Tonabersat, a gap-junction modulator: efficacy and safety in two randomized, placebo-controlled, dose-ranging studies of acute migraine.

Tonabersat is a novel benzopyran derivative that blocks the cortical spreading depression proposed to be associated with migraine attacks. The ability of single oral doses of 15, 25, 40 and 80 mg of tonabersat to relieve the symptoms of moderate to severe migraine was evaluated in 859 migraineurs enrolled in two dose-ranging, double-blind, randomized, placebo-controlled, parallel-group trials, one international and the other North American. In the international study, significantly more patients given tonabersat than given placebo experienced relief of headache pain at 2 h (15 mg, 36.8%; 40 mg, 40.7%), the principal efficacy variable, and at 4 h (40 mg, 63.0%) and complete abolition of headache at 4 h (40 mg, 34.3%). None of the primary or secondary efficacy variables indicated significant differences between tonabersat and placebo in the North American study. Tonabersat was generally well tolerated, with dizziness and nausea the most common side-effects. Serious adverse events were uncommon, and no patient withdrew from either study because of adverse events. These results suggest a possible interplay between tonabersat pharmacokinetics (the relatively long time required to reach maximum plasma concentrations) and patient characteristics (previous triptan exposure) in the management of acute migraine attacks. Based on the pharmacokinetics and actions on cortical spreading depression, tonabersat may have potential value in migraine prophylaxis.

Developing dental education in primary care: the student perspective.

A pilot outreach course in restorative dentistry based in community clinics began in 2001. As part of the evaluation, 48 fourth year students completed a questionnaire about their opinions of the new course, and about restorative dentistry clinics in the dental hospital. Time management was the most frequently mentioned gain from outreach. In relation to the dental school, students most often saw the specialised teaching staff as a gain. Outreach was equally or more important for students' confidence in clinical diagnosis of dental caries, treatment planning, direct restorations, communicating with patients, and managing patients, time, and resources. The dental hospital was equally or more important for their confidence in the diagnosis of periodontal disease, root planing, crowns, bridges, dentures, and communicating effectively with laboratory staff. Patients in outreach were seen as different from those at the dental hospital because they were unselected, and had different treatment needs. Meeting course requirements was the most frequent concern about outreach. In relation to the dental hospital, students were most often concerned about the quality of teaching and support available. Outreach and the dental hospital provided complementary experiences and the new course met its educational objectives.

Sumatriptan nasal spray for the acute treatment of migraine. Results of two clinical studies.

BACKGROUND: Sumatriptan nasal spray may be particularly useful for patients whose nausea and vomiting preclude them from using oral migraine medication or for patients who prefer not to use an injectable migraine medication. The objective of this study was to evaluate in two clinical studies the efficacy and tolerability of the intranasal form of sumatriptan in the acute treatment of a single migraine attack. International Headache Society-diagnosed adult migraineurs in two randomized, double-blind, parallel-group, multicenter studies (n = 409 and 436) used sumatriptan nasal spray 20 mg, 10 mg, or placebo (2:1:1) for the acute treatment of a single migraine attack at home. Predose and at predetermined postdose intervals, patients recorded headache severity (none, mild, moderate, severe); time to meaningful relief; clinical disability (none, mildly impaired, severely impaired, bed rest required); presence/absence of nausea, photophobia, and phonophobia; and the occurrence of adverse events. Two hours postdose in the two studies, moderate or severe baseline pain was reduced to mild or none in 62 to 63% of patients treated with sumatriptan 20 mg, 43 to 54% of patients treated with sumatriptan 10 mg, and 29 to 35% of placebo-treated patients (p < 0.05 20 mg versus placebo for both studies and 10 mg versus placebo for study 1). Onset of relief relative to placebo began as early as 15 minutes postdose (sumatriptan 20 mg, study 2). Clinical disability at 2 hours postdose was reported as mildly impaired or normal in 72 to 74% of patients treated with sumatriptan 20 mg, 56 to 68% of patients treated with sumatriptan 10 mg, and 47 to 58% of placebo-treated patients (p < 0.05 20 mg versus placebo for both studies). Similar efficacy rates were observed for nausea, photophobia, and phonophobia. The most common adverse event in the active treatment groups was disturbance of taste (bad, bitter, or unpleasant taste). Aside from this event, the pattern and incidence of adverse events did not differ among treatment groups. From these results we determined that sumatriptan nasal spray is a rapidly effective, well-tolerated migraine treatment. The 20-mg dose was effective in treating the entire migraine symptom complex, and the 10-mg dose was less consistently effective.

Optimizing the dose of zolmitriptan (Zomig, 311C90) for the acute treatment of migraine. A multicenter, double-blind, placebo-controlled, dose range-finding study. The 017 Clinical Trial Study Group.

This study investigated the efficacy of zolmitriptan (Zomig, formerly 311C90) in acute migraine therapy. Patients with a history of migraine were randomized in a double-blind, multicenter, placebo-controlled, dose range-finding study of oral zolmitriptan 1, 2.5, 5, or 10 mg versus placebo for the treatment of a severe or moderate migraine headache. Patients with persistent or recurrent headache 4 to 24 hours after the initial dose, who did not take escape medication, were eligible to receive a second blinded dose of either zolmitriptan or placebo. Of 1,144 patients treated, 999 evaluable patients completed the study. The headache response rates with zolmitriptan doses > or = 2.5 mg were 44 to 51% at 1 hour, 65 to 67% at 2 hours, and 75 to 78% at 4 hours (all significantly superior to placebo). Also, zolmitriptan effectively relieved migraine-associated symptoms such as nausea, photophobia and phonophobia, and reduced activity impairment. Rates of headache recurrence, headache persistence, and use of escape medication were lower with zolmitriptan doses > or = 2.5 mg than with placebo. In patients with persistent or recurrent headache, a second zolmitriptan dose effectively treated both headache and nonheadache symptoms. Zolmitriptan was well tolerated, with a lower incidence of adverse events being reported with doses < or = 2.5 mg than with those > or = 5 mg. Zolmitriptan is a well tolerated and effective acute migraine therapy providing rapid relief of migraine headache within 1 hour. A clear dose-response relationship between efficacy and tolerability suggests that 2.5 mg is the optimal initial dose for the acute treatment of a migraine attack.

Fiorinal with codeine in the treatment of tension headache--the contribution of components to the combination drug.

The contribution of the Fiorinal and codeine phosphate components to the effectiveness of the Fiorinal with Codeine combination in the treatment of tension headache symptoms was evaluated in a randomized, placebo-controlled, multicenter double-blind study. Patients admitted to the trial took two capsules of Fiorinal with Codeine, Fiorinal alone, codeine alone, or placebo during each of two tension headache attacks. Immediately before and at intervals up to four hours after drug ingestion, patients rated pain severity, pain relief, the tense and uptight feeling, and muscle stiffness. The response to treatment was evaluated in 154 patients. Despite a high placebo response, a factor known to obscure the contribution of components, Fiorinal and codeine were each found to contribute significantly to the therapeutic effect of the Fiorinal with Codeine combination. Statistical or borderline superiority of the combination drug over Fiorinal alone was seen most frequently at the early evaluations, a finding that reflected the rapid onset of action of codeine. Statistically significant differences between Fiorinal with Codeine and codeine alone seen principally at the later assessments reflected the long duration of action of the Fiorinal component. The frequency of adverse reactions did not differ significantly among the four study groups.

A long-term study to maximise migraine relief with zolmitriptan.

Part 1 of this international study was a randomised, double-blind, placebo-controlled study of 2.5 mg and 5 mg zolmitriptan (Zomig) in the treatment of persistent migraine headache, two hours after an initial dose of 2.5 mg zolmitriptan. Part 2 was a non-comparative evaluation of long-term, unrestricted zolmitriptan use for treatment of initial, persistent and recurrent migraine headaches. In Part 1, following the treatment of moderate or severe persistent headache, two-hour headache response rates with 5 mg zolmitriptan (51.6%, n = 322), 2.5 mg zolmitriptan (49.7%, n = 324) and placebo (51.6%, n = 343) were not significantly different. However, the pain-free response rate following the treatment of persistent migraine headache of any intensity was significantly higher with 5 mg zolmitriptan than with placebo (36.0% vs. 25.5%; p < 0.001). This was predominantly due to effects in the subgroup of patients with mild headache. Thus, migraine relief in patients whose initial headache shows a partial response to 2.5 mg zolmitriptan may be maximised by a second 5 mg dose. In Part 2 (involving 2499 evaluable patients), 65.8% of attacks were treated with a single dose of zolmitriptan (2.5 mg or 5 mg). Of those migraine attacks initially treated with 2.5 mg zolmitriptan, 70.3% required no further dose, similarly 62.7% of migraine attacks treated initially with 5 mg zolmitriptan only required a single dose. Over the whole attack (i.e. initial and any persistent headache), headache response rates to one or two zolmitriptan doses were greater than 88.8%. 'Level of pain' was the primary factor influencing the choice of dose. Zolmitriptan provided consistent migraine headache relief in the majority of patients and was well tolerated.

Drug abuse and headache.

Substance abuse has been reported frequently in chronic headache patients. The problem exists in most Western countries. Abuse of various compounds frequently leads to a state of dependency. Prescription as well as over-the-counter agents are often abused. Aspirin, acetaminophen, and caffeine are the most frequently abused compounds. Butalbital, ergot alkaloids, NSAIDS, and narcotic and oral or intranasal sympathomimetics are often abused. Patients with chronic daily headache complain of symptoms that may suggest a mixed-type headache. Features of migraine and muscle contraction headache often coexist in these individuals. It has been suggested that the most frequent cause for the transformation of a periodic headache into a daily headache is substance abuse. Substance abuse and drug dependency have multiple causes, and the etiology will reside with the compounds that are used to excess. The problem may arise as a result of poor instructions from the physician, improper diagnosis with gradual escalation in amounts of drug consumed, or a reinforcement mechanism and a brain stimulation-reward effect. The brain reward system has been studied with narcotics and psychomotor stimulants. It may be activated to a lesser degree with ergotamine, barbiturates, and other abused substances. The long-term effects of substance abuse are contingent on the compounds that are used. They may result in organ damage, medical complications, vascular injury, and a refractory state with chronic headache that eludes successful management of the headache disorder. Patients exhibit a less-than-satisfactory quality of life and are often depressed. Treatment includes outpatient care in cooperative, less dependent patients. Often patients will require inpatient management in order to discontinue use of the abused agents. Pharmacologic agents, behavior modification, psychotherapy, dietary intervention, and acupuncture may be necessary to treat the patient. Each patient must be treated by an interested physician, and the patient will require one or more of the preceding measures for a successful outcome. Often abused compounds must be discontinued in order to obtain a satisfactory response in an individual with chronic headache.

Drug abuse in headache patients.

A significant percentage of chronic headache sufferers use excessive quantities of substances for relief. Drug dependency is frequent in these patients. Patients have an impaired lifestyle, sustain organ system damage, may suffer a withdrawal syndrome, and continue to have headaches. Drug abuse must cease before a satisfactory remission occurs. Particular attention is directed to ergotamine, butalbital, analgesics, and caffeine. The mechanism of substance abuse may be related to repeated use of substances that reinforce behavior and stimulate brain reward systems. Treatment includes comprehensive diagnostic workup, withdrawal of the agent, and use of headache preventives. beta-Adrenergic blockers, tricyclic antidepressants, monoamine oxidase (MAO) inhibitors, and nonsteroidal anti-inflammatory agents may be of value. Behavior modification and dietary counseling are also helpful.

Headache and head trauma.

Headache is a common symptom following head trauma and not related to the degree of trauma. The term post-head-trauma syndrome is used to denote a group of symptoms following head trauma. Dizziness, vertigo, perceptual changes, memory loss, paresthesias, and tinnitus have been reported as well as psychological disturbances. Pathophysiology of headache and other symptoms in the syndrome are believed to relate to vascular and neuronal disturbances. Imaging techniques may provide objective evidence of changes in the brain. Often diagnostic studies do not reveal an abnormality. Treatment consists of diagnosing the type of headache and targeting appropriate therapy. Long-term prognosis is good, the majority of patients recovering after 1 year.

Using metaphor to read the organisation of the NHS. National Health Service.

The paper is concerned with the complexity of the British National Health Service (NHS) as an organisation and with different ways of seeing this. Morgan proposes that explanations of organisational life are based on metaphors which highlight particular interpretations (Morgan, G., 1986, Images of Organisation. London, Sage). The ability to "read" a complex phenomenon depends on being able to see how these different aspects co-exist. The study applies metaphoric thinking to the organisation of the NHS. Utilising documentary data sources, a diagnostic reading is made examining different metaphors to highlight key aspects of the situation. The metaphors of machine and organism are drawn from Morgan's conceptual scheme, those of religion and marketplace are proposed as of particular relevance to the NHS. In the religious metaphor the focus is on the mission of the NHS in terms of its founding principles of universality, comprehensiveness, equality and collectivism. Perceived as a machine the NHS is characterised as an organisation originally based on technocratic rationality and its subsequent history interpreted as moving towards increasingly centralised control. An alternative perspective on the same events is considered in terms of the organic metaphor. In this view the NHS is examined as an open system, which is devolved, decentralised, participative and responsive to its environment. The image of the marketplace focuses on the impact on the organisation of the introduction of competition and incentives in the post-reform period. Other images are sketched briefly. In the critical evaluation the insights generated by the different images are assessed and the different interpretations linked together. It is concluded that metaphoric thinking enables us to appreciate and interpret the ambiguities and paradoxes in NHS organisational life.

Smoking and the female professions: pre-occupational influences on the behaviour of recruits to nursing and teaching.

A questionnaire and interview study of female recruits to nursing and teaching showed that occupational differences in the prevalence of smoking are already established at entry to training. The social characteristics of the smokers in the sample corresponded to those of women smokers generally. Differences in education and social origin contributed to occupational variations in behaviour. The influence of sibling behaviour and parental opinion operated differently within the two occupational groups. The psychological attributes of individuals attracted to a particular profession may also contribute to occupational patterns, specifically risk-taking and a concern for personal freedom.

Changes in the smoking behaviour, knowledge and opinion of medical students, 1972-1981.

To examine changes in medical students' smoking behaviour, knowledge and opinion over the last decade, a survey first conducted at the University of Manchester Medical School in 1972 was repeated in 1981. A postal questionnaire was sent to 1163 students, of whom 1112 (96%) replied. A substantial decline in cigarette smoking among medical students has occurred. This largely follows trends in the general population, medical education itself having made little contribution to the change. In 1972, 29% of students were cigarette smokers compared with 17% in 1981. The fall in cigarette smoking was more marked among men students rather than women, older rather than younger students, clinical rather than pre-clinical students. Cigarette consumption had also decreased as had the use of cigars and pipes among male students. The decline was already evident prior to students beginning their medical studies. A smaller expansion of smoking experience at medical school had occurred among the 1981 students, but, as in 1972, those who took up smoking or increased their consumption exceeded those who gave up or cut down. In 1981 the likelihood of taking up smoking or becoming a regular smoker at medical school was somewhat greater for women students than for men, although the numbers concerned were small. The survey reconfirmed the importance of the social environment in smoking behaviour. Modest changes had occurred in knowledge and opinion about smoking. Both the accuracy and scope of knowledge of students about the health hazards increased between 1972 and 1981, particularly among clinical students, who remained considerably better informed than their pre-clinical colleagues. As in 1972, knowledge had little impact on smoking behaviour. By 1981 nine out of ten students regarded smoking as a major risk to health, both clinical students and smokers being more likely to take this view than in 1972. Almost all students, irrespective of their smoking behaviour, found the evidence linking smoking to serious illness to some extent convincing, and by 1981 a somewhat greater proportion, 60%, found it very convincing, the tendency to do so increasing as they progressed through their course.

A pilot study of attendance for breast cancer screening.

Previous research has identified some characteristics related to attendance for breast cancer screening, but few research findings carry practical implications for the optimum organisation of the service. The present study describes the reactions of women attending one of the first breast screening units to be established in the U.K. following government directives. Responses to the invitation to be screened and reasons for attendance suggest ways in which the idea of screening can be conveyed in health education. Practical problems were few, but some negative features of the design of the screening unit and of the experience of being screened were identified. Recommendations for the organisation of breast cancer screening are presented using the typology of factors influencing health behaviour developed by Green et al.

The social definition of women's smoking behaviour.

The history of women's smoking behaviour is one of changing normative definitions. Recent trends have been explained in terms of the symbolic value of smoking, representing for women freedom and independence. This view is emphasised by advertising. However, other evidence suggests the continued existence of an older, more negative cultural stereotype. A two-part study of young women undergoing professional training for nursing and teaching throws some light on the way in which female smoking behaviour is currently socially interpreted. The first phase indicated that among the minority of parents who had expressed their attitudes towards their daughter's smoking in relation to sex-role norms, smoking was presented as unacceptable for women. More than half the sample perceived a negative cultural stereotype to be operating in contemporary society and two-thirds recognised its existence in the past. This stereotype presents smoking as a male behaviour and hence inappropriate for women. Women who do smoke are liable to be labelled as having unfeminine or degrading attributes. The stereotype operated more strongly in the general social background rather than in reference to personal relationships and hence its influence on contemporary behaviour is likely to be limited. It was rejected as out-dated or a male belief by some but nevertheless it represented the personal opinion of others. In terms of a more favourable definition the female smoker was perceived in terms of an elegant/sophisticated dimension and in relation to an extrovert personality. The view of sample members that the growing acceptability of women's smoking was related to social change indirectly supported the view that sees smoking as symbolic of independence. Those who saw smoking in neutral terms, i.e. as not having sex-role attributes, perceived smoking in this sense as normal social behaviour for men and women alike. The second phase suggested that smokers and non-smokers have divergent views about the image of the female smoker. The non-smoker's image was based on the older cultural stereotype ('unladylike'), whereas the smokers were more likely to take a view corresponding to the perspective that sees women's smoking as symbolic of social change and greater independence ('liberated'). The non-smokers had a clear and positive image of 'girls who don't smoke' ('feminine'), whereas for smokers the female non-smoker lacked a distinctive identity. The study thus suggests that traditional concepts of appropriate female behaviour continue to inhibit smoking among some women, whereas others perceive it as an aspect of independent behaviour.(ABSTRACT TRUNCATED AT 400 WORDS)

Reasons for non-attendance for computer-managed cervical screening: pilot interviews.

A pilot interview study looked at reasons why women did not attend a clinic following an invitation for a cervical smear test offered via a computer-managed scheme. Three broad issues were identified. First, the inaccuracy of the computer database (the FPC register) meant some women were inaccessible because they no longer lived at the address recorded. Other women were ineligible or unsuitable within the criteria of the scheme but had been sent invitations inappropriately because their screening records were incomplete or out of date. Second, aspects of service organisation and provision led to misclassification of some attenders as non-attenders and to various failures of communication such as non-receipt of the invitation or health education leaflet or unsuccessful attempts to rearrange appointments. In addition, the appointment or venue offered could be unsatisfactory. The third issue concerned the characteristics of the women which sometimes interacted with practical problems connected with service provision. Other women believed the test to be inappropriate for themselves while some were deterred by the prospect of the test itself. In general, embarrassment was pervasive and reflected in preferences for different types of service provision. Women who had neither attended nor been otherwise tested were particularly likely to express feelings of fear and fatalism. General attitudes to the test were favourable but this was not always applied personally. A typology of reasons for non-attendance for computer-managed cervical screening is presented.

Attendance for cervical screening--whose problem?

Despite the existence of an effective screening technique for cancer of the cervix, incidence and mortality from this disease have not declined in the United Kingdom. The basic problem is that women most at risk of the disease are under-represented in the screened population. The evidence for two different points of view to explain this situation is examined. These viewpoints are the failure of the women to attend, and the failure of the service to meet the needs of women. This paper argues that the evidence supports the view that the organisation of the existing screening service impedes the maximum participation of at-risk women. We discuss the features that an effective service needs to incorporate, and put forward principles for the development of a more effective screening system, namely, that it should be provider-initiated and user-oriented.

Headache and facial pain associated with head injury.

Head injury frequently results in headache and at times facial pain. Controversy concerns the relationship of injury in the head and neck area to chronic headache, particularly when no apparent structural traumatic lesion is demonstrable. Neuropathological studies suggest with concussion there is neuronal injury without gross pathology. Closed head injury of seemingly minor degrees may lead to chronic symptoms, often stereotypic, similar to those following concussion, and they have been described by the term post head trauma syndrome or postconcussional syndrome. Headache after head injury in an individual warrants careful medical, neurological, and neuroimaging assessment. The use of neuroimaging has greatly enhanced diagnosis in head-injured patients but has not satisfactorily clarified post head trauma symptoms in the less severely traumatized. Differential diagnosis is critical to avoid missing disabling, progressive, and life-threatening entities. In patients with head trauma neck injury should be sought. The headache may be nonspecific or mimic common nontraumatic headache disorders such as tension, migraine, and cluster. Recovery may include headache, psychological symptoms, and cognitive impairment. Neuropsychological assessment can be helpful in demonstrating deficiencies in mildly impaired individuals and explain the poor response to headache therapy in some patients suggesting more widespread injury. Therapy of head and facial pain follows the careful diagnosis and, if needed, assessment of the psychological status. Surgery, drug therapy, physical modalities, and at times a comprehensive neuropsychological rehabilitation program are necessary. Simple analgesics such as nonsteroidal antiinflammatory agents for short-term treatment and tricyclic antidepressants for chronic pain are most often effective in patients without structural damage. More complex medication regimens may include beta adrenergic blockers and monamine oxidase inhibitors. Since many injuries result from motor vehicle accidents, work-related factors, and other instances in which litigation may result, legal elements may be involved. Most often the prognosis is favorable for resolution of symptoms but a small percentage of patients will have persistent symptoms after three years. The notion that litigation prolongs the duration of the illness is not valid. In the past two decades great advances have been made in neurodiagnosis, and parallel therapeutic advances are expected in the near future.

Investigation of fatigue failure of S-65-HL "Super Tygon" roller pump tubing.

A failure analysis was performed on Norton S-65-HL Tygon tubing. Fatigue testing was performed on four sizes of this tubing, and essentially showed how the tubing wears out. A dynamic "life hours to failure" test, which was performed on the 3/8" internal diameter (ID) size, quantified when the tubing ruptured. Based on results of laboratory testing and the institution's clinical extracorporeal membrane oxygenation (ECMO) experience, a reasonable life expectancy for the 3/8" S-65-HL Tygon size was determined for use in this institution's neonatal ECMO system. An understanding of the expected performance of roller pump tubing-an integral component of the ECMO system-is imperative to providing safe, effective extracorporeal life support.

Outreach teaching: is this the future for dental education?

Increasingly clinical teaching for all health professionals is moving out of teaching hospitals and into community settings. A recent workshop reviewed the place of outreach teaching in undergraduate dental education. This paper defines outreach teaching in terms of its main components; identifies its benefits for different stakeholders; sets out what is required to make it work; and looks at current trends offering opportunities for expansion.

Muscle contraction headache. Overview and update of a common affliction.

Muscle contraction headache usually can be correctly diagnosed on the basis of a thorough patient history and physical examination, although diagnostic tests may be necessary to exclude structural or inflammatory disease. Often, symptoms are directly related to emotional conflicts. In most cases, the primary care physician can provide treatment, which includes understanding and emotional support. Pharmacologic therapy and biofeedback are effective in controlling symptoms. Depression should be suspected in patients with chronic headache. Referral for neurologic or psychiatric consultation should be considered if the diagnosis is unclear or therapy is unsatisfactory.