in platelets of the peripheral blood from healthy subjects (n = 13), patients with recurrent schizophrenia (n = 6) and those with manic depressive psychoses (n = 5) were measured. MAO of platelets of the peripheral blood from the control subjects and patients with the considered diseases consisted of three forms: MAO-1, MAO-2, and MAO-3. Analysis of the values of the specific activity of each of the studied forms failed to show any significant difference between the patients and controls. Comparison of the quantitative distribution of different forms of MAO in both groups revealed no difference between the groups with regard to MAO-2 and MAO-3 and a significant (P less than 0.01) decrease in MAO-1 (5.34 +/- 1.5%) in patients with mental diseases as compared to this parameter (19.0 +/- 6.5%) in the control group.

[Peripheral blood lymphocytes as a biological indicator of physiologic processes in schizophrenia]. / Limfotsity perifericheskoi krovi kak biologicheskii indikator patologicheskikh protsessov pri shizofrenii.

The results of studying the properties of peripheral blood lymphocytes in schizophrenic patients are reviewed. Three parameters are specified in which the patients' lymphocytes differ substantially from those of healthy donors: these are the resistance to osmotic shock and responses of the cells to stimulation with phytohemagglutinin and concanavalin A. It is shown that all the three parameters are controlled by different factors of the schizophrenics' blood serum. Two of them correlate with the clinical manifestations of the disease. It is concluded that the lymphocytes of schizophrenic patients can serve as a biological indicator of the pathophysiological processes taking place in that disease.

[Analysis of subpopulations of peripheral blood T-lymphocytes of schizophrenic patients]. / Analiz subpopuliatsii T-limfotsitov perifericheskoi krovi bol'nykh shizofreniei.

The reaction of lymphocytes to Con A and PHA and combined action of these 2 T-mitogens in the peripheral blood was studied in schizophrenic patients (25 cases) and normal donors (21 cases). It was demonstrated that study of lymphocyte function in the peripheral blood with the aid of the 2 mitogens makes it possible to differentiate more distinctly the lymphocytes of schizophrenic patients and normals. It was established that the lymphocyte subpopulation capable of responding to both mitogens used is 4 times less in schizophrenics than in normal donors. The proportion of cells reacting only to one of these mitogens is significantly higher than in normals. The total content of mitogen-sensitive T-lymphocytes in schizophrenic patients and normal donors is approximately the same and equals about 40% of the whole lymphocyte population in the peripheral blood.

[Role of schizophrenic patients' serum in the altered osmotic resistance of their lymphocytes]. / Rol' syvorotki krovi bol'nykh shizofreniei v izmen ennoí osmoticheskoi rezistentnosti limfotsitov étikh bol'nykh.

The resistance of peripheral blood lymphocytes was estimated in normal subjects and schizophrenic patients with reference to hypoosmotic effects. It was shown that in normal subjects about 20% of the lymphocytes were slightly resistant. In 60% of the schizophrenic patients the fraction of the slightly resistant lymphocytes was found to be sharply lowered. The content of those cells in the blood of patients with different forms of the disease course was different: patients with the periodic form showed the minimal, and patients with continuously progressing form the maximal deviation from normal. Patients with the schubweise form occupied an intermediate place. Incubation of the lymphocytes of the healthy donors in the serum of schizophrenic patients led to selective destruction of the donor' slightly resistant cells. A statistically significant correlation between the destructive capacity of the patients' serum and the lowering of the content of the slightly resistant lymphocytes in those patients was observed.

[Dependence of the peripheral blood lymphocyte reaction of schizophrenia patients to concanavalin A stimulation on the clinical parameters of the pathological process]. / Zavisimost' reaktsii limfotsitov perifericheskoi krovi bol'nykh shizofreniei na stimuliatsiiu konkanavalinom A ot nekotorykh klinicheskikh parametrov patologicheskogo protsessa.

Studies were performed on an equivalent age group of schizophrenic patients and normal donors to detect the lymphocyte reaction of the peripheral blood to concanavalin A stimulation. It was demonstrated, that in the blood of schizophrenic patients, the part of lymphocytes capable of reacting to stimulation, is 2,3 times less than in the group of normals. The studies showed that the capability of cells to react to stimulation does not depend upon the duration of the disease, the duration of the postmanifest or initial periods, but differs in patients with different forms of schizophrenia. A significant negative correlation was demonstrated between the severity of positive disorders and the lymphocyte response to stimulation.

[Effect of schizophrenic patients' serum on the physiological state of lymphocytes under in vitro conditions]. / Deistvie syvorotki bol'nykh shizofreniei na fiziologicheskoe sostoianie limfotsitov v usloviiakh in vitro.

The report is concerned with the action of the serum of schizophrenic patients on the physiological state of lymphocytes in normal donors. It was established that during the early stages of incubation the action of the serum in schizophrenic patients evokes the activation of lymphocytes in normal donors, that is seen in changes of the ultrastructure and adhesive properties of these cells. On the late stages of cultivation the serum of patients destroys 13.4 +/- 5.9% of lymphocytes of normal donors. In remaining population 21% of lymphocytes lose their capability to react to PHA stimulation by an increase of DNA content.

[Hemolytic properties of the lymphocytes of schizophrenia patients]. / Gemoliticheskie svoistva limfotsitov krovi bol'nykh shizofreniei.

The authors studied the cytotoxic activity of the lymphocytes in the peripheral blood of 16 schizophrenic patients and 14 normal donors in respect to autological erythrocytes. It was demonstrated that the hemolytic activity of the lymphocytes of patients was significantly higher, than in the control group. Activated cells possess cytotoxic properties.

[Activation of lipid peroxidation in the bodies of schizophrenic and manic-depressive patients]. / Aktivatsiia perekisnogo okisleniia lipidov v organizme bol'nykh shizofreniei i maniakal'no-depressivnym psikhozom.

The intensity of lipid peroxidation was studied in schizophrenic and manic-depressive patients. Peroxidation was found to be activated in these diseases as assessed by the content of peroxidation products in the lipid fraction of blood plasma. Manic-depressive patients showed a significant decrease in the intensity of peroxidation processes with improvement in the clinical symptoms of the disease.

[Role of serum factors in decreasing the reaction of peripheral blood lymphocytes in schizophrenia to PHA stimulation]. / Rol' syvorotochnykh faktorov v snizhenii reaktsii limfotsitov perifericheskoi krovi bol'nykh shizofreniei na stimuliatsiiu FGA.

The blood serum of schizophrenic patients and three of its studied fractions (gamma-globulins and remaining after elimination of gamma-globulins and ultrafiltrate protein fractions) inhibit the lymphocyte response of normals to PHA stimulation (an increase of the DNA content in cells). An insignificant inhibitor effect in the blood serum of normals was seen only in the protein fraction. The PHA precipitating activity of the blood serum in schizophrenic patients which is mainly connected with its protein fraction is increased by 30%. However, there are no correlations between this blood serum activity and its capability to inhibit the response of lymphocytes to PHA stimulation.