Blinded vs. unblinded peer review of manuscripts submitted to a dermatology journal: a randomized multi-rater study.

BACKGROUND: Submissions to medical and scientific journals are vetted by peer review, but peer review itself has been poorly studied until recently. One concern has been that manuscript reviews in which the reviewer is unblinded (e.g. knows author identity) may be biased, with an increased likelihood that the evaluation will not be strictly on scientific merits. OBJECTIVES: The purpose of this study was to compare the outcomes of blinded and unblinded reviews of manuscripts submitted to a single dermatology journal via a randomized multi-rater study. MATERIALS AND METHODS: Forty manuscripts submitted to the journal Dermatologic Surgery were assessed by four reviewers, two of whom were randomly selected to be blinded and two unblinded regarding the identities of the manuscripts' authors. The primary outcome measure was the initial score assigned to each manuscript by each reviewer characterized on an ordinal scale of 1-3, with 1 = accept; 2 = revise (i.e. minor or major revisions) and 3 = reject. Subgroup analysis compared the primary outcome measure across manuscripts from U.S. corresponding authors and foreign corresponding authors. The secondary outcome measure was word count of the narrative portion (i.e. comments to editor and comments to authors) of the reviewer forms. RESULTS: There was no significant difference between the scores given to manuscripts by unblinded reviewers and blinded reviewers, both for manuscripts from the U.S. and for foreign submissions. There was also no difference in word count between unblinded and blinded reviews. CONCLUSIONS: It seems, at least in the case of one dermatology journal, that blinding during peer review does not appear to affect the disposition of the manuscript. To the extent that review word count is a proxy for review quality, there appears to be no quality difference associated with blinding.

Extent of spontaneous motor recovery after traumatic cervical sensorimotor complete spinal cord injury.

STUDY DESIGN: Retrospective, longitudinal analysis of motor recovery data from individuals with cervical (C4-C7) sensorimotor complete spinal cord injury (SCI) according to the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI). OBJECTIVES: To analyze the extent and patterns of spontaneous motor recovery over the first year after traumatic cervical sensorimotor complete SCI. METHODS: Datasets from the European multicenter study about SCI (EMSCI) and the Sygen randomized clinical trial were examined for conversion of American Spinal Injury Association (ASIA) Impairment Scale (AIS) grade, change in upper extremity motor score (UEMS) or motor level, as well as relationships between these measures. RESULTS: There were no overall differences between the EMSCI and Sygen datasets in motor recovery patterns. After 1 year, up to 70% of subjects spontaneously recovered at least one motor level, but only 30% recovered two or more motor levels, with lesser values at intermediate time points. AIS grade conversion did not significantly influence motor level changes. At 1 year, the average spontaneous improvement in bilateral UEMS was 10-11 motor points. There was only moderate relationship between a change in UEMS and a change in cervical motor level (r(2)=0.30, P<0.05). Regardless of initial cervical motor level, most individuals recover a similar number of motor points or motor levels. CONCLUSION: Careful tracking of cervical motor recovery outcomes may provide the necessary sensitivity and accuracy to reliably detect a subtle, but meaningful treatment effect after sensorimotor complete cervical SCI. The distribution of the UEMS change may be more important functionally than the total UEMS recovered.

Guidelines for the conduct of clinical trials for spinal cord injury (SCI) as developed by the ICCP panel: clinical trial outcome measures.

An international panel reviewed the methodology for clinical trials of spinal cord injury (SCI), and provided recommendations for the valid conduct of future trials. This is the second of four papers. It examines clinical trial end points that have been used previously, reviews alternative outcome tools and identifies unmet needs for demonstrating the efficacy of an experimental intervention after SCI. The panel focused on outcome measures that are relevant to clinical trials of experimental cell-based and pharmaceutical drug treatments. Outcome measures are of three main classes: (1) those that provide an anatomical or neurological assessment for the connectivity of the spinal cord, (2) those that categorize a subject's functional ability to engage in activities of daily living, and (3) those that measure an individual's quality of life (QoL). The American Spinal Injury Association impairment scale forms the standard basis for measuring neurologic outcomes. Various electrophysiological measures and imaging tools are in development, which may provide more precise information on functional changes following treatment and/or the therapeutic action of experimental agents. When compared to appropriate controls, an improved functional outcome, in response to an experimental treatment, is the necessary goal of a clinical trial program. Several new functional outcome tools are being developed for measuring an individual's ability to engage in activities of daily living. Such clinical end points will need to be incorporated into Phase 2 and Phase 3 trials. QoL measures often do not correlate tightly with the above outcome tools, but may need to form part of Phase 3 trial measures.

Guidelines for the conduct of clinical trials for spinal cord injury as developed by the ICCP panel: spontaneous recovery after spinal cord injury and statistical power needed for therapeutic clinical trials.

The International Campaign for Cures of Spinal Cord Injury Paralysis (ICCP) supported an international panel tasked with reviewing the methodology for clinical trials in spinal cord injury (SCI), and making recommendations on the conduct of future trials. This is the first of four papers. Here, we examine the spontaneous rate of recovery after SCI and resulting consequences for achieving statistically significant results in clinical trials. We have reanalysed data from the Sygen trial to provide some of this information. Almost all people living with SCI show some recovery of motor function below the initial spinal injury level. While the spontaneous recovery of motor function in patients with motor-complete SCI is fairly limited and predictable, recovery in incomplete SCI patients (American spinal injury Association impairment scale (AIS) C and AIS D) is both more substantial and highly variable. With motor complete lesions (AIS A/AIS B) the majority of functional return is within the zone of partial preservation, and may be sufficient to reclassify the injury level to a lower spinal level. The vast majority of recovery occurs in the first 3 months, but a small amount can persist for up to 18 months or longer. Some sensory recovery occurs after SCI, on roughly the same time course as motor recovery. Based on previous data of the magnitude of spontaneous recovery after SCI, as measured by changes in ASIA motor scores, power calculations suggest that the number of subjects required to achieve a significant result from a trial declines considerably as the start of the study is delayed after SCI. Trials of treatments that are most efficacious when given soon after injury will therefore, require larger patient numbers than trials of treatments that are effective at later time points. As AIS B patients show greater spontaneous recovery than AIS A patients, the number of AIS A patients requiring to be enrolled into a trial is lower. This factor will have to be balanced against the possibility that some treatments will be more effective in incomplete patients. Trials involving motor incomplete SCI patients, or trials where an accurate assessment of AIS grade cannot be made before the start of the trial, will require large subject numbers and/or better objective assessment methods.

The benefits of powered liposuction versus traditional liposuction: a paired comparison analysis.

BACKGROUND: There is much debate about the safety of liposuction as well as the efficacy and risk:benefit ratio of newer devices used in this procedure. OBJECTIVE: To determine if there are any benefits in terms of safety and efficacy of power reciprocating cannulas compared to traditional manual liposuction cannulas. METHODS: Patients served as their own controls in a paired comparison analysis of power liposuction cannulas and traditional liposuction cannulas. RESULTS: Power cannulas significantly reduced procedure times, intraoperative pain, and surgeon fatigue, and increased the amount of fat aspirated per minute. Power cannulas also decreased postoperative pain, ecchymoses, and edema, as well as resulting in higher patient satisfaction scores. CONCLUSION: Power liposuction cannulas produce significantly faster recovery times for patients, allow faster procedure times, and reduce surgeon fatigue, resulting in safer and more precise surgery. A lower incidence of touch-up procedures is likely due to these benefits.

Dermal peels.

Dermal chemical peeling is a very satisfying procedure for patients and physicians alike. Although not providing the ablation of deep wrinkles and scars that dermabrasion and laser procedures may accomplish, trichloroacetic acid peels usually result in few complications and rapid recovery. Patients can usually expect photographic improvement in their skin. The results are usually long lasting, and most patients do not need to repeat dermal peels for at least 2 years. Of all resurfacing procedures, dermal peeling provides the best benefit-to-risk ratio.

The efficacy of powered liposuction.

BACKGROUND: Powered liposuction is a relatively new innovation for more efficient removal of adipose tissue. OBJECTIVE: To evaluate the effectiveness of powered liposuction in removing adipose tissue when compared to traditional liposuction. METHODS: Four powered liposuction devices were evaluated in the power on mode vs. the power off. The fat extracted in each of these modes was measured in a mucous specimen trap. RESULTS: There was increased fat extraction in the powered mode for all instruments. The increased rate of fat extraction varied from 20 to 45% between instruments. the overall increased extraction in powered vs. nonpowered mode was 30%. CONCLUSION: The powered liposuction devices tested significantly increase the efficacy of subcutaneous fat removal during liposuction.

HIV lipodystrophy: review of the syndrome and report of a case treated with liposuction.

BACKGROUND: A syndrome characterized by loss of fat on the face and limbs, localized fatty deposits on the trunk, and metabolic disturbances is becoming increasingly recognized in the human immunodeficiency virus (HIV) patient population. OBJECTIVE: To increase awareness of this syndrome among dermatologists and dermatologic surgeons and to review its various treatment options, including liposuction. METHODS: We present a patient with HIV lipodystrophy syndrome who underwent tumescent liposuction. We also describe our experience with liposuction in the management of this condition and review the treatment options that have been proposed in the literature. RESULTS: In the medical management of HIV lipodystrophy, various agents have been utilized but most have yielded disappointing results. Preliminary evidence on the use of tumescent liposuction in these patients suggests that significant improvement in the cosmetic disfigurement can be achieved. CONCLUSION: This syndrome is common among HIV-infected patients and remains difficult to treat. Although medical therapy may be preferable in most patients, liposuction represents a viable option in selected individuals.

Recruitment and early treatment in a multicenter study of acute spinal cord injury.

STUDY DESIGN: Post hoc secondary analysis of data from 1992 to 1998 in the trial of Sygen in Acute Spinal Cord Injury. OBJECTIVES: Quasi-epidemiologic understanding of injury and treatment patterns and of recruitment in an SCI trial. No drug efficacy results. SUMMARY OF BACKGROUND DATA: The most recent large epidemiologic study was the National SCI Database by Stover and colleagues around 1980. METHODS: Emphasis on descriptive, rather than inferential, statistics: consistent with secondary analysis. RESULTS: The study involved 760 patients at 28 centers in North America. Cervical injuries were more common than thoracic, and complete injuries were more common than incomplete injuries. Recruitment in the complete cervical stratum was 332, but the incomplete thoracic strata had only 31 patients combined. Vital signs at arrival and on randomization show fair stability. Clock times show more injuries on weekends and nights but suggest immediate attention was given. Elapsed times to treatment (especially EMT and Medevac arrival) are short. The rate of direct admission to tertiary centers, traction weight, and time to surgery vary among centers. Inpatient rehabilitation appeared driven by insurance in addition to severity. CONCLUSIONS: The imbalances in favor of cervical and of complete injuries would make it hard for studies to attain results for SCI in general. The vital signs and time patterns suggest local protocol-driven stabilization to prevent secondary physiologic injury early after SCI. Some features of care vary among centers, but the sparseness of prospective data in specific injury and treatment categories suggests that treatment guidelines have limited empirical support and should be made cautiously.

Measurements and recovery patterns in a multicenter study of acute spinal cord injury.

STUDY DESIGN: Post hoc, secondary analysis of data from 1992 to 1998 in the trial of Sygen in acute spinal cord injury. OBJECTIVES: Quasi-epidemiologic understanding of measurement tools and of recovery patterns. No drug efficacy results. SUMMARY OF BACKGROUND DATA: Many authors have studied individual scales for measuring the severity of spinal cord injury. METHODS: Emphasis on descriptive, rather than inferential, statistics: consistent with secondary analysis. RESULTS: Of the 760 patients, 43 died within 365 days. The rate was higher for complete injuries (7.1% vs. 3.2%, P = 0.017). Marked recovery at 26 weeks was more frequent in those with better baseline American Spinal Injury Association (ASIA) Impairment Scale (AIS) scores, but was not different for methylprednisolone within versus after 3 hours. Light touch scores improved at each visit, more so in those with higher scores at baseline. Bladder control similarly improved. Motor and sensory scores exhibited departures from assumptions underlying normal-theory statistical techniques: t test and analysis of variance. Furthermore, they were mixtures of differing distributions from different study strata, so that overall conclusions depend on the mixture of patients seen. CONCLUSIONS: The prognosis of these patients with spinal cord injury seen at 28 centers in North America during the mid-1990s appears better than was often assumed earlier. The general patterns are similar across different measurement scales, although there are intriguing differences. The patterns in different strata are different in specifics, and complete injuries do less well. Pooling data from different strata may result in probability distributions that depart from normal-theory assumptions and give misleading results depending on recruitment patterns.

The Sygen multicenter acute spinal cord injury study.

STUDY DESIGN: Randomized, double-blind, sequential, multicenter clinical trial of two doses of Sygen versus placebo. OBJECTIVES: To determine efficacy and safety of Sygen in acute spinal cord injury. SUMMARY OF BACKGROUND DATA: An earlier, single-center trial in 28 patients showed an improvement (50.0% vs. 7.1%, P = 0.034) in marked recovery with Sygen. METHODS: Standard clinical trial techniques. RESULTS: The prospectively planned analysis at the prespecified endpoint time for all patients was negative. There was a significant effect in all patients in the primary outcome variable (the percentage of marked recovery) at week 8, the end of the dosing period. There was a significant effect in all patients in the time at which marked recovery is first achieved. Restricted to severity Group B, which has small sample size, the primary efficacy analysis showed a trend but did not reach significance. There is a large, consistent and, at some time points, significant effect in the primary outcome variable in the nonoperated patients through week 26. The American Spinal Injury Association motor, light touch, and pinprick scores showed a consistent trend in favor of Sygen, as also did bowel function, bladder function, sacral sensation, and anal contraction. The less severely injured patients appeared to have a greater beneficial drug effect. Evidence against an effect of Sygen was minimal and scattered. CONCLUSIONS: Although not proven in the primary efficacy analysis of this trial, Sygen appears to be beneficial in patients with severe spinal cord injury.

When one liter does not equal 1000 milliliters: implications for the tumescent technique.

BACKGROUND: Tumescent anesthesia has revolutionized the practice of liposuction. Inherent to the tumescent technique is the use of large volumes of dilute solutions of lidocaine with epinephrine instilled into subcutaneous fat deposits. Precise formulation of the tumescent anesthesia is essential to liposuction technique. OBJECTIVES: To determine the actual volumes of fluids contained in intravenous (IV) 1 L bags of saline used for tumescent anesthesia, to calculate volumes supplied in 50 cc stock solutions of 1% lidocaine, and to measure the amount of fluid retained by peristalic pump tubing used for infiltration. METHODS: The amount of saline contained in fifteen 1 L saline bags from three different manufacturers was calculated using graduated cylinder methodology. The volume of tumescent anesthesia retained by peristaltic pump tubing was calculated by expelling the contents of the filler tubing and measuring it. The actual amount of 1% lidocaine contained within fifteen 50 ml "stock" 1% lidocaine bottles from different manufacturers and with different lot numbers was calculated by transferring the contents into graduated cylinders. RESULTS: One liter IV bags of physiologic saline contained an average volume of 1051 ml (range 1033-1069 ml). The 50 ml bottles of 1% lidocaine with epinephrine contain an average of 54 ml of anesthetic (range 52.5-55 ml). Infusion tubing for use with peristaltic pumps may retain 46-146 ml of tumescent anesthesia. CONCLUSION: One liter IV bags of normal saline contain more than 1 L, having an average volume of 1051 ml. Common methods of preparation of 0.05% lidocaine with 1:1,000,000 epinephrine and sodium bicarbonate can increase the total amount of fluid in the tumescent anesthesia to 1112 ml for 0.05% solutions and preparation of a 0.1% solution contains an average volume of 1162 ml. The fluid contained in each bag may be increased over labeling by as much as 11-16%. Final concentrations of lidocaine in tumescent anesthesia may be reduced due to extra fluids. A 0.05% lidocaine solution may have a final lidocaine concentration of 0.045% and a 0.1% lidocaine solution may have an actual concentration of 0.086%. Lidocaine concentrations may be reduced by as much as 10-14%. Extra anesthesia fluid is also contained within stock 50 ml bottles of 1% lidocaine. Dermatologic surgeons should be aware of extra fluid possibly contained within tumescent anesthetic preparation, be aware of the extra anesthesia supplied in standard 1% lidocaine bottles, and possible decreased concentration of lidocaine within the final tumescent anesthesia.

A critical appraisal of the reporting of the National Acute Spinal Cord Injury Studies (II and III) of methylprednisolone in acute spinal cord injury.

From the beginning, the reporting of the results of National Acute Spinal Cord Injury Studies (NASCIS) II and III has been incomplete, leaving clinicians in the spinal cord injury (SCI) community to use or avoid using methylprednisolone in acute SCI on the basis of faith rather than a publicly developed scientific consensus. NASCIS II was initially reported by National Institutes of Health announcements, National Institutes of Health facsimiles to emergency room physicians, and the news media. The subsequent report in the New England Journal of Medicine implied that there was a positive result in the primary efficacy analysis for the entire 487 patient sample. However, this analysis was in fact negative, and the positive result was found only in a secondary analysis of the subgroup of patients who received treatment within 8 hours. In addition, that subgroup apparently had only 62 patients taking methylprednisolone and 67 receiving placebo. The NASCIS II and III reports embody specific choices of statistical methods that have strongly shaped the reporting of results but have not been adequately challenged or or even explained. These studies show statistical artifacts that call their results into question. In NASCIS II, the placebo group treated before 8 hours did poorly, not only when compared with the methylprednisolone group treated before 8 hours but even when compared with the placebo group treated after 8 hours. Thus, the positive result may have been caused by a weakness in the control group rather than any strength of methylprednisolone. In NASCIS III, a randomization imbalance occurred that allocated a disproportionate number of patients with no motor deficit (and therefore no chance for recovery) to the lower dose control group. When this imbalance is controlled for, much of the superiority of the higher dose group seems to disappear. The NASCIS group's decision to admit persons with minor SCIs with minimal or no motor deficit not only enables statistical artifacts it complicates the interpretation of results from the population actually sampled. Perhaps one half of the NASCIS III sample may have had at most a minor deficit. Thus, we do not know whether the results of these studies reflect the severely injured population to which they have been applied. The numbers, tables, and figures in the published reports are scant and are inconsistently defined, making it impossible even for professional statisticians to duplicate the analyses, to guess the effect of changes in assumptions, or to supply the missing parts of the picture. Nonetheless, even 9 years after NASCIS II, the primary data have not been made public. The reporting of the NASCIS studies has fallen far short of the guidelines of the ICH/FDA and of the Evidence-based Medicine Group. Despite the lucrative "off label" markets for methylprednisolone in SCI, no Food and Drug Association indication has been obtained. There has been no public process of validation. These shortcomings have denied physicians the chance to use confidently a drug that many were enthusiastic about and has left them in an intolerably ambiguous position in their therapeutic choices, in their legal exposure, and in their ability to perform further research to help their patients.

Powered liposuction.

BACKGROUND: Although Arpad and Giorgio Fischer initially employed blades within cannulas in their early research while inventing liposuction, hollow cannulas have become the standard instrument for this procedure for the last quarter century. Ultrasonic liposuction was developed in the 1990s to facilitate the passage of cannulas through subcutaneous tissue while liquefying fat. However, these instruments had a number of drawbacks including seromas and tissue burns. Powered cannulas were introduced in 1995 by Gross for "liposhaving." This technique was used on the neck with open surgery under direct observation. OBJECTIVE: Based on these principles, a new powered liposuction device has been designed for body liposuction. METHOD: An oscillating blade within a cannula facilitates removal of fat, especially in fibrous areas such as male flanks and breasts. This instrument has proven to be safe in numerous body areas. Powered reciprocating cannulas also have been recently introduced. These simulate the "to and fro" motion of manual liposuction and appear to be safe. CONCLUSION: Powered liposuction may provide the advantages of ultrasonic liposuction with fewer complications.