Predicting the geoeffective properties of coronal mass ejections: current status, open issues and path forward.

Much progress has been made in the study of coronal mass ejections (CMEs), the main drivers of terrestrial space weather thanks to the deployment of several missions in the last decade. The flow of energy required to power solar eruptions is beginning to be understood. The initiation of CMEs is routinely observed with cadences of tens of seconds with arc-second resolution. Their inner heliospheric evolution can now be imaged and followed routinely. Yet relatively little progress has been made in predicting the geoeffectiveness of a particular CME. Why is that? What are the issues holding back progress in medium-term forecasting of space weather? To answer these questions, we review, here, the measurements, status and open issues on the main CME geoeffective parameters; namely, their entrained magnetic field strength and configuration, their Earth arrival time and speed, and their mass (momentum). We offer strategies for improving the accuracy of the measurements and their forecasting in the near and mid-term future. To spark further discussion, we incorporate our suggestions into a top-level draft action plan that includes suggestions for sensor deployment, technology development and modelling/theory improvements. This article is part of the theme issue 'Solar eruptions and their space weather impact'.

Assessing the Quality of Models of the Ambient Solar Wind.

In this paper we present an assessment of the status of models of the global Solar Wind in the inner heliosphere. We limit our discussion to the class of models designed to provide solar wind forecasts, excluding those designed for the purpose of testing physical processes in idealized configurations. In addition, we limit our discussion to modeling of the 'ambient' wind in the absence of coronal mass ejections. In this assessment we cover use of the models both in forecast mode and as tools for scientific research. We present a brief history of the development of these models, discussing the range of physical approximations in use. We discuss the limitations of the data inputs available to these models and its impact on their quality. We also discuss current model development trends.

Ensemble downscaling in coupled solar wind-magnetosphere modeling for space weather forecasting.

Advanced forecasting of space weather requires simulation of the whole Sun-to-Earth system, which necessitates driving magnetospheric models with the outputs from solar wind models. This presents a fundamental difficulty, as the magnetosphere is sensitive to both large-scale solar wind structures, which can be captured by solar wind models, and small-scale solar wind "noise," which is far below typical solar wind model resolution and results primarily from stochastic processes. Following similar approaches in terrestrial climate modeling, we propose statistical "downscaling" of solar wind model results prior to their use as input to a magnetospheric model. As magnetospheric response can be highly nonlinear, this is preferable to downscaling the results of magnetospheric modeling. To demonstrate the benefit of this approach, we first approximate solar wind model output by smoothing solar wind observations with an 8 h filter, then add small-scale structure back in through the addition of random noise with the observed spectral characteristics. Here we use a very simple parameterization of noise based upon the observed probability distribution functions of solar wind parameters, but more sophisticated methods will be developed in the future. An ensemble of results from the simple downscaling scheme are tested using a model-independent method and shown to add value to the magnetospheric forecast, both improving the best estimate and quantifying the uncertainty. We suggest a number of features desirable in an operational solar wind downscaling scheme. KEY POINTS: Solar wind models must be downscaled in order to drive magnetospheric models Ensemble downscaling is more effective than deterministic downscaling The magnetosphere responds nonlinearly to small-scale solar wind fluctuations.

Killed Mycobacterium vaccae suspension in children with moderate-to-severe atopic dermatitis: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: The hygiene hypothesis is often proposed to explain the high prevalence of atopy in the western world. Dysregulation of the immune system may result from inadequate exposure to micro-organisms such as mycobacteria. A small trial suggested that a killed extract of Mycobacterium vaccae ameliorates atopic dermatitis (AD). OBJECTIVES: To confirm in a large clinical trial whether killed M. vaccae ameliorates AD in 5-16-year-old children. METHODS: This was a randomized, placebo-controlled, double-blind, multi-centre study of the effect of intradermal injection of killed M. vaccae (0.1 or 1 mg) on patients, aged 5-16, with moderate-to-severe AD. Patients were followed up for 24 weeks. The primary end point was the change in severity of AD at 12 weeks, assessed using the six area, six-sign, atopic dermatitis (SASSAD) score. Secondary end points included changes in disease extent, patient's global assessment and children's dermatology life quality index. RESULTS: There were 166 patients randomized. The mean SASSAD score fell to a similar degree at week 12 in all treatment arms: from 33 to 24, (26%) in the high-dose group, from 30 to 23 (25%) in the low-dose group and from 36 to 27 (24%) in the placebo group (P>0.05). Secondary end points followed the same trend. Adverse events were generally those expected to occur in this population. Injection site reactions occurred in 32 patients at week 4. CONCLUSIONS: M. vaccae was no more effective than the placebo in ameliorating the severity of AD.

Efficacy and tolerability of sumatriptan tablets administered during the mild-pain phase of menstrually associated migraine.

Two randomised, double-blind, parallel-group, placebo-controlled clinical trials were conducted to assess the efficacy of sumatriptan tablets, 50mg and 100mg, for treatment during the mild-pain phase of a menstrually associated migraine among patients who typically experienced moderate to severe migraine preceded by an identifiable phase of mild pain. Subjects (n = 403 in Study 1 and n = 349 in Study 2) treated one menstrually associated migraine on an outpatient basis. The results demonstrate that sumatriptan tablets, 50 mg or 100 mg, were significantly more effective than placebo at conferring pain-free response 1 h and 2 h post-dose; migraine-free response (i.e. no pain and no associated symptoms) 2 h post-dose; returning patients to normal functioning 2 h post-dose; and conferring sustained freedom from pain from 2 through 24 h post-dose. Although the studies were not designed or statistically powered to show differences between the sumatriptan doses, a trend for slightly higher efficacy was observed for the 100-mg dose compared with the 50-mg dose on many measures. Both doses of sumatriptan were well-tolerated. The only adverse events reported in more than 2% of subjects in a treatment group were nausea, paresthesia, dizziness and malaise/fatigue, all of which were reported at incidences comparable to or slightly higher than those with placebo. Considered in the context of other findings, these data suggest that--with menstrually associated migraine as with non-menstrual migraine--optimal therapeutic benefit of sumatriptan tablets may be realised when they are administered during the mild-pain phase of an attack rather than delaying treatment until headache is moderate or severe.

Switching patients with migraine from sumatriptan to other triptans increases primary care costs.

Treatment of migraine with triptans is highly effective, although cost considerations may prompt a change in therapy. This retrospective database analysis of 3196 patients with migraine, established on sumatriptan therapy, found that 54% of the 292 experiencing a triptan switch returned to sumatriptan within 15 months, suggesting that the alternative was less acceptable. Excluding patients with unusually high use of triptans (> or = 208 tablets/year), switching therapy resulted in a significant increase of pounds sterling 53/patient in total costs, compared with patients continuing on sumatriptan (p = 0.014). Cost savings (pounds sterling 17/patient over 15 months) were observed only among the 41% of patients in whom the initial switch was successful and did not result in a further switch or return to sumatriptan. Among patients who were relatively low cost initially, switching resulted in increased costs, irrespective of the outcome. This study suggests that there is no economic justification for switching from sumatriptan to another triptan.

Efficacy, tolerability, and patient satisfaction with 50- and 100-mg sumatriptan tablets in those initially dissatisfied with the efficacy of 50-mg sumatriptan tablets.

BACKGROUND: Both 50- and 100-mg sumatriptan tablets are effective and well tolerated in the acute treatment of migraine. However, given a choice between the 2 doses, many patients in clinical practice and clinical studies prefer the 100-mg dose. OBJECTIVE: This study was designed to assess whether patients initially dissatisfied with the efficacy of 50-mg sumatriptan tablets would be satisfied with 100-mg sumatriptan tablets. METHODS: In phase 1 of the study, triptan-naive patients with migraine (International Headache Society diagnosis) received open-label treatment of 3 migraine attacks with 50-mg sumatriptan tablets. At the end of phase 1, those who were dissatisfied with the efficacy but satisfied with the tolerability of 50-mg sumatriptan tablets entered phase 2 and were randomized in a double-blind, parallel-group fashion to receive either 50- or 100-mg sumatriptan tablets for the treatment of 3 attacks. Patients who were satisfied with the efficacy or dissatisfied with the tolerability of the 50-mg tablets in phase 1 were given the option of continuing open-label treatment with 50-mg sumatriptan tablets in phase 2. The primary end point was the percentage of patients satisfied with medication at the end of phase 2 double-blind treatment. Patient satisfaction with specific medication attributes was assessed using the Patient Perception of Migraine Questionnaire. RESULTS: Seven hundred twenty-two patients were enrolled in phase 1 of the study (the intent-to-treat population), 609 of whom had evaluable satisfaction data at the end of open-label treatment. Three hundred twenty-six (54%) of these patients were satisfied with 50-mg sumatriptan tablets, whereas 283 (46%) were not satisfied. Among those who were dissatisfied, lack of efficacy was cited as the sole reason for dissatisfaction by 242 (86%). Two hundred thirty-one of those who were dissatisfied with efficacy only and wished to continue the study were randomized to double-blind treatment with either 50-mg sumatriptan tablets (n = 123; 82% female, 18% male; mean age, 37.6 years) or 100-mg sumatriptan tablets (n = 108; 86% female, 14% male; mean age, 36.0 years). The remaining 310 patients elected to continue open-label treatment with 50-mg sumatriptan tablets. At the end of double-blind treatment, 64 of 101 patients (63%) in the 100-mg group indicated that they were satisfied with treatment, compared with 55 of 113 (49%) in the 50-mg group (P = 0.031). Across the 3 attacks treated in the double-blind phase. headache relief 2 hours postdose was reported by 47% to 53% of patients in the 50-mg group and 45% to 60% of patients in the 100-mg group. The overall incidence of patients reporting > or =1 adverse event was 19% (23/123) in the 50-mg group and 22% (24/108) in the 100-mg group. CONCLUSIONS: For most patients, 50 mg is the appropriate starting dose of sumatriptan tablets. In patients who experience inadequate relief with 50 mg, increasing the dose to 100 mg is an appropriate therapeutic option.

A double-blind placebo-controlled study assessing the efficacy and tolerability of 50 mg sumatriptan tablets in the acute treatment of migraine. Sumatriptan Tablets S2CM07 Study Group.

BACKGROUND: Oral sumatriptan 50 mg has been found to have good efficacy and tolerability in the acute treatment of migraine but has been less well studied than the 100 mg dose. METHODS: This was a double-blind, parallel-group study (Glaxo Wellcome protocol number S2CM07) comparing the efficacy and safety of sumatriptan 50 mg tablets with placebo in the acute treatment of migraine. Patients treated three migraine attacks with study medication; a second, optional dose was available for treating recurrent headache. Of the 560 patients randomized, 485 treated at least one attack, 411 at least two attacks, and 362 three attacks. The primary efficacy measure was the proportion of patients who had obtained complete or almost complete headache relief at 4 h after dosing. RESULTS: For all attacks, a significantly greater proportion of patients experienced headache relief at 4 h with sumatriptan 50 mg tablets than with placebo (59% to 62% versus 32% to 42%; P = 0.005). The same was true at 3 h across all attacks, and at 2 h for attacks 1 and 2 (49% versus 23% and 45% versus 29%, respectively). Although sumatriptan and placebo were associated with similar incidences of recurrence, sumatriptan was associated with a longer time to recurrence. The incidence of adverse events with sumatriptan was similar to that with placebo, and there was no increase in adverse events associated with use of a second dose to treat recurrence. CONCLUSIONS: Sumatriptan 50 mg tablets are well tolerated and efficacious in relieving migraine headache.