Author Correction: Stretching Reduces Tumor Growth in a Mouse Breast Cancer Model.

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Stretching Reduces Tumor Growth in a Mouse Breast Cancer Model.

There is growing interest in developing non-pharmacological treatments that could boost natural defenses against cancer and contribute to primary and secondary cancer prevention. Recent studies have shown that gentle daily stretching for 10 minutes can reduce local connective tissue inflammation and fibrosis. Because mechanical factors within the stroma can influence the tumor microenvironment, we hypothesized that stretching would reduce the growth of tumors implanted within locally stretched tissues and tested this hypothesis in a mouse orthotopic breast cancer model. Female FVB mice (N = 66) underwent bilateral injection of p53/PTEN double-null primary mouse mammary tumor cells into the third mammary fat pad. Mice were randomized to stretch vs. no stretch, and treated for 10 minutes once a day, for four weeks. Tumor volume at end-point was 52% smaller in the stretch group, compared to the no-stretch group (p < 0.001) in the absence of any other treatment. Cytotoxic immune responses were activated and levels of Specialized Pro-Resolving Mediators were elevated in the stretch group. These results suggest a link between immune exhaustion, inflammation resolution and tumor growth. Stretching is a gentle, non-pharmacological intervention that could become an important component of cancer treatment and prevention.

Early genetic restoration of lubricin expression in transgenic mice mitigates chondrocyte peroxynitrite release and caspase-3 activation.

OBJECTIVE: This study investigated the ability of endogenous lubricin secretion to restore joint health following a brief <21 day, postnatal lubricin-null state, in a C57BL/6J Prg4 gene trap (GT) mouse under the control of cre-recombinase. Previously we showed that re-expression of lubricin at 21 days was partly restorative of joint lubrication. DESIGN: The tibio-femoral joints of adult C57BL/6J mice containing lubricin, lacking lubricin, and postnatally lacking lubricin until restoration of lubricin expression at 7 days or 14 days of age were evaluated ex vivo. At 8-weeks of age, whole joint coefficient of friction (COF), and caspase-3 activation were measured and the tibial-femoral joints histologically analyzed for degenerative changes, following progressive cyclic loading. The peroxynitrite content of femoral head cartilage from these mice prior to cyclic loading was measured. RESULTS: Mice that underwent gene recombination at 7 and 14 days of age did not reestablish low COF as joint cycling time increased and were histopathologically indistinguishable from the joints of lubricin-null littermates. However, cartilage from tibio-femoral joints that underwent recombination at 7 and 14 days of age had significantly fewer caspase-3 positive cells and significantly reduced peroxynitrite content compared to lubricin-null littermates. CONCLUSIONS: The biological effects of lubricin, which include limiting inflammation via peroxynitrite production and caspase-3 activation, may be achieved without completely restituting low COF. However, fully recapitulating low COF may require undamaged cartilage surfaces or absence of biofouling, which may interfere with the activity of lubricin.

Comparison of micro-CT post-processing methods for evaluating the trabecular bone volume fraction in a rat ACL-transection model.

Trabecular bone volume fraction assessments are likely sensitive to the analysis method and selection of the region of interest. Currently, there are several methods for selecting the region of interest to analyze trabecular bone in animal models of post-traumatic osteoarthritis. The objective of this study was to compare three published methods for determining the trabecular bone volume fraction of the medial tibial epiphyses in ACL transected and contralateral ACL intact knees. Micro-computed tomography images of both knees were obtained five weeks post-operatively and evaluated using three methods: (1) the Whole Compartment Method that captured the entire medial compartment, (2) the centrally located Single Core Method, and (3) the Triplet Core Method that averaged focal locations in the anterior, central, and posterior regions. The Whole Compartment Method detected significant bone loss in the ACL transected knee compared to the ACL intact knee (p<0.001), with a loss of 15.2±3.9%. The Single Core and the Triplet Core Methods detected losses of 7.5±10.5% (p=0.061) and 14.1±13.7%(p=0.01), respectively. Details regarding segmentation methods are important for facilitating comparisons between studies, and for selecting methods to document trabecular bone changes and treatment outcomes. Based on these findings, the Whole Compartment Method is recommended, as it was least variable and more sensitive for detecting differences in the bone volume fraction in the medial compartment.

Calcium phosphate particulates increase friction in the rat knee joint.

OBJECTIVE: Basic calcium phosphate (BCP) particulates are commonly found in cartilage and synovial fluid of osteoarthritis (OA) joints with the amount of BCP correlating with knee OA severity. How cartilage mineralization affects joint degeneration has yet to be determined. The objective of this study was to determine whether BCP in the synovial fluid affects the rat knee joint coefficient of friction (COF). METHODS: The COFs of knees from both hind limbs of four mature male rats were measured post mortem using a pendulum apparatus with an infrared tracking system. The three conditions evaluated were (1) the naïve state, (2) after the injection of 100 µL of phosphate buffered saline (PBS) (sham) and (3) after the injection of 100 µL of a 1 mg/mL BCP suspension. The decrease in the pendulum amplitude (decay) was fit using two friction models: (1) a one parameter Stanton linear decay model and (2) a two parameters combination Stanton linear decay and viscous damping exponential decay model. RESULTS: The COF increased 17.6% after injection of BCP compared to the naïve (P = 0.0012) and 16.0% compared to the saline injected (P = 0.0018) joints as derived from the one parameter model. The COF did not differ between naïve and saline injected joints. Results from the two parameters model showed a similar increase in COF after injection of BCP while the viscous damping was not significantly different between conditions. CONCLUSIONS: The increased joint friction with BCP particulates suggests BCPs may play a role in articular surface degradation and OA development.

Chronic in vivo load alteration induces degenerative changes in the rat tibiofemoral joint.

OBJECTIVE: We investigated the relationship between the magnitude and duration of sustained compressive load alteration and the development of degenerative changes in the rat tibiofemoral joint. METHODS: A varus loading device was attached to the left hind limb of mature rats to apply increased compression to the medial compartment and decreased compression to the lateral compartment of the tibiofemoral joint of either 0% or 100% body weight for 0, 6 or 20 weeks. Compartment-specific assessment of the tibial plateaus included biomechanical measures (articular cartilage aggregate modulus, permeability and Poisson's ratio, and subchondral bone modulus) and histological assessments (articular cartilage, calcified cartilage, and subchondral bone thicknesses, degenerative scoring parameters, and articular cartilage cellularity). RESULTS: Increased compression in the medial compartment produced significant degenerative changes consistent with the development of osteoarthritis (OA) including a progressive decrease in cartilage aggregate modulus (43% and 77% at 6 and 20 weeks), diminished cellularity (38% and 51% at 6 and 20 weeks), and increased histological degeneration. At 20 weeks, medial compartment articular cartilage thickness decreased 30% while subchondral bone thickness increased 32% and subchondral bone modulus increased 99%. Decreased compression in the lateral compartment increased calcified cartilage thickness, diminished region-specific subchondral bone thickness and revealed trends for reduced cellularity and decreased articular cartilage thickness at 20 weeks. CONCLUSIONS: Altered chronic joint loading produced degenerative changes consistent with those observed clinically with the development of OA and may replicate the slow development of non-traumatic OA in which mechanical loads play a primary etiological role.

Tissue modification of the lateral compartment of the tibio-femoral joint following in vivo varus loading in the rat.

This study describes the first application of a varus loading device (VLD) to the rat hind limb to study the role of sustained altered compressive loading and its relationship to the initiation of degenerative changes to the tibio-femoral joint. The VLD applies decreased compressive load to the lateral compartment and increased compressive load to the medial compartment of the tibio-femoral joint in a controlled manner. Mature rats were randomized into one of three groups: unoperated control, 0% (sham), or 80% body weight (BW). Devices were attached to an animal's leg to deliver altered loads of 0% and 80% BW to the experimental knee for 12 weeks. Compartment-specific material properties of the tibial cartilage and subchondral bone were determined using indentation tests. Articular cartilage, calcified cartilage, and subchondral bone thicknesses, articular cartilage cellularity, and degeneration score were determined histologically. Joint tissues were sensitive to 12 weeks of decreased compressive loading in the lateral compartment with articular cartilage thickness decreased in the peripheral region, subchondral bone thickness increased, and cellularity of the midline region decreased in the 80% BW group as compared to the 0% BW group. The medial compartment revealed trends for diminished cellularity and aggregate modulus with increased loading. The rat-VLD model provides a new system to evaluate altered quantified levels of chronic in vivo loading without disruption of the joint capsule while maintaining full use of the knee. These results reveal a greater sensitivity of tissue parameters to decreased loading versus increased loading of 80% BW for 12 weeks in the rat. This model will allow future mechanistic studies that focus on the initiation and progression of degenerative changes with increased exposure in both magnitude and time to altered compressive loads.

Gait alterations in rats following attachment of a device and application of altered knee loading.

Animal models are widely used to study cartilage degeneration. Experimental interventions to alter contact mechanics in articular joints may also affect the loads borne by the leg during gait and consequently affect the overall loading experienced in the joint. In this study, force plate analyses were utilized to measure parameters of gait in the rear legs of adult rats following application of a varus loading device that altered loading in the knee. Adult rats were assigned to Control, Sham, or Loaded groups (n ≥ 4/each). Varus loading devices were surgically attached to rats in the Sham and Loaded groups. In the Loaded group, this device applied a controlled compressive overload to the medial compartment of the knee during periods of engagement. Peak ground reaction forces during walking were recorded for each rear leg of each group. Analyses of variance were used to compare outcomes across groups (Control, Sham, and Loaded), leg (contralateral, experimental) and device status (disengaged, engaged) to determine the effects of surgically attaching the device and applying a compressive overload to the joint with the device. The mean peak vertical force in the experimental leg was reduced to 30% in the Sham group in comparison to the contralateral leg and the Control group, indicating an effect of attaching the device to the leg (p<0.01). No differences were found in ground reaction forces between the Sham and Loaded groups with application of compressive overloads with the device. The significant reduction in vertical force due to the surgical attachment of the varus loading device must be considered and accounted for in future studies.

Seasonal variation in preeclampsia based on timing of conception.

OBJECTIVE: Studies have suggested that the incidence of preeclampsia may be partially dependent on the month or season of delivery. We sought to evaluate whether preeclampsia occurs seasonally in our population and whether the timing of conception or delivery is more strongly associated with risk. METHODS: Between January 1995 and August 2003, we identified 142 primiparous women with singleton pregnancies who met the American College of Obstetricians and Gynecologists' definition for preeclampsia and compared them with 7,762 primiparous control deliveries. We analyzed rates of preeclampsia by individual month and 3-month seasonal blocks based on conception and delivery. Data were analyzed with the chi2 test, and logistic regression and odds ratios were calculated where appropriate. RESULTS: Preeclampsia occurred in 1.8% of singleton primiparous gestations (142/7,904). Cases were younger than controls (26.5 +/- 5.6 versus 28.0 +/- 0 6.0 years, P < .003), of similar race (97% white versus 96% white, P = .69), and equally likely to have a female child (45% versus 48%, P = .41). We found no significant association of month (logistic regression P = .20) of delivery with the risk of preeclampsia. There was a significant association of month (P = .003) of conception with risk of preeclampsia. Conception during the summer months had the highest risk (incidence 2.3%; odds ratio 1.7; 95% confidence limits 1.06, 2.75) compared with spring (incidence 1.4%). Fall (1.7%) and winter (1.6%) conceptions were associated with intermediate rates of preeclampsia. CONCLUSION: We identified a seasonal variation in preeclampsia that appears to be more strongly related to timing of conception than to the timing of delivery. The highest incidence of preeclampsia was associated with conception in the summer months. LEVEL OF EVIDENCE: II-2.

Comparison of the subjective, physiological, and psychomotor effects of atomoxetine and methylphenidate in light drug users.

This study compared the subjective, physiological, and psychomotor effects of atomoxetine and methylphenidate with placebo in healthy volunteers. Sixteen non-dependent light drug users participated in six experimental sessions, receiving placebo, atomoxetine (20, 45 and 90 mg) and methylphenidate (20 and 40 mg) using a double-blind, Latin square design. Subjective drug effects were assessed using Visual Analog Scales (VAS), the Addiction Research Center Inventory (ARCI) and Adjective Rating Scales (ARS). Psychomotor performance was evaluated using the Digit Symbol Substitution Test (DSST). Physiological measures were also collected throughout the sessions. Assessments were conducted before drug administration and 30, 60, 90, 120, 150, 180 and 240 min following dosing. Forty milligrams methylphenidate produced significant increases on the stimulant portions of the VAS and ARS and the benzedrine, amphetamine, morphine-benzedrine and lysergic acid diethylamine (LSD) subscales of the ARCI relative to placebo. Ninety mg atomoxetine was reported to be unpleasurable relative to placebo as indicated by significant increases on the 'bad' and 'sick' portions of the VAS, and on the LSD subscale of the ARCI. Compared with placebo, both methylphenidate doses significantly increased systolic blood pressure (BP) and heart rate (HR). For atomoxetine, 90 mg increased diastolic BP, 45 and 90 mg increased systolic BP, and all three doses increased HR relative to placebo. Neither compound produced significant differences from placebo on DSST performance. These results suggest that atomoxetine does not induce subjective effects similar to methylphenidate and suggest that it is unlikely that atomoxetine will have abuse liability.

Comparison of fetal growth estimates based on birth weight and ultrasound references.

OBJECTIVE: To compare three different methods for modeling fetal weight gain during the third trimester of pregnancy. METHODS: Ultrasound and live birth weight data were used to construct three models for defining fetal growth during the third trimester: longitudinal ultrasound estimates of fetal weight obtained serially at 3-4 week intervals in 50 uncomplicated, well-dated pregnancies between 19 and 40 weeks' gestation; cross-sectional ultrasound estimates of fetal weight obtained from 2018 ultrasound examinations of singleton, non-anomalous fetuses between 24 and 39 weeks' gestation; and cross-sectional birth weight data obtained from 9553 live singleton, non-anomalous neonates between 24 and 43 completed weeks. Analysis was performed by pairwise partial f test to compare regression curves and zeta test for comparison of mean weekly weight gain. A value of p < 0.05 was accepted for significance. RESULTS: Derived regression lines depicting fetal size across gestation were significantly different from each other (f tests, p < 0.05). Estimates of mean fetal weight were significantly different between the three different models at specific gestational ages. Significant weekly variations in fetal weight gain were observed within the raw cross-sectional data sets, both for ultrasound-estimated fetal weight (range 91-278 g/week) and birth weight (65-309 g/week). CONCLUSIONS: Each of the methods used to model normal fetal weight gain in the third trimester defined a distinct pattern of fetal growth. Normal fetal growth, defined longitudinally, was most closely matched by a combination of cross-sectional ultrasound-derived estimated fetal weight in preterm gestation below 34 weeks' gestation and live birth weight at or beyond 34 weeks.

Behavioral economics of human drug self-administration: progressive ratio versus random sequences of response requirements.

Progressive-ratio (PR) schedules have been used widely to examine the relationship between drug consumption and drug price (i.e. demand curves) in the study of the behavioral economics of drug abuse. Sequential effects produced by the increasing response requirements of progressive-ratio schedules might influence the shape of demand curves for drug reinforcers. This study compared progressive ratio schedule and random sequences of ratio requirements, each incremented across sessions in a within-subject design, to determine if they produced similar behavioral economic and traditional measures of reinforcer efficacy. Self-administration of standardized cigarette puffs (70 cc each) was studied with eight smokers. Puffs were available at nine ratio requirements (e.g. 3, 100, 300, 600, 1500, 3000, 6000, 12000, 24000 responses/three puffs), presented in ascending (progressive-ratio schedule) or random sequence across daily sessions. The parameter estimates obtained on measures of reinforcing efficacy (e.g. breakpoint, peak response rates, elasticity of demand) were similar for both methods of incrementing prices. We found no evidence that PR and random sequences of fixed-ratio (FR) schedules, incremented across daily sessions, resulted in different demand curves.

Effects of infusion rate of intravenously administered morphine on physiological, psychomotor, and self-reported measures in humans.

Although the rate of onset of a drug effect is commonly believed to contribute to a drug's abuse liability, only a few systematic experimental studies have been conducted examining this notion. The present study determined the profile of physiological, psychomotor, and self-reported effects of infusion rate (a key means of manipulating onset of drug action) of intravenously administered morphine, the prototypical analgesic with a known abuse liability in human participants. Two doses of morphine sulfate (5 and 10 mg/70 kg, i.v.) and a placebo dose (0 mg/70 kg, i.v.) were administered to healthy volunteers under three infusion rates (2 min bolus, 15 min, and 60 min). Faster infusions of morphine produced greater positive subjective effects than slower infusions on visual analog scale measures of good drug effect, drug liking, and high. Faster infusions also resulted in greater self-reported drug effects and opioid agonist effects, without producing significant physiological or psychomotor impairment. Importantly, faster rates of drug infusion produced significantly higher morphine plasma levels than slower rates, and morphine plasma levels followed a similar pattern and timing of peak effect as the self-reported effects of the drug. Moreover, morphine produced dose-dependent increases in self-reported drug effects, opioid agonist effects, and morphine plasma levels in the study. Results suggest that the pharmacokinetic properties of a drug, including the dosage administered and the rate of at which it is administered may function to jointly affect the abuse liability of the drug.

Biomechanical response to acupuncture needling in humans.

During acupuncture treatments, acupuncture needles are manipulated to elicit the characteristic "de qi" reaction widely viewed as essential to acupuncture's therapeutic effect. De qi has a biomechanical component, "needle grasp," which we have quantified by measuring the force necessary to pull an acupuncture needle out of the skin (pullout force) in 60 human subjects. We hypothesized that pullout force is greater with both bidirectional needle rotation (BI) and unidirectional rotation (UNI) than no rotation (NO). Acupuncture needles were inserted, manipulated, and pulled out by using a computer-controlled acupuncture needling instrument at eight acupuncture points and eight control points. We found 167 and 52% increases in mean pullout force with UNI and BI, respectively, compared with NO (repeated-measures ANOVA, P < 0.001). Pullout force was on average 18% greater at acupuncture points than at control points (P < 0.001). Needle grasp is therefore a measurable biomechanical phenomenon associated with acupuncture needle manipulation.

Sensitivity of nicotine-containing and de-nicotinized cigarette consumption to alternative non-drug reinforcement: a behavioral economic analysis.

A previous report from our laboratory showed similar measures of reinforcing efficacy for nicotine-containing and de-nicotinized cigarettes when each cigarette type was presented alone. The present experiment further compared the reinforcing efficacy of nicotine-containing and de-nicotinized cigarettes by assessing the effects of alternative non-drug reinforcement on self-administration of both cigarette types. Eight human subjects responded on a progressive-ratio schedule in which the number of plunger pulls required for standardized cigarette puffs increased across sessions. Responding for the two types of cigarette was examined when each was available alone and when the concurrent opportunity to earn money was available. Consumption of nicotine-containing and de-nicotinized cigarettes was decreased by both increases in price and by the concurrent availability of money. The two cigarettes types did not differ in their sensitivity to price or alternative non-drug reinforcement. These results replicate our previous report of similar measures of reinforcing efficacy for the two cigarette types when each was presented alone, and extend our previous findings to a choice situation involving an alternative non-drug reinforcer. These data suggest the importance of further examination of non-pharmacological variables in the maintenance of drug taking and the sensitivity of drug taking to alternative non-drug sources of reinforcement. Factors potentially contributing to the maintenance of smoking the de-nicotinized cigarettes (i.e. conditioned reinforcement, primary reinforcement by respiratory stimulation, instructional control, demand characteristics) are also discussed.

Limits to buprenorphine dosing: a comparison between quintuple and sextuple the maintenance dose every 5 days.

The relative efficacy of quintuple and sextuple buprenorphine dosing in abating withdrawal symptoms for 120 h was compared in opioid-dependent outpatients. Fourteen subjects received buprenorphine in a double-blind, placebo-controlled, cross-over design. Daily sublingual maintenance doses were 4 mg/70 kg (n=4) and 8 mg/70 kg (n=10). After a stabilization period of daily maintenance administration, subjects received quintuple (5x daily maintenance dose) and sextuple (6x daily maintenance dose) doses every 120 h. Measures of opioid agonist and withdrawal effects were assessed daily. Subjective ratings of withdrawal were significantly greater than baseline ratings beyond 96-h post dosing under both regimens. There was no evidence, however, that those subjective ratings of withdrawal differed between the two regimens. Thus, these data suggest that sextuple buprenorphine dosing, administered every 5 days, does not abate opioid-withdrawal beyond 96 hours.

Examining the limits of the buprenorphine interdosing interval: daily, every-third-day and every-fifth-day dosing regimens.

AIMS: Opioid-dependent outpatients may be more likely to present for pharmacological treatment if less than daily dosing can be arranged. These studies compared opioid withdrawal symptoms during 24-, 72-, and 120-hour buprenorphine dosing regimens and evaluated participants' preferences for these different dosing regimens. PARTICIPANTS: Thirty-three opioid-dependent participants received daily sublingual maintenance doses of 4 mg/70 kg (n = 14) or 8 mg/70 kg (n = 19) of liquid buprenorphine. METHODS: In Study I participants received, in a random order, three dosing regimens for five repetitions of each: daily maintenance doses every 24 hours (4 or 8 mg/70 kg), triple the daily maintenance dose every 72 hours (12 or 24 mg/70 kg) and quintuple the daily maintenance dose every 120 hours (20 or 40 mg/70 kg). Doses were administered under double-blind procedures, and placebos were administered on the interposed days during the latter two regimens. Subjective and observer ratings of opioid withdrawal symptoms were assessed daily prior to receipt of each dose. In Study II, a new group of participants received each of the three dosing regimens under open-dosing procedures and then chose between the different dosing regimens. FINDINGS: Opioid withdrawal symptoms increased significantly during the every-fifth-day dosing regimen in both the blind- and open-dosing studies. In the choice phase of Study II, only one participant (7%) chose quintuple-every-fifth-day dosing over all other dosing options. CONCLUSIONS: These results suggest that the maximum duration of action of buprenorphine is less than 5 days when five times the daily maintenance dose is provided.

Plasma volume expansion in early pregnancy.

OBJECTIVE: To determine the time course of plasma volume expansion in early pregnancy. METHODS: We prospectively measured plasma volume by Evans blue dye dilution during the menstrual (cycle day 2--3), follicular (cycle day 9--10), and luteal phases (cycle day urinary leutinizing hormone [LH] surge plus 9--10) of the menstrual cycle and at three additional time points (LH surge + 16 days, LH surge + 28 days, and LH surge + 70 days) in women achieving pregnancy. Twenty-one subjects were examined during 38 menstrual cycles to establish baseline menstrual cycle data. Ten subjects conceived within 1 year of menstrual cycle studies. All ten pregnancies were viable and reached the third trimester. Analyses used repeated-measures analysis of variance with P <.05 accepted for significance. RESULTS: Mean plasma volume was found to change significantly across the period of observation (P <.008) in those who conceived. Plasma volume at LH surge + 70 days (12 menstrual weeks, 2320 +/- 280 mL) was greater than either menstrual cycle estimates or early pregnancy estimates of plasma volume. There was no difference in plasma volume at LH surge + 16 days (2077 +/- 288 mL) or LH surge + 28 days (2010 +/- 271 mL) compared with menstrual cycle measurements during the menstrual phase (2156 +/- 292 mL), follicular phase (2036 +/- 280 mL), and luteal phase (2120 +/- 425 mL). There was no significant difference between those who conceived and those who did not in their mean menstrual cycle plasma volume. CONCLUSION: Plasma volume expansion in early human pregnancy cannot be identified until after the sixth menstrual week. By 12 menstrual weeks, plasma volume has expanded by approximately 14% +/- 12% (mean +/- SD) over follicular phase measurements.

Alcohol dependence among cocaine-dependent outpatients: demographics, drug use, treatment outcome and other characteristics.

OBJECTIVE: Concurrent dependence on alcohol is common among those seeking treatment for cocaine dependence. More information is needed about differences between those with and without concurrent alcohol dependence, including possible special treatment needs or outcome differences. METHOD: Data were obtained from 302 adults (70% men) enrolled in outpatient treatment for cocaine dependence. Individuals who did and those who did not meet criteria for alcohol dependence were compared on demographics, drug use, treatment outcome and other variables. RESULTS: With regard to cocaine use, alcoholics were more likely than nonalcoholics to report an intranasal route of administration, use of cocaine in social settings, more simultaneous use of cocaine and alcohol, and more adverse consequences of their cocaine use. With regard to alcohol use, alcoholics reported consuming alcohol more frequently and in larger amounts, had longer drinking histories and were more likely than nonalcoholics to report increases in alcohol consumption when using cocaine. Alcoholics were heavier cigarette smokers than nonalcoholics and reported more severe employment, legal, family and psychiatric problems. There were overall improvements in both groups from intake through 12 months after treatment. With regard to treatment retention and cocaine abstinence, alcoholics had better outcomes than nonalcoholics when treated with intensive behavioral counseling plus incentives, but the reverse was true when treated with control treatments. CONCLUSIONS: Compared with nonalcoholic cocaine-dependent subjects, codependent patients exhibit a wider array of problems, many of which merit professional attention. Both alcoholics and nonalcoholics exhibit substantial improvements during treatment, with alcoholics perhaps requiring extra treatment efforts for successful outcomes.

Do pediatric trauma centers have better survival rates than adult trauma centers? An examination of the National Pediatric Trauma Registry.

BACKGROUND: Pediatric trauma centers (PTCs) were developed to improve the survival of injured children, but it is currently unknown if children admitted to PTCs are more likely to survive than those admitted to adult trauma centers (ATCs). METHODS: Fifty-three thousand one hundred thirteen pediatric trauma cases from 22 PTCs and 31 ATCs included in the National Pediatric Trauma Registry were reviewed to evaluate survival rates at PTCs and ATCs. RESULTS: Overall, 1,259 children died. The raw mortality rate was lower at PTCs (1.81% of 32,554 children) than at ATCs (3.88% of 18,368 children). However, patients admitted to ATCs were more severely injured. When Injury Severity Score, Pediatric Trauma Score, mechanism (blunt or penetrating), gender, age, clustering, and American College of Surgeons (ACS) verification status were controlled for using a single logistic regression model, there was no statistically significant difference in survival between PTCs and ATCs (odds ratio, 1.02; 95% confidence interval, 0.83-1.26; p = 0.587). A similar comparison of the 12 ACS-verified trauma centers with the 41 nonverified centers showed verification to be associated with improved survival (odds ratio, 0.75; 95% confidence interval, 0.58-0.97; p = 0.013). CONCLUSION: Although PTCs have higher overall survival rates than ATCs, this difference disappears when the analysis controls for Injury Severity Score, Pediatric Trauma Score, age, mechanism, and ACS verification status. ACS-verified centers have significantly higher survival rates than do unverified centers.