Michael B. Bracken

A randomized, controlled trial of methylprednisolone or naloxone in the treatment of acute spinal-cord injury: Results of the second national acute spinal cord injury study

In 1990, the Second National Acute Spinal Cord Injury Study reported that high-dosage methylprednisolone improves neurologic recovery in spinal-injured humans. The study showed that patients who received the drug within 8 hr after injury improved, whereas those who received the drug later did not. The drug significantly increased recovery even in severely injured patients who were admitted with no motor or sensory function below the lesion, contradicting a long-held dogma that such patients would not recover. Some researchers, however, have questioned the stratification of the patient population, the use of summed neurologic change scores, and the absence of functional assessments. The stratification by injury severity and treatment time was planned a priori and based on objective criteria. Detailed analyses revealed no differences between groups attributable to stratification or randomization. While multivariate analyses of the summed neurologic scores were used, the conclusions were corroborated by other analytical approaches that did not rely on summed scores. For example, treatment with methylprednisolone more than doubled the probability that patients would convert from quadriplegia or paraplegia to quadriparesis or paraparesis, analgesia to hypalgesia, and anesthesia to hypesthesia. The treatment also significantly improved neurologic scores in lumbosacral segments, indicating that beneficial effects were not limited to segments close to the lesion site. The treatment did not significantly affect mortality or morbidity. The study strongly suggests that methylprednisolone has significant beneficial effects in human spinal cord injury, that these effects occur only when the drug is given within 8 hr, and that it helps even in patients with severe spinal cord injuries. These conclusions have important implications for spinal cord injury care and research.

International standards for neurological and functional classification of spinal cord injury

International Standards for Neurological and Functional Classification of Spinal Cord Injury

A Randomized, Controlled Trial of Methylprednisolone or Naloxone in the Treatment of Acute Spinal-Cord Injury

Abstract Studies in animals indicate that methylprednisolone and naloxone are both potentially beneficial in acute spinal-cord injury, but whether any treatment is clinically effective remains uncertain. We evaluated the efficacy and safety of methylprednisolone and naloxone in a multicenter randomized, double-blind, placebo-controlled trial in patients with acute spinal-cord injury, 95 percent of whom were treated within 14 hours of injury. Methylprednisolone was given to 162 patients as a bolus of 30 mg per kilogram of body weight, followed by infusion at 5.4 mg per kilogram per hour for 23 hours. Naloxone was given to 154 patients as a bolus of 5.4 mg per kilogram, followed by infusion at 4.0 mg per kilogram per hour for 23 hours. Placebos were given to 171 patients by bolus and infusion. Motor and sensory functions were assessed by systematic neurologic examination on admission and six weeks and six months after injury. After six months the patients who were treated with methylprednisolone within eigh...

Administration of methylprednisolone for 24 or 48 hours or tirilazad mesylate for 48 hours in the treatment of acute spinal cord injury. Results of the Third National Acute Spinal Cord Injury Randomized Controlled Trial. National Acute Spinal Cord Injury Study.

OBJECTIVE To compare the efficacy of methylprednisolone administered for 24 hours with methyprednisolone administered for 48 hours or tirilazad mesylate administered for 48 hours in patients with acute spinal cord injury. DESIGN Double-blind, randomized clinical trial. SETTING Sixteen acute spinal cord injury centers in North America. PATIENTS A total of 499 patients with acute spinal cord injury diagnosed in National Acute Spinal Cord Injury Study (NASCIS) centers within 8 hours of injury. INTERVENTION All patients received an intravenous bolus of methylprednisolone (30 mg/kg) before randomization. Patients in the 24-hour regimen group (n=166) received a methylprednisolone infusion of 5.4 mg/kg per hour for 24 hours, those in the 48-hour regimen group (n=167) received a methylprednisolone infusion of 5.4 mg/kg per hour for 48 hours, and those in the tirilazad group (n=166) received a 2.5 mg/kg bolus infusion of tirilazad mesylate every 6 hours for 48 hours. MAIN OUTCOME MEASURES Motor function change between initial presentation and at 6 weeks and 6 months after injury, and change in Functional Independence Measure (FIM) assessed at 6 weeks and 6 months. RESULTS Compared with patients treated with methylprednisolone for 24 hours, those treated with methylprednisolone for 48 hours showed improved motor recovery at 6 weeks (P=.09) and 6 months (P=.07) after injury. The effect of the 48-hour methylprednisolone regimen was significant at 6 weeks (P=.04) and 6 months (P=.01) among patients whose therapy was initiated 3 to 8 hours after injury. Patients who received the 48-hour regimen and who started treatment at 3 to 8 hours were more likely to improve 1 full neurologic grade (P=.03) at 6 months, to show more improvement in 6-month FIM (P=.08), and to have more severe sepsis and severe pneumonia than patients in the 24-hour methylprednisolone group and the tirilazad group, but other complications and mortality (P=.97) were similar. Patients treated with tirilazad for 48 hours showed motor recovery rates equivalent to patients who received methylprednisolone for 24 hours. CONCLUSIONS Patients with acute spinal cord injury who receive methylprednisolone within 3 hours of injury should be maintained on the treatment regimen for 24 hours. When methylprednisolone is initiated 3 to 8 hours after injury, patients should be maintained on steroid therapy for 48 hours.

How to increase value and reduce waste when research priorities are set

The increase in annual global investment in biomedical research--reaching US

Asthma prevalence among pregnant and childbearing-aged women in the United States: estimates from national health surveys.

240 billion in 2010--has resulted in important health dividends for patients and the public. However, much research does not lead to worthwhile achievements, partly because some studies are done to improve understanding of basic mechanisms that might not have relevance for human health. Additionally, good research ideas often do not yield the anticipated results. As long as the way in which these ideas are prioritised for research is transparent and warranted, these disappointments should not be deemed wasteful; they are simply an inevitable feature of the way science works. However, some sources of waste cannot be justified. In this report, we discuss how avoidable waste can be considered when research priorities are set. We have four recommendations. First, ways to improve the yield from basic research should be investigated. Second, the transparency of processes by which funders prioritise important uncertainties should be increased, making clear how they take account of the needs of potential users of research. Third, investment in additional research should always be preceded by systematic assessment of existing evidence. Fourth, sources of information about research that is in progress should be strengthened and developed and used by researchers. Research funders have primary responsibility for reductions in waste resulting from decisions about what research to do.

Birthweight and mortality in adulthood: a systematic review and meta-analysis

PURPOSE Asthma is a major complication of pregnancy, but there are currently no reliable national estimates for the United States of asthma prevalence in pregnancy or in the childbearing years. METHODS The prevalence of asthma among pregnant women and all childbearing-aged women was estimated and examined by age group using the National Health Interview Survey (NHIS), 1997-2000, the Behavioral Risk Factor Surveillance System (BRFSS), 2000-2001, and the Third National Health and Nutrition Examination Survey (NHANES III), 1988-1994. Time trends were explored using NHANES II (1976-1980) and NHANES III (1988-1994). RESULTS Asthma was estimated to affect from 88,573 to 190,650 pregnant women between 1997 and 2001, or approximately 3.7% to 8.4% of pregnant women in the United States. A slightly lower estimate of 3.2% was obtained for the period between 1988 and 1994. Among adult women of childbearing age, a two-fold increase in asthma from 2.9% to 5.8% occurred between 1976-1980 and 1988-1994. Among women aged 18 to 24, the increase was three-fold, from 1.8% to 6.0%. CONCLUSION The prevalence of asthma during pregnancy may be higher than previously estimated and appears to be continuing to increase.

Asthma symptoms, severity, and drug therapy: a prospective study of effects on 2205 pregnancies.

BACKGROUND Small birth size may be associated with increased risk of cardiovascular diseases (CVD), whereas large birth size may predict increased risk of obesity and some cancers. The net effect of birth size on long-term mortality has only been assessed in individual studies, with conflicting results. METHODS The Meta-analyses of Observational Studies in Epidemiology (MOOSE) guidelines for conducting and reporting meta-analysis of observational studies were followed. We retrieved 22 studies that assessed the association between birthweight and adult mortality from all causes, CVD or cancer. The studies were systematically reviewed and those reporting hazard ratios (HRs) and 95% confidence intervals (95% CIs) per kilogram (kg) increase in birthweight were included in generic inverse variance meta-analyses. RESULTS For all-cause mortality, 36,834 deaths were included and the results showed a 6% lower risk (adjusted HR = 0.94, 95% CI: 0.92-0.97) per kg higher birthweight for men and women combined. For cardiovascular mortality, the corresponding inverse association was stronger (HR = 0.88, 95% CI: 0.85-0.91). For cancer mortality, HR per kg higher birthweight was 1.13 (95% CI: 1.07-1.19) for men and 1.04 (95% CI: 0.98-1.10) for women (P(interaction) = 0.03). Residual confounding could not be eliminated, but is unlikely to account for the main findings. CONCLUSION These results show an inverse but moderate association of birthweight with adult mortality from all-causes and a stronger inverse association with cardiovascular mortality. For men, higher birthweight was strongly associated with increased risk of cancer deaths. The findings suggest that birthweight can be a useful indicator of processes that influence long-term health.

Clinically useful measures of effect in binary analyses of randomized trials

OBJECTIVE To prospectively examine in pregnant women whether asthma or asthma therapy influenced preterm delivery, intrauterine grown restriction (IUGR), or birthweight. METHODS We enrolled 873 pregnant women with a history of asthma, of whom 778 experienced asthma symptoms or took medication, and 1333 women with no asthma history, including 884 women with neither asthma diagnosis nor symptoms and 449 with symptoms but no diagnosis. Asthma symptoms, medication, and severity were classified according to 2002 Global Initiative for Asthma guidelines. RESULTS Preterm delivery was not associated with asthma diagnosis, severity, or symptoms but was associated with use of controller medications, independent of symptoms, specifically oral steroids and theophylline. Gestation was reduced by 2.22 weeks in women using oral steroids daily (P =.001) and 1.11 weeks after theophylline (P =.002). We observed a 24% (5-47%) increased risk for IUGR with each increased symptom step, which increased further in symptomatic women with no asthma diagnosis (31%, 4-65%) compared with women with neither asthma nor symptoms. CONCLUSIONS We found no effect of asthma symptoms or severity on preterm delivery but observed increased risks associated with use of oral steroid and theophylline. Intrauterine growth restriction was associated with asthma severity, which possibly reflects a hypoxic fetal effect. Women with asthma symptoms but no diagnosis were at particular risk of undermedication and delivering IUGR infants. These observations support guidelines that advocate active management of pregnant patients with mild or moderate asthma with beta(2) agonists, with oral steroids added only if severity increases. Symptomatic patients without an asthma diagnosis might need to be equally managed.

The relation between fungal propagules in indoor air and home characteristics

The results of a randomized clinical trial can be reported using relative and/or absolute estimators of treatment effect. These various measures convey different information, and the choice can influence the physicians appreciation of the size of treatment effect and, subsequently, treatment decisions. We compare the estimators with respect to the clinically relevant information conveyed to physicians, and identify which clinical questions can and cannot be answered directly by each. We also identify opportunities for misinterpretation when one estimator is substituted for another, or when an estimator is mislabeled. Clinically important questions are addressed most directly by reporting both relative and absolute effects using relative risk and its complement, relative risk reduction, and risk difference and its reciprocal, number needed to treat. This is true of estimates of treatment effect derived from a single trial and also from meta-analysis of a group of trials. Because the control groups risk affects the numerical value of the odds ratio, the odds ratio cannot substitute for the risk ratio in conveying clinically important information to physicians. This is especially important when large treatment effects are shown in trials carried out in populations at high baseline risk.