Prevalence of benign prostatic hyperplasia among the adult general population of five Middle Eastern Countries: Results of the SNAPSHOT programme.

OBJECTIVES: To present data on the prevalence of benign prostatic hyperplasia (BPH) in five Middle Eastern countries (Egypt, Turkey, Kuwait, Saudi Arabia, and the United Arab Emirates; the latter three forming a Gulf cluster). SUBJECTS AND METHODS: The SNAPSHOT programme was a multi-country, cross-sectional epidemiological survey conducted by telephone in a random sample of the adult general population. Subjects were considered to have BPH if they fulfilled the screening criteria, based on diagnosis, symptoms, and treatments received in the past 12 months. Current prevalence (last 12 months) was estimated. Association with co-morbidities was investigated via multivariate logistic regressions. Quality of life (QoL) was assessed using the three-level EuroQol five-dimensions questionnaire (EQ-5D-3 L). RESULTS: In total, 5034 of 33,486 subjects enrolled in the SNAPSHOT programme were men aged ≥50 years. In all, 998 of these men fulfilled the BPH screening criteria. The overall prevalence of BPH ranged from 13.84% (95% confidence interval[CI] 12.3-15.4%) in Turkey, to 23.76% (95% CI 21.8-25.6%) in Egypt, and 23.79% (95% CI 21.2-26.3%) in the Gulf cluster. Co-morbidities occurred more frequently in men with BPH compared to the non-BPH population (57% vs 31%; P < 0.001). Principal co-morbidities associated with BPH were cardiovascular, renal, and diabetes mellitus (P < 0.001). The men with BPH reported significantly reduced QoL, with lower EQ-5D-3 L utility values (0.8) compared to the male general population (0.9) aged ≥50 years (P < 0.001). CONCLUSION: The prevalence of BPH in these five Middle Eastern countries ranges from 13.84% to 23.79%. BPH has a negative impact on QoL and is associated with high levels of co-morbid diseases, indicating a need to better understand the management of the disease to reduce the impact on healthcare systems.

The clinical burden of allergic rhinitis in five Middle Eastern countries: results of the SNAPSHOT program.

BACKGROUND: The SNAPSHOT program provides current data on the allergic rhinitis burden in the adult general population of five Middle Eastern countries (Egypt, Turkey, Kuwait, Saudi Arabia and the United Arab Emirates, the latter three grouped into a Gulf cluster). METHODS: A multi-country, cross-sectional, epidemiological program conducted by telephone in a random sample of the adult general population; quotas were defined per country demographics. Subjects were screened for allergic rhinitis using the Score For Allergic Rhinitis questionnaire. Current prevalence (last 12 months) was estimated. Disease severity and control were assessed using the Allergic Rhinitis and its Impact on Asthma classification and Rhinitis Control Assessment Test respectively. Quality of sleep, impact on daily activities and quality of life were measured using the Epworth Sleepiness Scale, Sheehan Disability Scale and EuroQol Five-Dimension questionnaire respectively. Multivariate logistic regression analyses were used to investigate risk factors and co-morbidities. RESULTS: 1808 of 33,486 subjects enrolled in the SNAPSHOT program fulfilled the case definition for allergic rhinitis. Prevalence was 3.6% [95% CI 3.2-4.0%] in Egypt, 6.4% [95% CI 5.9-6.9%] in Turkey and 6.4% [95% CI 6.0-6.9%] in the Gulf cluster. Risk factors identified were country, co-morbid asthma and income. Subjects with allergic rhinitis reported a significantly lower quality of life compared to the general population (p < 0.0001). Overall, 55% of allergic rhinitis subjects were moderate/severe and 33% were uncontrolled. Both these groups reported impaired quality of life and quality of sleep and increased impairment of daily activities compared to mild/well-controlled subjects (p < 0.0001). CONCLUSIONS: Although the observed prevalence of allergic rhinitis in these Middle Eastern countries is low compared to western countries, its burden is considerable. Allergic rhinitis in general, and specifically uncontrolled and severe disease, results in a negative impact on quality of life, quality of sleep and daily activities.

Burden of disease associated with asthma among the adult general population of five Middle Eastern countries: Results of the SNAPSHOT program.

BACKGROUND: Asthma affects millions worldwide resulting in a significant disease burden. However, data on asthma burden from the Middle East is limited. This analysis describes the asthma burden in Egypt, Turkey and a Gulf cluster (Kuwait, Saudi Arabia and United Arab Emirates) as part of the SNAPSHOT program. METHODS: SNAPSHOT was an observational, cross-sectional program carried out by telephone in a random sample of the adult general population of the five above mentioned countries. Quotas were defined per country demographics. Subjects were considered to have asthma if they fulfilled the screening criteria, based on the global Asthma Insights and Reality studies. Data collected included demographics, physician consultations, and asthma control (measured by the Asthma Control Test; ACT). Quality of life was assessed using the EuroQol Five-Dimension questionnaire (EQ-5D); and limitations to daily activities using the modified Sheehan Disability Scale (SDS). RESULTS: 939 subjects answered questions related to asthma burden. Overall, 367 (44.2%) reported uncontrolled asthma (ACT≤19), and reported significantly lower EQ-5D-3L utility values (0.6 ±â€¯0.4) and EQ-VAS scores (60.7 ±â€¯24.2) compared to controlled subjects (0.8 ±â€¯0.3 and 75.3 ±â€¯19.8 respectively) (p < 0.0001). A significantly higher proportion with uncontrolled asthma also reported experiencing impact on activities of daily living compared to subjects with controlled asthma (p < 0.0001). Overall, 355 (37.8%) asthma subjects were followed by a physician. However, most visits were unscheduled (695;78.0%). CONCLUSION: Uncontrolled asthma imposes a significant burden in these Middle Eastern countries resulting in increased frequency of healthcare use, lower quality of life, and a higher impact on daily life compared to controlled asthma.

Adherence to COPD treatment in Turkey and Saudi Arabia: results of the ADCARE study.

BACKGROUND: COPD affects millions of people worldwide. Poor treatment adherence contributes to increased symptom severity, morbidity and mortality. This study was designed to investigate adherence to COPD treatment in Turkey and Saudi Arabia. METHODS: An observational, cross-sectional study in adult COPD patients in Turkey and Saudi Arabia. Through physician-led interviews, data were collected on sociodemographics and disease history, including the impact of COPD on health status using the COPD Assessment Test (CAT); quality of life, using the EuroQol Five-Dimension questionnaire (EQ-5D); and anxiety and depression using the Hospital Anxiety and Depression Scale (HADS). Treatment adherence was measured using the 8-item Morisky Medication Adherence Scale (MMAS-8). Multivariate logistic regression analysis examined the predictors of non-adherence and the impact of adherence on symptom severity. RESULTS: Four hundred and five COPD patients participated: 199 in Turkey and 206 in Saudi Arabia. Overall, 49.2% reported low adherence (MMAS-8 <6). Of those, 74.7% reported high disease impact (CAT >15) compared to 58.4% reporting medium/high adherence (p=0.0008). Patients with low adherence reported a lower mean 3-level EQ-5D utility value (0.54±0.35) compared to those with medium/high adherence (0.64±0.30; p<0.0001). Depression with HADS score 8-10 or >10 was associated with lower adherence (OR 2.50 [95% CI: 1.43-4.39] and 2.43 [95% CI: 1.39-4.25], respectively; p=0.0008). Being a high school/college graduate was associated with better adherence compared with no high school (OR 0.57 [95% CI: 0.33-0.98] and 0.38 [95% CI: 0.15-1.00], respectively; p=0.0310). After adjusting for age, gender, and country, a significant association between treatment adherence (MMAS-8 score ≥6) and lower disease impact (CAT ≤15) was observed (OR 0.56 [95% CI: 0.33-0.95]; p=0.0314). CONCLUSION: Adherence to COPD treatment is poor in Turkey and Saudi Arabia. Non-adherence to treatment is associated with higher disease impact and reduced quality of life. Depression, age, and level of education were independent determinants of adherence.

Prevalence of asthma among the adult general population of five Middle Eastern countries: results of the SNAPSHOT program.

BACKGROUND: Asthma is a common chronic respiratory disease leading to morbidity, mortality and impaired quality of life worldwide. Information on asthma prevalence in the Middle East is fragmented and relatively out-dated. The SNAPSHOT program was conducted to obtain updated information. METHODS: SNAPSHOT is a cross-sectional epidemiological program carried out in five Middle Eastern countries (Egypt, Turkey, Kuwait, Saudi Arabia, and the United Arab Emirates, the latter three grouped into a Gulf cluster) to collect data on asthma, allergic rhinitis, benign prostatic hyperplasia and bipolar disorder. The survey was carried out by telephone in a random sample of the adult general population with quotas defined according to country demographics. The analysis presented in this paper focuses on asthma. Subjects were screened for asthma based on criteria from the global Asthma Insights and Reality studies. Current prevalence (last 12 months) was estimated. Multivariate logistic regression analyses were used to investigate risk factors related to asthma and the association with allergic rhinitis and other co-morbidities. Quality of life was assessed using the three-level EQ-5D questionnaire. RESULTS: 2124 out of the 33,486 subjects enrolled in the SNAPSHOT program fulfilled the criteria for asthma. The adjusted prevalence of asthma ranged from 4.4% [95% CI: 4.0-4.8%] in Turkey, to 6.7% [95% CI: 6.2-7.2%] in Egypt and 7.6% [95% CI: 7.1-8.0%] in the Gulf cluster. Prevalence was higher (p < 0.0001) in women than men and increased with age (p < 0.0001). Co-morbidities occurred more frequently in asthma subjects compared to the non-asthma population (38% vs. 15% p < 0.0001). Subjects with asthma reported a lower (p < 0.0001) EQ-VAS score (68.2 ± 22.9) compared to the general population (78.1 ± 17.5). The risk factors associated with asthma were age, gender, country, and certain co-morbidities, namely respiratory, cardiovascular, gastrointestinal, nervous, and neurological diseases. CONCLUSION: The observed adjusted prevalence of asthma in the Middle East ranges from 4.4% to 7.6%, which is comparatively lower than the reported prevalence in Europe and North America. Asthma has a negative impact on quality of life, and is associated with high levels of co-morbid diseases, indicating a need for physicians to check for co-morbidities and ensure they are managed correctly in all asthma patients.

Vitamin K antagonist treatment in patients with atrial fibrillation and time in therapeutic range in four European countries.

PURPOSE: Patients with atrial fibrillation are at increased risk for stroke and thus require anticoagulant prophylaxis with vitamin K antagonists. However, many such patients fail to achieve target coagulation status. The objective of this study was to evaluate time in the therapeutic range and its relationship to clinical outcomes in patients with nonvalvular atrial fibrillation prescribed a vitamin K antagonist in everyday clinical practice in 4 European countries (France, Germany, Italy and the United Kingdom). METHODS: Data were extracted from the European electronic primary care database, the Longitudinal Patient Database. Included in the analysis were 6250 adult patients for whom data on monitoring of coagulation time and international normalized ratio were available. The time within the therapeutic range was estimated by using the Rosendaal method. Patients spending >70% of time within the therapeutic range were considered to have well-controlled treatment. Data on stroke and bleeding events occurring during the study period were taken from patient records. Stroke risk was calculated by using the CHA2DS2-VASc score (i.e. 2 points for a history of stroke or TIA and age >75 years, and 1 point for age between 65 and 74 years, hypertension, diabetes mellitus, a recent cardiac failure, vascular disease and female sex). FINDINGS: The proportion of patients with poorly controlled treatment varied from 34.6% in the United Kingdom to 55.8% in Germany. The incidence of stroke was 0.5/100 person-years in well-controlled patients, compared with 1.0/100 in poorly controlled patients. After adjustment for stroke risk factors, the odds ratio was 1.38 (95% CI, 0.93-2.06; P = 0.110). The incidence of hemorrhage was 1.1 and 1.3 events/100 person-years, respectively (odds ratio, 0.91 [95% CI, 0.72-1.16]). IMPLICATIONS: Many patients receiving prophylaxis with vitamin K antagonists in everyday community care have poorly controlled anticoagulation treatment with vitamin K antagonists. Their international normalized ratio is frequently outside the therapeutic range, and they are thus exposed to an unnecessary risk of stroke or bleeding complications.

Chronic obstructive pulmonary disease in the adult population within the Middle East and North Africa region: rationale and design of the BREATHE study.

The objective of the BREATHE study was to estimate the regional prevalence of chronic obstructive pulmonary disease (COPD) symptoms within the general population in the Middle East/North Africa (MENA) region and to document risk factors, disease characteristics and management using a standardised methodology. This was an observational population-based survey performed in ten countries in the Middle East and North Africa (Algeria, Egypt, Jordan, Lebanon, Morocco, Saudi Arabia, Syria, Tunisia, Turkey and United Arab Emirates), together with Pakistan. A general population sample of 10,000 subjects ≥ 40 years of age in each country or zone was generated from random telephone numbers. Structured interviews were proposed by telephone. A screening questionnaire was administered to each subject collecting information on respiratory symptoms and smoking habits. Subjects with chronic bronchitis or breathlessness and smoking ≥ 10 pack · years fulfilled the epidemiological definition of COPD ("COPD" population). This population then completed a full disease questionnaire, the COPD Assessment Test (CAT) and a cost-of-disease questionnaire. A randomly selected sample was also assessed by spirometry. In all, 457,258 telephone numbers were generated and contact was established with 210,121 subjects, of whom 65,154 were eligible and 62,086 accepted to participate. The overall response rate was 74.2%. 2,187 (3.5%) subjects fulfilled the criteria for the "COPD" population. Evaluable spirometry data were obtained from 1,847 (14.2%) subjects to whom it was proposed. The BREATHE study has collected a large amount of information on COPD variables from a representative sample of the general population of countries in the MENA region, which can be compared with other regional COPD initiatives.

Psychometric evaluation of the COPD assessment test: data from the BREATHE study in the Middle East and North Africa region.

The objective of this study was to assess the validity and performance of the Arabic and Turkish versions of the COPD Assessment Test (CAT) for evaluating the severity and impact of COPD symptoms. The data were obtained from the BREATHE study in the Middle East and North Africa region, a large general population survey of COPD conducted in ten countries of the region (Algeria, Egypt, Jordan, Lebanon, Morocco, Saudi Arabia, Syria, Tunisia, Turkey and United Arab Emirates), using a standardised methodology. A total of 62,086 subjects were screened, of whom a random sample of 5,681 subjects were administered the CAT by telephone. 5,639 evaluable questionnaires were recovered, representing a completion rate of 99%. In addition, the CAT was administered to an additional 833 subjects fulfilling the epidemiological diagnostic criteria for COPD. Mean scores in the general population were 6.99 ± 6.91 for the Arabic version and 9.88 ± 9.04 for the Turkish version. In patients with COPD, mean scores were 16.2 ± 9.1 and 20.9 ± 10.2 respectively. Scores were consistently higher in smokers than in non-smokers. In the general population, the proportion of respondents fulfilling criteria for COPD rose with higher CAT scores, and particularly above the 80th percentile, where 63% of COPD cases were to be found. This suggests that the CAT may be useful as a case-finding tool in the general population. In the COPD population, healthcare resource consumption rose linearly with CAT score above a threshold score of twenty, arguing in favour of the good criterion validity of the CAT. The internal consistency of the CAT was high (Cronbach's α 0.85 for the Arabic and 0.86 for the Turkish versions) and the factorial structure was unidimensional. In conclusion, this study performed in Arabic and Turkish speaking populations confirms the utility and validity of the CAT as a simple tool to collect data on the severity and impact of COPD symptoms, and suggests that it may potentially be useful as a case-finding tool to identify people at risk for COPD in the general population.

Rate of change in early Huntington's disease: a clinicometric analysis.

Sensitive outcome measures for patients with Huntington's disease (HD) are required for future clinical trials. Longitudinal data were collected from a 3-year study of 379 patients suffering from early HD who were not treated by antipsychotics. Progression of UHDRS item scores was evaluated by linear regression and slope, whereas correlation coefficient, standard error, and P values were estimated on the basis of the data of eight evaluations from screening to study end (36 months). For the functional assessment dimension, the proportion of "no" responses at baseline and at study end was determined. Linear progression was observed for the motor score and for all three functional measures (i.e., functional assessment score, independence assessment score, and total functional capacity score). In contrast, there was little evidence for progression of the behavioral assessment score over the study period, whereas the cognitive assessment score was intermediate. Twenty-two motor-score items showed linear progression, with a slope of >0.003. These included all chorea items, finger tapping and pronation/supination (left and right), gait, tongue protrusion, and tandem walking. Different symptom domains and individual items evolved at different rates in this group of patients suffering from early HD. It may be possible to select sensitive items to create a simplified version of the UHDRS, which would be more efficient and more sensitive for the assessment of disease progression in clinical trials and natural history studies.

The METEOR study: frequency of metabolic disorders in patients with schizophrenia. Focus on first and second generation and level of risk of antipsychotic drugs.

The objective of this crosssectional study was to estimate the prevalence of metabolic disorders and hypertension in patients with schizophrenia and to compare prevalence between patients treated with first-generation (FGA) and second-generation (SGA) antipsychotic drugs. The study included 2270 adults with schizophrenia. Patients were assigned to an FGA or SGA stratum on the basis of current treatment. Data were collected on sociodemographic, lifestyle and clinical variables. Blood pressure, waist and hip circumference, blood glucose, triglycerides and cholesterol were measured. The primary evaluation criterion was the prevalence of a glycaemic disorder. Secondary criteria were the prevalence of dyslipidaemia, obesity, hypertension and metabolic syndrome. A propensity score was used to control imbalance between strata. The prevalence of glycaemic disorders was 31.1% (FGA) and 27.6% (SGA). No between-strata difference in prevalence was observed for glycaemic disorders, dyslipidaemia or metabolic syndrome. The prevalence of hypertension was higher (P=0.033) in the FGA group. The proportion of women (but not men) who were overweight or obese was higher in the SGA group (P=0.035), as was the proportion reporting weight gain of more than 5 kg (P<0.001). In an exploratory unadjusted post-hoc analysis, significantly higher frequencies of dysglycaemia (28.5 vs. 22.0%; P=0.006), low HDL cholesterol (35.3 vs. 29.7%; P=0.023) and metabolic syndrome (36.7 vs. 30.7%; P=0.021) were observed in patients taking SGAs considered to carry high metabolic risk compared with those taking low-risk agents. In conclusion, metabolic disorders are prevalent in patients with schizophrenia treated with antipsychotics and are under-diagnosed and under-treated.

The METEOR study of diabetes and other metabolic disorders in patients with schizophrenia treated with antipsychotic drugs. I. Methodology.

Patients with schizophrenia present a two- to three-fold higher prevalence of diabetes, of metabolic syndrome and of cardiovascular morbidity. The reason for this increased prevalence may involve intrinsic vulnerability, lifestyle factors and iatrogenic effects of antipsychotic drugs. The objective of this multinational, cross-sectional, pharmacoepidemiological study was to determine the prevalence of diabetes, lipid disorders, obesity, hypertension and the metabolic syndrome in patients with schizophrenia treated with antipsychotic drugs. Particular attention was taken to acquire data on a wide a range as possible of demographic, clinical and lifestyle variables that may influence the risk of metabolic disorders, which were taken into account in the calculation of prevalence data by propensity scoring. The study included 2270 subjects from 16 European countries, predominantly from Central and Eastern Europe. The proportion of subjects presenting the pathologies of interest was relatively high, ranging from 28% for glycaemic disorders to 70% for lipid disorders.

The Asthma Insights and Reality in the Maghreb (AIRMAG) study: perspectives and lessons.

Asthma is the most frequently encountered allergic respiratory disease, and one that has a potentially serious impact on patients' functioning and well-being. From a public health perspective, it is important to collect data on the prevalence, burden and management of asthma in order to improve understanding of the pathogenesis of asthma and to ensure that national healthcare policies are adapted and appropriate. In this respect, the different AIR surveys, which have collected standardised data on asthma in the general population of a large number of countries around the world, have made an important contribution. The latest of these surveys is the AIRMAG survey, performed in the three Maghreb countries of Algeria, Morocco and Tunisia. In these countries, the prevalence of asthma (3.4% to 3.9%) is in the low to moderate range. This is consistent with rates observed elsewhere in the Mediterranean basin. Nonetheless, the prevalence of asthma in the Maghreb may be expected to rise in the future as populations become more urbanized and adopt a more 'Westernized' lifestyle. Indeed the prevalence of asthma is already higher in the urban coastal regions of these countries than in the more rural mountainous and desert regions. Asthma control in the Maghreb is relatively poor compared to other regions evaluated in previous AIR studies, with control being unacceptable in around three-quarters of respondents. Although part of the explanation may reside in limited access to care, treatment rates for inhaled corticosteroids (26.1% of adults and 29.1% of children) were no worse than those reported in previous AIR studies. On the other hand, asthma monitoring through regular follow-up visits, home flow-meter use and preparation of individualised asthma management plans was in general unsatisfactory. In addition, awareness of asthma in the general population of the Maghreb countries was low. Education measures directed at the patient, together with programmes directed at the physician to ensure systematic monitoring and the use of a 'treat to target' approach to therapy, could do much to increase quality of life and minimise restrictions on activities in patients with asthma in the Maghreb.

Validation of the Asthma Control Test questionnaire in a North African population.

BACKGROUND: Patient-reported outcome measures are required to measure asthma control. The Asthma Control Test (ACT) is one such measure which was used in the AIRMAG study, a general population study of asthma in the Maghreb. Three dialectal Arabic versions of the ACT (Algerian, Moroccan and Tunisian) were developed. OBJECTIVE: To perform a psychometric evaluation of the properties of dialectal Arabic versions of the ACT used in the AIRMAG study. METHODS: The test data came from 624 adult subjects in a random general population sample in Algeria, Morocco and Tunisia. The internal consistency of the ACT was analysed using Cronbach's a coefficient. The factorial structure was explored by primary component analysis with varimax rotation. Test-retest reproducibility was assessed in a subgroup of 61 subjects. Face and discriminant validity were assessed. RESULTS: Cronbach's a coefficient ranged from 0.58 for the Algerian version to 0.67 for the Moroccan version. The 'use-of-rescue-treatment' item was identified as discordant, since its removal resulted in an increase in Cronbach's a coefficient. The discordance of this item was confirmed by primary component analysis, where the four remaining items were aligned along a single dimension, and the 'use-of-rescue-treatment' item offset along a second dimension. Test and retest scores were well correlated (r =0.704). The ACT showed good face and discriminant validity. CONCLUSIONS: The ACT is a valid measure of asthma control in a North African context, although its internal consistency is compromised by the 'use-of-rescue-treatment' item, probably due to limited access to care and use of short-acting beta-agonists.

Riluzole in Huntington's disease: a 3-year, randomized controlled study.

OBJECTIVE: We conducted a randomized double-blind trial of riluzole in Huntington's disease to investigate the efficacy of this antiexcitotoxic drug in slowing disease progression. METHODS: The study included 537 adult patients with a clinical diagnosis of Huntington's disease confirmed by genotyping. Patients were randomized (2:1) to treatment with riluzole (50mg twice daily) or placebo for 3 years. Concomitant use of antichoreic medication was forbidden, and introduction of such medication was a predefined end point. The primary outcome measure was change in a combined score derived from the motor and total functional capacity subscores of the Unified Huntington's Disease Rating Scale. Safety was also evaluated. RESULTS: A total of 379 patients completed the study (mean age, 47 [standard deviation, 9.5] years; 50% female patients). The principal reason for discontinuation was introduction of antichoreic medication. The median change from baseline in the combined score (primary outcome) for the "per protocol" population was 13.7 (95% confidence interval, 11.1-17.2) in the placebo group and 14.3 (95% confidence interval, 11.7-16.6) in the riluzole group. No intergroup difference in outcome could thus be demonstrated (p = 0.93, Mann-Whitney U test). No differences in secondary efficacy outcome variables were observed except for more frequent recourse to antichoreic medication in the placebo group. No unexpected adverse events were reported, and tolerability was acceptable. INTERPRETATION: No neuroprotective or beneficial symptomatic effects of riluzole in Huntington's disease were demonstrated.

[Tools for assessing patient perception of the impact of migraine]. / Perception de l'impact de la migraine par le patient : les outils de mesure.

Patient-reported outcome, relating to the impact of disease and therapy on the wellbeing of the patient, has become an essential part of medicine, guiding enlightened public health policy and resource attribution. Assessment of patient-reported outcome requires the development of specific and validated instruments, generally questionnaires completed by the patient. In the case of migraine, a number of such specific instruments have been developed to measure severity, associated disability, effects on quality of life and overall impact of headache. In addition, generic quality of life measures have allowed migraine to be compared with other pathologies. For example, using the SF-36 generic health-related quality of life profile, quality of life has been shown to be negatively associated with headache severity, impacted more by migraine headaches than by other forms of episodic headache, and diminished to a similar degree in migraine and in other chronic disorders such as depression. Migraine-specific quality of life measures have also been developed, and these are more sensitive to change than generic measures. An example is the QVM scale that has been used to demonstrate an improvement in quality of life following treatment with a triptan. Moreover, quality of life scores on this measure are inversely related to the economic cost of migraine. Disability associated with migraine can be measured using the MIDAS scale. Disability has been shown to be determined by the frequency and severity of headaches and by the headache syndrome itself, with migraine causing more disability than other forms of episodic headache. The MIDAS scale has been used to develop treatment strategies stratified on the level of disability. The severity of individual headaches can be quantified using the MIGSEV scale. The severity of individual headaches has been shown to be closely associated with overall disability, quality of life and overall healthcare expenditure. Finally, the global impact of headaches is measured using the HIT-6 questionnaire, which discriminates well between different headache types and is again closely related to quality of life. These and other measures of the patient's perception of migraine have allowed an ever more precise picture of this multifacetted disorder to be drawn.

The tolerability of riluzole in the treatment of patients with amyotrophic lateral sclerosis.

Riluzole is the only disease-modifying drug approved for the treatment of amyotrophic lateral sclerosis (ALS), in which it has been demonstrated to extend survival. The overall tolerability of riluzole is good and the drug can be used in all patients with ALS except those with elevated transaminase levels or active liver disease. The most frequently encountered adverse events (AEs) that appear to be attributed to riluzole are asthenia and nausea, observed in 18 and 15% of patients taking riluzole in the randomised clinical trial programme, respectively. These same AEs, albeit at a lower frequency, are also reported in Phase IV observational studies and in pharmacovigilance surveys. No unexpected AE clearly related to riluzole has emerged in the seven years that riluzole has been in extensive use in ALS patients. The most important potential safety issue with riluzole is hepatic impact with elevations of transaminases. Serum alanine aminotransferase levels more than three times the upper limit of normal are observed in 10 - 15% of patients. For this reason, strict monitoring of liver enzymes is recommended in patients with ALS taking riluzole, and treatment is contraindicated in subjects with elevated transaminases before the start of treatment. There is a suspicion that riluzole may, in rare cases, cause neutropenia, and physicians should be vigilant towards this risk.

A Role for Nitric Oxide in Long-term Potentiation.

Nitric oxide production in the cerebellum and induction of long-term potentiation (LTP) in the hippocampus have some characteristics in common: both phenomena are induced by activation of N-methyl-d-aspartate receptors and both are highly dependent on calcium-mediated processes. Here we provide evidence that endogenous nitric oxide production is necessary for synaptic plasticity in the CA1 hippocampus of the rat. LTP recorded in slices was blocked in a concentration-dependent manner by the nitric oxide synthase inhibitors l-NG-nitroarginine and l-NG-nitroarginine methyl ester, but l-NG-monomethylarginine was only marginally active. Bathing the slices with haemoglobin, a protein that scavenges nitric oxide, also resulted in a concentration-dependent blockade of LTP. Nitric oxide released locally from hydroxylamine produced a stable potentiation of synaptic transmission that was not additive with LTP induced by high-frequency stimulation. These results are fully consistent with the presumed retrograde messenger role of nitric oxide in LTP.