| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Phase II futility trial designs considered by Tilley et al. may decrease time to identify agents unworthy of further study and reduce subject exposure to ineffective futile treatments. Futility trials depend on clinically relevant or historically derived references to assess futility. Failure to find futility does not imply efficacy.
see page 628
Efficient phase II clinical trial design for ALS
Levy et al. describe the design of the Clinical Trial of High Dose Coenzyme Q10 in ALS (QALS study). A selection procedure to identify a preferred dose and a futility analysis reduce sample size and trial duration.
see page 660
Creatine and minocycline in early PD
The National Institute of Neurologic Disorders and Stroke (NET-PD) investigators conducted a futility trial of creatine and minocycline in early PD. The goal was to test whether these drugs altered the course of early PD relative to a threshold for progression derived from historical data. Both creatine and minocycline slowed disease progression relative to the futility threshold, suggesting that they merit further clinical study.
see page 664
The editorial by Schwid and Cutter about these three articles notes that Phase III studies require hundreds of patients to be followed for at least 2 years and cost millions of dollars. Preliminary evidence that a treatment is safe and likely to be helpful is essential before making such a large investment of human resources. Futility studies identify agents unlikely to demonstrate benefit rather than identifying the most promising agents. The big advantage of the futility design is that it allows some agents to be weeded out at the preliminary study stage while requiring a fraction of the patients and resources of more conventional efficacy studies. However, non-futile agents are less likely to show benefit in Phase III trials than agents demonstrating preliminary evidence of efficacy, unless futility thresholds are set stringently. After decades with little to offer patients with neurodegenerative diseases, being forced to choose between non-futile treatments to pursue in additional studies is a good problem to have.
see page 626
Neuropsychological deficits in long-term cannabis users
Messinis et al. studied neuropsychological functioning in long-term, heavy cannabis users (15.9 years) and found deficits on verbal fluency, memory, attention, and psychomotor speed compared to shorter term users (6.95 years).
see page 737
Recurrent stroke and cardiac risks after stroke
Dhamoon et al. followed 655 patients after their first ischemic stroke for up to 5 years. The risk of fatal cardiac events was almost twice that of fatal stroke, although risk of all recurrent strokes was approximately twice overall cardiac risk.
see page 641
Early interferon ß-1a treatment more effective
In the CHAMPIONS study, treatment with interferon ß-1a IM once weekly immediately following a first clinical demyelinating event delayed the rate of development of MS by 35% after 5 years compared to delayed initiation of therapy.
see page 678
Thrombolysis in pregnant women
Murugappan et al. treated eight pregnant women with stroke with thrombolytics. Seven recovered, but three were therapeutically aborted, while two miscarried. Two delivered healthy babies. Pregnant women may be given thrombolytics safely but risks/benefits to mother/fetus must be carefully weighed.
see page 768
The natural history of primary lateral sclerosis
Gordon et al. studied 39 patients diagnosed with PLS. Those with no lower motor neuron (LMN) signs 4 years after onset progressed slowly and maintained function. If LMN signs appeared within 4 years, disability was greater. The diagnosis of PLS is more secure after 4 years.
see page 647
The editorial by Rosenfeld and Swash notes that Gordon et al. have initiated a critical process of categorizing subgroups of patients with ALS by addressing a relatively easily identified population of patients with PLS. They suggest that this is one of many steps to categorize other ALS subgroups: indolent forms of motor neuron disease, rapidly aggressive forms, focal or monomelic forms, lower motor neuron-predominant presentations, ALS-FTD, generalized motor neuron degeneration, and asymmetric or multifocal forms of motor neuron degeneration. The search for environmental triggers and for treatment demands such a strategy.
see page 624
Patent foramen ovale, migraine, and stroke
Anzola et al. quantitated the right to left shunt from a patent foramen ovale in 420 consecutive patients with migraine, cryptogenic stroke, or neither condition and found that the patients with migraine and stroke had the largest shunt vs either migraine or stroke alone.
see page 765
Haptoglobin as a risk factor for cerebral artery vasospasm
Borsody et al. evaluated the relationship between the type of haptoglobin expressed by patients with subarachnoid hemorrhage and the development of cerebral artery vasospasm. Patients who expressed haptoglobins containing the 
2 subunit appeared to have a higher rate of vasospasm than did other patients.
see page 634
Cerebrovascular reactivity and subarachnoid hemorrhage
Frontera et al. found that in patients with acute subarachnoid hemorrhage, impending symptomatic vasospasm correlated with the appearance of abnormal cerebral vasoreactivity using transcranial Doppler and CO2 inhalation.
see page 727
The editorial by Alejandro A. Rabinstein about these two articles notes that differentiation of vasospasm from other complications of SAH—hydrocephalus, cerebral edema, aneurysmal rebleeding, and hyponatremia—may be difficult. The amount of blood in the SA space on initial CT, young age, and history of smoking are risk factors, but their predictive value is limited. Both Neurology studies tested novel, simple tools for prediction and diagnosis of vasospasm. The Borsody et al. study needs to be confirmed in a larger cohort that incorporates clinical outcome measures (such as symptomatic vasospasm) and assessment of cognitive and functional status but suggests that haptoglobin typing may be clinically useful. The finding that abnormal CO2 reactivity was significantly associated with the occurrence of symptomatic vasospasm could reflect abnormal vasomotor reactivity that is a nonspecific risk factor for neurologic decline. However, disturbed microcirculatory function identifiable by abnormal responses to CO2 exposure could be responsible for this subcortical ischemia and represent a target for future therapeutic strategies.
see page 622
Memory impairment in now abstinent MDMA users and continued users
Zakzanis and Campbell investigated the functional consequences of continued neurotoxicity of (±)3, 4-methylenedioxymethamphetamine (MDMA) use in longitudinal follow-up. Current users demonstrated further decline in memory ability while former users improved or remained static on memory measures.
see page 740
|
|
|
Related articles in Neurology:
| ||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
