Effects of a short course of eszopiclone on continuous positive airway pressure adherence: a randomized trial.

BACKGROUND: Adherence to short-term continuous positive airway pressure (CPAP) may predict long-term use. Unfortunately, initial CPAP intolerance may lead to poor adherence or abandonment of therapy. OBJECTIVE: To determine whether a short course of eszopiclone at the onset of therapy improves long-term CPAP adherence more than placebo in adults with obstructive sleep apnea. DESIGN: Parallel randomized, placebo-controlled trial from March 2007 to December 2008. Randomization, maintained and concealed centrally by pharmacy personnel, was computer-generated using fixed blocks of 10. Referring physicians, investigators, and patients were blinded to the treatment assignment until after the final data were collected. (ClinicalTrials.gov registration number: NCT00612157). SETTING: Academic sleep disorder center. PATIENTS: 160 adults (mean age, 45.7 years [SD, 7.3]; mean apnea-hypopnea index, 36.9 events/h [SD, 23]) with newly diagnosed obstructive sleep apnea initiating CPAP. INTERVENTION: Eszopiclone, 3 mg (n = 76), or matching placebo (n = 78) for the first 14 nights of CPAP. MEASUREMENTS: Use of CPAP was measured weekly for 24 weeks. Adherence to CPAP (primary outcome) and the rate of CPAP discontinuation and improvements in symptoms (secondary outcomes) were compared. Follow-up at 1, 3, and 6 months was completed by 150, 136, and 120 patients, respectively. RESULTS: Patients in the eszopiclone group used CPAP for 20.8% more nights (95% CI, 7.2% to 34.4%; P = 0.003), 1.3 more hours per night for all nights (CI, 0.4 to 2.2 hours; P = 0.005), and 1.1 more hours per night of CPAP use (CI, 0.2 to 2.1 hours; P = 0.019). The hazard ratio for discontinuation of CPAP was 1.90 (CI, 1.1 to 3.4; P = 0.033) times higher in the placebo group. Side effects were reported in 7.1% of patients and did not differ between groups. LIMITATIONS: Patients had severe obstructive sleep apnea treated at a specialized sleep center with frequent follow-up; results may not be generalizable to different settings. Patients' tolerance to CPAP and their reasons for discontinuation were not assessed. CONCLUSION: Compared with placebo, a short course of eszopiclone during the first 2 weeks of CPAP improved adherence and led to fewer patients discontinuing therapy.

Evolutionary genetics: jumping into a new species.

A new study finds a dramatic increase in transposable element numbers in three new sunflower hybrid species, and may suggest a novel role for transposable elements in speciation.

The genetics of hybrid male sterility between the allopatric species pair Drosophila persimilis and D. pseudoobscura bogotana: dominant sterility alleles in collinear autosomal regions.

F(1) hybrid male sterility is thought to result from interactions between loci on the X chromosome and dominant-acting loci on the autosomes. While X-linked loci that contribute to hybrid male sterility have been precisely localized in many animal taxa, their dominant autosomal interactors have been more difficult to localize precisely and/or have been shown to be of relatively smaller effect. Here, we identified and mapped at least four dominant autosomal factors contributing to hybrid male sterility in the allopatric species pair Drosophila persimilis and D. pseudoobscura bogotana. Using these results, we tested predictions of reduced recombination models of speciation. Consistent with these models, three of the four QTL associated with hybrid male sterility occur in collinear (uninverted) regions of these genomes. Furthermore, these QTL do not contribute significantly to hybrid male sterility in crosses between the sympatric species D. persimilis and D. pseudoobscura pseudoobscura. The autosomal loci identified in this study provide the basis for introgression mapping and, ultimately, for molecular cloning of interacting genes that contribute to F(1) hybrid sterility.

Survey of alcohol use in the U.S. Army.

The objective of this study was to collect data that would provide information about the frequency, attitudes, and consequences of alcohol use in the U.S. Army. A questionnaire was used to assess the frequency of alcohol consumption, attitudes related to the use of alcohol, and adverse consequences experienced with alcohol use. The survey was conducted at Walter Reed Army Medical Center in Washington, D.C. Survey participants included both military employees working at Walter Reed Army Medical Center and military patients. No attempt was made to identify the medical status of the participants. The investigators distributed 1,200 questionnaires. Following distribution, the investigators received 1,010 completed questionnaires, resulting in an 84% return rate. Thirty-four percent of the survey participants (n = 335) were deployed to an area of combat operations. There was a significant difference in binge drinking between military personnel assigned to an area of combat operations and those not assigned to an area of combat operations (p = 0.023). Multiple regression results showed that age, marital status, and deployment status were correlated with four or more drinks at one time (p < 0.001). In other words, binge drinking is more likely to occur among military personnel who are younger, experiencing marital problems, and recently returned from an area of combat operations. Significant differences between the two groups also emerged in terms of other specific consequences associated with consumption. Deployment to an area of combat operations seems to influence consumption patterns, alcohol related attitudes, and behaviors. This could be a consequence of wartime experiences. This study should help guide the clinical screening of alcohol use disorders, which may complicate emotional recovery from traumatic experiences if undetected.

The intravenous ketamine test predicts subsequent response to an oral dextromethorphan treatment regimen in fibromyalgia patients.

UNLABELLED: Fibromyalgia (FM) is a challenging pain syndrome for which no reliable pharmacologic treatment exists. Recent clinical studies suggest that N-methyl-D-aspartate receptors might play a role in the pathogenesis of this disorder. To determine whether an intravenous (IV) ketamine test predicts the response to a therapeutic trial with an oral N-methyl-D-aspartate receptor antagonist, we performed a low-dose (0.1 mg/kg) IV ketamine infusion on 34 consecutive patients with FM, which was subsequently followed by an oral dextromethorphan (DX) treatment regimen. As per previous guidelines, the cutoff value for a positive response to the IV ketamine test was designated to be 67% pain relief, and a positive response to DX treatment was 50% pain reduction at 4- to 6-week follow-up visits. The degree of correlation between pain relief with ketamine and DX was highly significant (Pearson correlation coefficient, 0.66; P < .001). Ten patients responded positively to both ketamine and DX, 19 responded to neither drug, 3 had a positive response to ketamine but not DX, and 2 obtained good pain relief with DX but not ketamine. The sensitivity of the IV ketamine test was 83%, the specificity was 86%, the positive predictive value was 77%, and the negative predictive value was 91%. An association was also found between the development of side effects to the two treatments. PERSPECTIVE: The response to an IV ketamine infusion was found to predict the subsequent response to an oral dextromethorphan treatment regimen in fibromyalgia patients, with an observed agreement of 83%. Considering the refractory nature of fibromyalgia to conventional pain treatments, the IV ketamine test might enhance patient care by saving time and reducing unnecessary treatment trials.

Natural Variation in plep-1 Causes Male-Male Copulatory Behavior in C. elegans.

In sexual species, gametes have to find and recognize one another. Signaling is thus central to sexual reproduction and involves a rapidly evolving interplay of shared and divergent interests [1-4]. Among Caenorhabditis nematodes, three species have evolved self-fertilization, changing the balance of intersexual relations [5]. Males in these androdioecious species are rare, and the evolutionary interests of hermaphrodites dominate. Signaling has shifted accordingly, with females losing behavioral responses to males [6, 7] and males losing competitive abilities [8, 9]. Males in these species also show variable same-sex and autocopulatory mating behaviors [6, 10]. These behaviors could have evolved by relaxed selection on male function, accumulation of sexually antagonistic alleles that benefit hermaphrodites and harm males [5, 11], or neither of these, because androdioecy also reduces the ability of populations to respond to selection [12-14]. We have identified the genetic cause of a male-male mating behavior exhibited by geographically dispersed C. elegans isolates, wherein males mate with and deposit copulatory plugs on one another's excretory pores. We find a single locus of major effect that is explained by segregation of a loss-of-function mutation in an uncharacterized gene, plep-1, expressed in the excretory cell in both sexes. Males homozygous for the plep-1 mutation have excretory pores that are attractive or receptive to copulatory behavior of other males. Excretory pore plugs are injurious and hermaphrodite activity is compromised in plep-1 mutants, so the allele might be unconditionally deleterious, persisting in the population because the species' androdioecious mating system limits the reach of selection.

A prospective study of the incidence of myocarditis/pericarditis and new onset cardiac symptoms following smallpox and influenza vaccination.

BACKGROUND: Although myocarditis/pericarditis (MP) has been identified as an adverse event following smallpox vaccine (SPX), the prospective incidence of this reaction and new onset cardiac symptoms, including possible subclinical injury, has not been prospectively defined. PURPOSE: The study's primary objective was to determine the prospective incidence of new onset cardiac symptoms, clinical and possible subclinical MP in temporal association with immunization. METHODS: New onset cardiac symptoms, clinical MP and cardiac specific troponin T (cTnT) elevations following SPX (above individual baseline values) were measured in a multi-center prospective, active surveillance cohort study of healthy subjects receiving either smallpox vaccine or trivalent influenza vaccine (TIV). RESULTS: New onset chest pain, dyspnea, and/or palpitations occurred in 10.6% of SPX-vaccinees and 2.6% of TIV-vaccinees within 30 days of immunization (relative risk (RR) 4.0, 95% CI: 1.7-9.3). Among the 1081 SPX-vaccinees with complete follow-up, 4 Caucasian males were diagnosed with probable myocarditis and 1 female with suspected pericarditis. This indicates a post-SPX incidence rate more than 200-times higher than the pre-SPX background population surveillance rate of myocarditis/pericarditis (RR 214, 95% CI 65-558). Additionally, 31 SPX-vaccinees without specific cardiac symptoms were found to have over 2-fold increases in cTnT (>99th percentile) from baseline (pre-SPX) during the window of risk for clinical myocarditis/pericarditis and meeting a proposed case definition for possible subclinical myocarditis. This rate is 60-times higher than the incidence rate of overt clinical cases. No clinical or possible subclinical myocarditis cases were identified in the TIV-vaccinated group. CONCLUSIONS: Passive surveillance significantly underestimates the true incidence of myocarditis/pericarditis after smallpox immunization. Evidence of subclinical transient cardiac muscle injury post-vaccinia immunization is a finding that requires further study to include long-term outcomes surveillance. Active safety surveillance is needed to identify adverse events that are not well understood or previously recognized.

Conspecific sperm precedence in sister species of Drosophila with overlapping ranges.

Barriers to gene flow that act after mating but before fertilization are often overlooked in studies of reproductive isolation. Where species are sympatric, such "cryptic" isolating barriers may be important in maintaining species as distinct entities. Drosophila yakuba and its sister species D. santomea have overlapping ranges on the island of São Tomé, off the coast of West Africa. Previous studies have shown that the two species are strongly sexually isolated. However, the degree of sexual isolation observed in the laboratory cannot explain the low frequency (approximately 1%) of hybrids observed in nature. This study identifies two "cryptic" isolating barriers that may further reduce gene flow between D. yakuba and D. santomea where they are sympatric. First, noncompetitive gametic isolation has evolved between D. yakuba and D. santomea: heterospecific matings between the two species produce significantly fewer offspring than do conspecific matings. Second, conspecific sperm precedence (CSP) occurs when D. yakuba females mate with conspecific and heterospecific males. However, CSP is asymmetrical: D. santomea females do not show patterns of sperm usage consistent with CSP. Drosophila yakuba and D. santomea females also differ with respect to remating propensity after first mating with conspecific males. These results suggest that noncompetitive and competitive gametic isolating barriers may contribute to reproductive isolation between D. yakuba and D. santomea.

Sexual isolation between two sibling species with overlapping ranges: Drosophila santomea and Drosophila yakuba.

Drosophila yakuba is widespread in Africa, whereas D. santomea, its newly discovered sister species, is endemic to the volcanic island of São Tomé in the Gulf of Guinea. Drosophila santomea probably formed after colonization of the island by a D. yakuba-like ancestor. The species presently have overlapping ranges on the mountain Pico do São Tomé, with some hybridization occurring in this region. Sexual isolation between the species is uniformly high regardless of the source of the populations, and, as in many pairs of Drosophila species, is asymmetrical, so that hybridizations occur much more readily in one direction than the other. Despite the fact that these species meet many of the conditions required for the evolution of reinforcement (the elevation of sexual isolation by natural selection to avoid maladaptive interspecific hybridization), there is no evidence that sexual isolation between the species is highest in the zone of overlap. Sexual isolation is due to evolutionary changes in both female preference for heterospecific males and in the vigor with which males court heterospecific females. Heterospecific matings are also slower to take place than are homospecific matings, constituting another possible form of reproductive isolation. Genetic studies show that, when tested with females of either species, male hybrids having a D. santomea X chromosome mate much less frequently with females of either species than do males having a D. yakuba X chromosome, suggesting that the interaction between the D. santomea X chromosome and the D. yakuba genome causes behavioral sterility. Hybrid F1 females mate readily with males of either species, so that sexual isolation in this sex is completely recessive, a phenomenon seen in other Drosophila species. There has also been significant evolutionary change in the duration of copulation between these species; this difference involves genetic changes in both sexes, with at least two genes responsible in males and at least one in females.

The causes of false-positive medial branch (facet joint) blocks in soldiers and retirees.

OBJECTIVE: The purpose of this study was to determine the factors associated with false-positive medial branch blocks (MBB), the nerve blocks used to diagnose facet arthropathy, in soldiers and retirees. METHODS: The study subjects were 78 patients with chronic low back pain who underwent diagnostic MBB to determine whether or not the facet joints were pain generators. Radiofrequency denervation of these nerves was performed in all patients with positive responses. Patients who failed to obtain pain relief after the blocks (negative blocks) and those who obtained temporary pain relief after MBB but failed radiofrequency denervation (false-positive blocks) then proceeded to undergo discography. Based on patients' responses to diagnostic blocks, discography results, the presence of radicular pain, and previous back surgery, the data were analyzed to determine whether any of these variables correlated with false-positive MBB. RESULTS: The presence of discogenic or radicular pain was not associated with a higher false-positive response rate to MBB. Conversely, the absence of discogenic pain was associated with a higher percentage of false-positive blocks. There was also a trend for patients with previous back surgery to have a higher false-positive rate than those who had not undergone previous surgery. CONCLUSIONS: Although a high incidence of epidural and foraminal spread occurs during the performance of MBB, this is unlikely to be a significant cause of false-positive blocks.

Clinical application of ethyl glucuronide testing in the U.S. Army.

This study examined the clinical characteristics of ethyl glucuronide testing among service members referred to a military substance abuse program. The authors analyzed 1,852 urine specimens from 328 service members collected over a two year period. Among all participants, approximately one-fifth (n = 45/262, 17.2%) produced a positive ethyl glucuronide result at the initial assessment. Nearly two-thirds (n = 29/45, 64%) of the service members who initially tested positive had at least one additional positive specimen during the next five sequential tests. A statistically significant decline (p = 0.017) in ethyl glucuronide levels occurred with serial testing over time. The authors suggest that ethyl glucuronide testing can join with other risk mitigation strategies to help reduce alcohol-related adverse incidents.

Epistasis modifies the dominance of loci causing hybrid male sterility in the Drosophila pseudoobscura species group.

Speciation, the evolution of reproductive isolation between populations, serves as the driving force for generating biodiversity. Postzygotic barriers to gene flow, such as F(1) hybrid sterility and inviability, play important roles in the establishment and maintenance of biological species. F(1) hybrid incompatibilities in taxa that obey Haldane's rule, the observation that the heterogametic sex suffers greater hybrid fitness problems than the homogametic sex, are thought to often result from interactions between recessive-acting X-linked loci and dominant-acting autosomal loci. Because they play such prominent roles in producing hybrid incompatibilities, we examine the dominance and nature of epistasis between alleles derived from Drosophila persimilis that confer hybrid male sterility in the genetic background of its sister species, D. pseudoobscura bogotana. We show that epistasis elevates the apparent dominance of individually recessive-acting QTL such that they can contribute to F(1) hybrid sterility. These results have important implications for assumptions underlying theoretical models of hybrid incompatibilities and may offer a possible explanation for why, to date, identification of dominant-acting autosomal "speciation genes" has been challenging.

Epistasis among Drosophila persimilis factors conferring hybrid male sterility with D. pseudoobscura bogotana.

The Bateson-Dobzhansky-Muller model posits that hybrid incompatibilities result from genetic changes that accumulate during population divergence. Indeed, much effort in recent years has been devoted to identifying genes associated with hybrid incompatibilities, often with limited success, suggesting that hybrid sterility and inviability are frequently caused by complex interactions between multiple loci and not by single or a small number of gene pairs. Our previous study showed that the nature of epistasis between sterility-conferring QTL in the Drosophila persimilis-D. pseudoobscura bogotana species pair is highly specific. Here, we further dissect one of the three QTL underlying hybrid male sterility between these species and provide evidence for multiple factors within this QTL. This result indicates that the number of loci thought to contribute to hybrid dysfunction may have been underestimated, and we discuss how linkage and complex epistasis may be characteristic of the genetics of hybrid incompatibilities. We further pinpoint the location of one locus that confers hybrid male sterility when homozygous, dubbed "mule-like", to roughly 250 kilobases.

The effect of vein repair on the risk of venous thromboembolic events: a review of more than 100 traumatic military venous injuries.

BACKGROUND: The management of venous trauma remains controversial. Critics of venous repair have cited an increased incidence of associated venous thromboembolic events with this management. We analyzed the current treatment of wartime venous injuries in United States military personnel in an effort to answer this question. METHODS: From December 1, 2001, to October 31, 2005, all United States casualties with named venous injuries were evaluated. A retrospective review of a clinical database was performed on demographics, mechanism of injury, associated injuries, treatment, outcomes, and venous thromboembolic events. Data were analyzed using the Fisher exact test, analysis of variance, and logarithmic transformation. RESULTS: During this 5-year period, 82 patients sustained 103 named venous injuries due to combat operations. All patients were male, with an average age of 27.9 years (range, 20.3-58.3 years). Blast injuries accounted for 54 venous injuries (65.9%), gunshot wounds for 25 (30.5%), and motor vehicle accidents for 3 (3.6%). The venous injury was isolated in 28 patients (34.1%), and 16 (19.5%) had multiple venous injuries. The venous injury in two patients was associated with acute phlegmasia, with fractures in 33 (40.2%), and 22 (28.1%) sustained neurologic deficits. Venous injuries were treated by ligation in 65 patients (63.1%) and by open surgical repair in 38 (36.9%). Postoperative extremity edema occurred in all patients irrespective of method of management. Thrombosis after venous repair occurred in six of the 38 cases (15.8%). Pulmonary emboli developed in three patients, one after open repair and two after ligation (P > .99). CONCLUSION: In the largest review of military venous trauma in more than three decades, we found no difference in the incidence of venous thromboembolic complications between venous injuries managed by open repair vs ligation. Blast injuries of the extremities have caused most of the venous injuries. Ligation is the most common modality of treatment in combat zones. Long-term morbidity associated with venous injuries and their management will be assessed in future follow-up studies.

Gender differences and alcohol use in the US Army.

CONTEXT: Operation Iraqi Freedom offered an opportunity to study the role of alcohol use among men and women serving in the US Army. The goal of this study was to determine whether there are gender-based differences in alcohol use among US Army soldiers, and if so, to evaluate the role of alcohol education efforts in the military. METHODS: In February 2005, 1200 individuals enlisted in the US Army were asked to complete a 29-item questionnaire regarding alcohol-use patterns. Survey topics included attitudes toward alcohol consumption and associated negative consequences. RESULTS: Six hundred eighty-five men and 325 women (N=1010) responded to the questionnaire for an overall response rate of 84%. Although men were more likely to engage in "bolus" drinking (ie, binge drinking), women exceeded established guidelines for safe alcohol consumption at a risk-adjusted rate nearly twice that of men. In addition, for individuals whose behaviors were not in conformity with public health guidelines for safe alcohol consumption, the severity of reported negative consequences was influenced by gender. Women initially experience greater psychosocial impairment, and-should harmful drinking patterns progress to alcohol dependency-they are at greater risk of injury, morbidity, and mortality than men. CONCLUSION: Several gender-specific differences in alcohol-consumption patterns were found. Because the present study also found that women generally have more interest in educational interventions for alcohol abuse issues, however, researchers conclude that the efficacy of US Army risk-reduction programs would be improved by addressing gender-based differences.

A survey of alcohol consumption among first-year military medical students.

First-year medical students (n = 138) at the U.S. Military's Medical School report frequent binge drinking. Nearly one fifth of female and one third of male students report at least one episode of binge drinking in the two weeks preceding a survey of alcohol use. Only one fifth of the medical students reported an interest in an expanded addiction medicine curriculum. The authors' promoted the use of a survey to bridge the gap between self assessment and learning.

A recombinational portrait of the Drosophila pseudoobscura genome.

Drosophila pseudoobscura has been intensively studied by evolutionary biologists for over 70 years. The recent publication of the genome sequence not only permits studies of comparative genomics with other dipterans but also opens the door to identifying genes associated with adaptive traits or speciation or testing for the signature of natural selection across the genome. Information on regional rates of recombination, localization of inversion breakpoints distinguishing it from its sibling species D. persimilis, and known polymorphic markers may be useful in such studies. Here, we present a molecular linkage map of four of the five major chromosome arms of D. pseudoobscura. In doing so, we order and orient several sequence contig groups, localize the inversion breakpoints on chromosome 2 to intervals of 200 kilobases, and identify one error in the published sequence assembly. Our results show that regional recombination rates in D. pseudoobscura are much higher than in D. melanogaster and significantly higher even than in D. persimilis. Furthermore, we detect a non-significant positive correlation between recombination rate and published DNA sequence variation. Finally, the online Appendix presents 200 primer sequence pairs for molecular markers that can be used for mapping of quantitative trait loci, of which 125 are known to be polymorphic within or between species.

What imaging studies are necessary for abdominal aortic endograft sizing? A prospective blinded study using conventional computed tomography, aortography, and three-dimensional computed tomography.

OBJECTIVE: Preoperative imaging modalities for endovascular abdominal aortic aneurysm repair (EVAR) include conventional computed tomography (CT), aortography with a marking catheter, and three-dimensional computed tomography (3D CT). Although each technique has advantages, to date no study has compared in a prospective manner the reproducibility of measurements and impact on graft selection of all three modalities. The objective of this study was to determine the most useful imaging studies in planning EVAR. METHODS: Twenty patients being considered for EVAR were enrolled prospectively to undergo a conventional CT scan and aortography. The CT scans were then reconstructed into 3D images using Preview Treatment Planning Software (Medical Media Systems, West Lebanon, NH). Four measurements of diameter and six of length were made from each modality in determining the proper graft for EVAR. RESULTS: Measurements from all three modalities were reproducible with intraobserver correlation coefficients of 0.79 to 1.0 for aortography, 0.87 to 1.0 for CT, and 0.96 to 1.0 for 3D CT. Measurements between observers were also similar from each modality; interobserver correlations were 0.70 to 0.97 for aortography, 0.76 to 0.97 for CT, and 0.73 to 0.99 for 3D CT. Significant differences ( P < .01) in diameter measurements were noted at D2 with aortography compared with 3D CT, whereas differences in length measurements were found between CT and 3D CT at L4 (nonaneurysmal right iliac) ( P < .01). The correlation between CT and 3D CT for most length measurements was acceptable (0.63 to 1.0). Aortography for diameters correlated poorly (0.35 to 0.67) with 3D CT. When the endograft selected by aortography/CT or 3D CT alone was compared with the actual endograft used, there was agreement in 11 of 11 patients when adjusted for +/- one size in diameter or length. CONCLUSION: Reproducible and comparable measures of diameter and length can be obtained by each of three imaging modalities available for endograft sizing. As a single imaging modality, 3D CT appears to have the best correlation for both diameters and lengths; however, the difference is not sufficient enough to alter endograft selection. Three-dimensional CT may be reserved for challenging aortic anatomy where small differences in measurements would affect patient or graft selection for EVAR.

The intravenous ketamine test: a predictive response tool for oral dextromethorphan treatment in neuropathic pain.

IV infusion tests performed to predict subsequent response to oral analgesics are an increasingly popular method used to enhance medical care and conserve resources. Because no infusion test is completely accurate, the potential benefits of these tests must be weighed against the frustration and waste in resources encountered with false-positive results, and the failure to use a potentially beneficial treatment with false-negative results. In recent years, drugs that act antagonistically at N-methyl-d-aspartate receptors have been shown to be valuable adjuncts in the treatment of pain. To determine the predictive value of small-dose (0.1 mg/kg) IV ketamine on an oral dextromethorphan (DX) treatment regimen, we analyzed the analgesic response to these drugs in 25 patients at 2 tertiary care military treatment facilities, institutions at which DX is not readily accessible. When >/=50% response for both drugs was used as the outcome measure for success, the positive predictive value of the ketamine test was 64%, the negative predictive value 73%, and the observed agreement 68%. However, when >/=67% relief with ketamine was used as an outcome measure (as determined by a receiver operating characteristic curve), the positive predictive value was 90%, the negative predictive value 80%, and the observed agreement increased to 84%. Based on these results, we conclude that an IV ketamine test may be useful in predicting response to oral DX. More research is needed to determine the ideal candidates for such a test, and the optimal dose and cutoff value for the response to ketamine.

Probing for thoracic pedicle screw tract violation(s): is it valid?

BACKGROUND: Preparation of the thoracic pedicle screw tract is a critical step prior to the placement of screws. The ability to detect pedicle wall violation(s) by probing prior to insertion of thoracic pedicles screws, however, has not been studied. The purpose of this study was to evaluate the inter- and intraobserver agreement and the accuracy in detecting thoracic pedicle screw tract violation(s) among surgeons at various levels of training. METHODS: With use of a straightforward trajectory, under direct visualization, 108 thoracic pedicle screw tracts (54 cadaveric thoracic vertebrae) were prepared in a standard fashion, followed by tapping with a 4.5-mm cannulated tap. A deliberate pedicle violation was randomly created by an independent investigator in either the anterior, the medial, or the lateral wall in 65 pedicles. Following this, four blinded, independent surgeons at various levels of training probed the specimens on three separate occasions to determine if a breach was present (1,296 discrete data points). Surgeon findings were then recorded as breach present or absent and, if present, breach location. The Cohen kappa correlation coefficient (kappa a) and 95% confidence interval were used to assess the accuracy of the observers and the inter- and intraobserver agreement. RESULTS: The mean accuracy over three iterations, the validity in detecting the breach location, and the intraobserver agreement varied by level of training and experience, with the most experienced observer (observer 1) scoring the best and the least experienced observer (observer 4) scoring the worst. The three most senior surgeons had good intraobserver agreement. Interobserver agreement was low between the four observers. CONCLUSIONS: An observer's ability to accurately detect the presence or absence of a pedicle tract violation and the breach location, if present, is dependent on the surgeon's level of training. Probing the pedicle tract prior to placement of pedicle screws in the thoracic spine is likely a learned skill that improves with repetition and experience.