Neurology
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Clinical trials of opioid analgesics for chronic pain are recognized to frequently fail to distinguish the analgesic effect from placebo, despite known efficacy of the drug. This paper reviews the methodologic features of such trials that may be associated with risk of failure. A literature search yielded 23 randomized placebo-controlled studies of opioids with at least one week of continuous treatment; contacting pharmaceutical companies yielded six additional studies. ⋯ Study designs that lead to high dropout rates lack internal validity, unless dropout is the intended endpoint of the trial. Opioid analgesics should be studied in a manner that is clinically relevant, and that supports internal validity. More systematic attention is needed to clinical research methodology.
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Pharmacologic treatment of pain has made tremendous advances in recent years, and multiple clinical trials support the usefulness of psychological interventions in reducing pain, disability, and even costs, in a number of chronically painful conditions. Despite the widespread use of combined pharmacologic and psychological treatments in clinical care, little is known about the potential for these two very different types of interventions to provide additive or possibly synergistic effects. After briefly reviewing of the clinical trial literature comparing and combining psychological and pharmacologic interventions for chronically painful conditions, this article discusses two key challenges to future trials. ⋯ The second challenge pertains to issues of trial design when pharmacologic and psychological treatments for pain are compared and combined. Trials comparing active treatments that are as diverse as psychological and pharmacologic treatments require specific features, such as large sample sizes, active placebo controls, both immediate and delayed outcome assessments, and broad measures of outcome that include health-care utilization and cost. Some lessons learned from the psychiatric literature comparing and combining psychological and pharmacologic treatments are integrated into recommendations for future trials evaluating existing and new treatments for chronically painful conditions.
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Primary progressive multiple sclerosis (PPMS) has a distinct clinical phenotype and has historically been understudied with few longitudinal natural history studies spanning a reasonable time period. The authors examined patient characteristics, disease progression, and associated risk factors in the PP population of British Columbia, Canada. ⋯ Progression of disability was slower than found in previous primary progressive multiple sclerosis natural history studies. However, considerable variation existed, with few predictors, other than "sooner to cane, sooner to wheelchair."
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In patients with stroke, gradient-echo MRI commonly detects microbleeds, indicating small artery disease with increased risk of macroscopic intracranial bleeding. Antithrombotic treatments are frequently prescribed after TIA and stroke, but there have been no previous studies of microbleeds in TIA. Because microbleeds may predict the hemorrhagic risk of antithrombotic treatments, we studied the prevalence of microbleeds, risk factors, and pathophysiologic mechanisms in patients with ischemic stroke and TIA. ⋯ Microbleeds are common in ischemic stroke but rare in TIA, an observation not explained by differences in vascular risk factors or severity of white matter disease seen on T2 MRI. This finding has implications for the safety of antithrombotic therapy and clinical trial design in the two groups. Microbleeds may also be a new marker for severe microvascular pathology with increased risk of permanent cerebral infarction.