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The purpose of this study was to determine if the co-ingestion of carbohydrate (CHO) with branched-chain amino acids (BCAA) or l-leucine (LEU) preferentially affected serum IGF-1 and the expression of myogenic-related genes in response to resistance exercise (RE). Forty-one college-age males were randomly assigned to 1 of 4 groups: CHO, CHO-BCAA, CHO-LEU, or placebo (PLC). Resistance exercise consisted of 4 sets of 10 repetitions of leg press and leg extension at 80 % 1RM. Supplements were ingested peri-exercise, and venous blood and muscle biopsies were obtained pre-exercise (PRE), and at 30, 120, and 360 min post-exercise. Serum IGF-1 was determined with ELISA, and skeletal muscle mRNA expression of myostatin, ACTRIIB, p21kip, p27kip, CDK2, cyclin B1, cyclin D1, Myo-D, myogenin, MRF-4, and myf5 was determined using real-time PCR. Results were analyzed by two-way ANOVA for serum IGF-1 and two-way MANOVA for mRNA expression. Serum IGF-1 in CHO + BCAA was greater than PLC ( p < 0.05) but was not affected by RE ( p > 0.05). A significant group × time interaction was located for cylin D1 ( p < 0.05), but not for any other genes. However, significant time effects were noted for cyclin B1 and p21cip ( p < 0.05). At 30, 120 and 360 min post-exercise, p21cip was significantly less than PRE. Cyclin D1 was greater than PRE and 30 min post-exercise at 120 and 360 min post-exercise, whereas cyclin B1 was significantly greater than PRE at 120 min post-exercise ( p < 0.05). Unlike the co-ingestion of CHO with either BCAA or l-leucine in conjunction with RE, the expression of various myogenically related genes were up-regulated with RE. [ABSTRACT FROM AUTHOR]

Abstract: Background: A number of diet and exercise programs purport to help promote and maintain weight loss. However, few studies have compared the efficacy of different methods. Objective: To determine whether adherence to a meal-replacement–based diet program (MRP) with encouragement to increase physical activity is as effective as following a more structured meal-plan–based diet and supervised exercise program (SDE) in sedentary obese women. Design: Randomized comparative effectiveness trial. Participants/setting: From July 2007 to October 2008, 90 obese and apparently healthy women completed a 10-week university-based weight loss trial while 77 women from this cohort also completed a 24-week weight maintenance phase. Intervention: Participants were matched and randomized to participate in an MRP or SDE program. Main outcome measures: Weight loss, health, and fitness-related data were assessed at 0 and 10 weeks on all subjects as well as at 14, 22, and 34 weeks on participants who completed the weight maintenance phase. Statistical analyses performed: Data were analyzed by multivariate analysis of variance for repeated measures. Results: During the 10-week weight loss phase, moderate and vigorous physical activity levels were significantly higher in the SDE group with no differences observed between groups in daily energy intake. The SDE group lost more weight (−3.1±3.7 vs −1.6±2.5 kg; P=0.03); fat mass (−2.3±3.5 vs −0.9±1.6 kg; P=0.02); centimeters from the hips (−4.6±7 vs −0.2±6 cm; P=0.002) and waist (−2.9±6 vs −0.6±5 cm; P=0.05); and, experienced a greater increase in peak aerobic capacity than participants in the MRP group. During the 24-week maintenance phase, participants in the SDE group maintained greater moderate and vigorous physical activity levels, weight loss, fat loss, and saw greater improvement in maximal aerobic capacity and strength. Conclusions: In sedentary and obese women, an SDE-based program appears to be more efficacious in promoting and maintaining weight loss and improvements in markers of health and fitness compared to an MRP type program with encouragement to increase physical activity. [Copyright &y& Elsevier]

The article reports on research conducted to examine the effects creatine monohydrate supplementation with and without D-pinitol had on resistance training adaptations. Researchers evaluated 24 male resistance trained athletes. They found that adding D-pinitol to creatine monohydrate does not appear to facilitate further physiological adaptations while resistance training and that creatine monohydrate supplementation helps to improve strength and body composition while resistance training

This research sought to examine how exercise-related affective states compared with average daily affect. To answer this question, this investigation combined naturalistic methods (i.e., experience sampling) with a more typical exercise protocol. Participants were 36 university students enrolled in step aerobics classes. Participants were asked to carry Palm data recorders set to randomly cue them to complete a questionnaire to tap the affective dimensions of arousal (AD ACL; Thayer, 1989) five times per day over a 7-day period. In addition, participants were asked to complete the AD ACL immediately before, at the midpoint of exercise, and after a 15-min cool-down period after engaging in a bout of aerobic exercise in a class setting. Intensity of exercise was self-chosen, and mean intensity was "strong" (M = 5.28, SD = 1.73) based on Borg's 10-item RPE scale. Daily affect, based on the mean of experience sampling points, and preexercise scores were significantly different for the tension and tiredness subscales. Tension and tiredness were greater during daily recordings than during the preexercise baseline. Results suggest that researchers may be underestimating the tension- and tiredness-reducing effects of exercise if this finding is replicable. The limitations of this research, such as possible contamination by diurnal variations in affective states, are considered. [ABSTRACT FROM AUTHOR]

Abstract: Objective: We evaluated whether colostrum (Col) or an isocaloric and isonitrogenous blend of whey and casein in addition to creatine (Cr) affects body composition, muscular strength and endurance, and anaerobic performance during resistance training. Methods: Forty-nine resistance-trained subjects participated in a standardized 12-wk total body resistance training program. In a double-blind and randomized manner, subjects supplemented their diet with a protein control (Pro), Pro/Col, Pro/Cr, or Col/Cr. Supplements were isocaloric and isonitrogenous and provided 60 g/d of casein/whey (Pro) or Col as the protein source. At 0, 8, and 12 wk of supplementation, subjects were weighed, had body composition determined using dual-energy X-ray absorptiometry (DXA), performed one-repetition maximum (1RM) and 80% of 1RM tests on the bench press and leg press, and 30-s anaerobic sprint capacity tests. Data (mean ± SD) were analyzed by repeated measures analysis of variance and reported as raw data in all tables and as changes from baseline for all figures for the Pro, Pro/Col, Pro/Cr, and Col/Cr groups, respectively. Results: Resistance training increased 1RM strength, muscular endurance, and anaerobic sprint capacity equally in all groups. Significant main and interaction effects (P < 0.05) were found for body mass, DXA total scanned mass, and fat-free mass (FFM; lean plus bone), whereas no changes (P > 0.05) were noted for fat mass, percent fat, or bone content. Post hoc analysis showed that, compared with Pro, subjects ingesting Pro/Col, Pro/Cr, and Col/Cr showed greater gains in body mass and DXA total scanned mass. Subjects ingesting Pro/Cr and Col/Cr had greater increases in FFM during training in comparison with Pro/Col. Conclusion: In conjunction with 12 wk of resistance training, ingestion of Col or a blend of whey and casein protein with a vitamin/mineral supplement containing Cr resulted in greater improvements in FFM in comparison with Pro and Pro/Col. [Copyright &y& Elsevier]

Background: For more than 20 years, tamoxifen has been the mainstay of adjuvant endocrine therapy for women with hormone-sensitive early-stage breast cancer. However, not only does tamoxifen have potential side-effects such as an increased risk of endometrial cancer and thromboembolic events, but patients can also develop resistance to the drug. We aimed to investigate whether switching treatment of postmenopausal women with such breast cancer to anastrozole after 2-3 years of tamoxifen would be more effective than continuing on tamoxifen for a total of 5 years.Methods: We did a meta-analysis of three clinical trials--the Austrian Breast and Colorectal Cancer Study Group (ABCSG 8), Arimidex-Nolvadex (ARNO 95), and the Italian Tamoxifen Anastrozole (ITA) studies--in which postmenopausal women with histologically confirmed, hormone-sensitive early-stage breast cancer were randomised to 1 mg/day anastrozole (n=2009) after 2-3 years of tamoxifen treatment or to continued 20 or 30 mg/day tamoxifen (n=1997). We analysed the data with a stratified Cox proportional hazards model with the covariates of age, tumour size, nodal status, grade, surgery, and chemotherapy.Findings: Patients who switched to anastrozole had fewer disease recurrences (92 vs 159) and deaths (66 vs 90) than did those who remained on tamoxifen, resulting in significant improvements in disease-free survival (hazard ratio 0.59 [95% CI 0.48-0.74]; p<0.0001), event-free survival (0.55 [0.42-0.71]; p<0.0001), distant recurrence-free survival (0.61 [0.45-0.83]; p=0.002), and overall survival (0.71 [0.52-0.98]; p=0.04).Interpretation: Our results show that the clinical benefits in terms of event-free survival seen in individual trials for those patients who switched to anastrozole translate into a benefit in overall survival. These findings confirm that clinicians should consider switching postmenopausal women who have taken adjuvant tamoxifen for 2-3 years to anastrozole. [ABSTRACT FROM AUTHOR]

Abstract: Objective: We evaluated the pharmacokinetics, safety, and efficacy of l-arginine α-ketoglutarate (AAKG) in trained adult men. Methods: Subjects participated in two studies that employed a randomized, double-blind, controlled design. In study 1, 10 healthy men (30–50 y old) fasted for 8 h and then ingested 4 g of time-released or non–timed-released AAKG. Blood samples were taken for 8 h after AAKG ingestion to assess the pharmacokinetic profile of l-arginine. After 1 wk the alternative supplement was ingested. In study 2, which was placebo controlled, 35 resistance-trained adult men (30–50 y old) were randomly assigned to ingest 4 g of AAKG (three times a day, i.e., 12 g daily, n = 20) or placebo (n = 15). Participants performed 4 d of periodized resistance training per week for 8 wk. At 0, 4, and 8 wk of supplementation the following tests were performed: clinical blood markers, one repetition maximum bench press, isokinetic quadriceps muscle endurance, anaerobic power, aerobic capacity, total body water, body composition, and psychometric parameters tests. Data were analyzed by repeated measures analysis of variance. Results: In study 1, significant differences were observed in plasma arginine levels in subjects taking non–timed-release and timed-release AAKG. In study 2, significant differences were observed in the AAKG group (P < 0.05) for 1RM bench press, Wingate peak power, blood glucose, and plasma arginine. No significant differences were observed between groups in body composition, total body water, isokinetic quadriceps muscle endurance, or aerobic capacity. Conclusion: AAKG supplementation appeared to be safe and well tolerated, and positively influenced 1RM bench press and Wingate peak power performance. AAKG did not influence body composition or aerobic capacity. [Copyright &y& Elsevier]

The purpose of this study was to investigate the movement speed characteristics of 2 intrinsically different limbs. Twenty subjects volunteered to participate (10 men and 10 women). Each subject performed 5 repetitions of concentric knee and elbow extension and flexion movements at 60 through 500 d·s-1 on an isokinetic dynamometer. Kinematic data were collected at 1,000 Hz and separated into rate of velocity development (RVD) and peak torque. Results demonstrated a significant (p < 0.05) main effect for sex for RVD and peak torque. Significant (p < 0.05) differences were also demonstrated between knee and elbow RVD and between knee and elbow peak torque at every speed tested. Neither knee and elbow RVD nor peak torque demonstrated any significant Pearson correlations at any speed tested (r = 20.17-0.41). These results collectively point to the specificity of limb speed and torque as a result of biophysical differences such as length and mass. Therefore, strength and speed may be modulated by neuromotor patterns that differ based on individual limbs. [ABSTRACT FROM AUTHOR]

Triplet regimens containing immunomodulatory drugs and proteasome inhibitors (PIs) have improved outcomes and extended survival for patients with relapsed/refractory multiple myeloma (RRMM). We evaluated updated health-related quality of life (HRQoL) findings from the phase 2 ELOQUENT-3 clinical trial (NCT02654132) after 4 years of treatment with elotuzumab plus pomalidomide and dexamethasone (EPd) and assessed the impact of the addition of elotuzumab on patients' HRQoL. HRQoL was assessed as an exploratory endpoint using the MD Anderson Symptom Inventory for Multiple Myeloma (MDASI-MM), which evaluates symptom severity, symptom interference, and HRQoL, and the 3-level EQ-5D, a patient-reported measure of health utility and general health. Statistical analyses included descriptive responder, longitudinal mixed-model, and time-to-first-deterioration (TTD) analyses using prespecified minimally important differences and responder definitions. Of 117 randomized patients, 106 (EPd, n = 55; pomalidomide and dexamethasone [Pd], n = 51) were eligible for inclusion in HRQoL analyses. Completion rates at almost all on-treatment visits were ≥80%. The proportion of patients treated with EPd who improved or maintained stable HRQoL until cycle 13 ranged from 82% to 96% for MDASI-MM total symptom score and 64% to 85% for MDASI-MM symptom interference. Across measurements, there were no clinically meaningful differences in changes from baseline between treatment arms, and TTD was not significantly different for EPd versus Pd. In conclusion, HRQoL was not impacted by the addition of elotuzumab to Pd and did not significantly deteriorate in patients with RRMM previously treated with lenalidomide and a PI in ELOQUENT-3., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association.)

Background: We previously reported that consuming a food bar (FB) containing whey protein and the plant fiber isomalto-oligosaccharides [IMO] had a lower glycemic (GI) but similar insulinemic response as a high GI carbohydrate. Therefore, we hypothesized that ingestion of this FB before, during, and following intense exercise would better maintain glucose homeostasis and performance while hastening recovery in comparison to the common practice of ingesting carbohydrate alone., Methods: Twelve resistance-trained males participated in an open label, randomized, counterbalanced, crossover trial with a 7-d washout period. Participants consumed a carbohydrate matched dextrose comparitor (CHO) or a FB containing 20 g of whey, 25 g of IMO, and 7 g of fat 30-min before, mid-way, and following intense exercise. Participants performed 11 resistance-exercises (3 sets of 10 repetitions at 70% of 1RM) followed by agility and sprint conditioning drills for time. Participants donated blood to assess catabolic and inflammatory markers, performed isokinetic strength tests, and rated perceptions of muscle soreness, hypoglycemia before, and following exercise and after 48 h of recovery. Data were analyzed using general linear models (GLM) for repeated measures and mean changes from baseline with 95% confidence intervals (CI) with a one-way analysis of variance. Data are reported as mean change from baseline with 95% CI., Results: GLM analysis demonstrated that blood glucose was significantly higher 30-min post-ingestion for CHO (3.1 [2.0, 4.3 mmol/L,] and FB (0.8 [0.2, 1.5, mmol/L, p = 0.001) while the post-exercise ratio of insulin to glucose was greater with FB (CHO 0.04 [0.00, 0.08], FB 0.11 [0.07, 0.15], p = 0.013, η 2  = 0.25). GLM analysis revealed no significant interaction effects between treatments in lifting volume of each resistance-exercise or total lifting volume. However, analysis of mean changes from baseline with 95% CI's revealed that leg press lifting volume (CHO -130.79 [- 235.02, - 26.55]; FB -7.94 [- 112.17, 96.30] kg, p = 0.09, η 2  = 0.12) and total lifting volume (CHO -198.26 [- 320.1, - 76.4], FB -81.7 [- 203.6, 40.1] kg, p = 0.175, η 2  = 0.08) from set 1 to 3 was significantly reduced for CHO, but not for the FB. No significant interaction effects were observed in ratings of muscle soreness. However, mean change analysis revealed that ratings of soreness of the distal vastus medialis significantly increased from baseline with CHO while being unchanged with FB (CHO 1.88 [0.60, 3.17]; FB 0.29 [- 0.99, 1.57] cm, p = 0.083, η 2  = 0.13). No significant GLM interaction or mean change analysis effects were seen between treatments in sprint performance, isokinetic strength, markers of catabolism, stress and sex hormones, or inflammatory markers., Conclusion: Pilot study results provide some evidence that ingestion of this FB can positively affect glucose homeostasis, help maintain workout performance, and lessen perceptions of muscle soreness., Trial Registration: clinicaltrials.gov, # NCT03704337 . Retrospectively registered 12, July 2018.

Background: Sports nutrition is a constantly evolving field with hundreds of research papers published annually. In the year 2017 alone, 2082 articles were published under the key words 'sport nutrition'. Consequently, staying current with the relevant literature is often difficult., Methods: This paper is an ongoing update of the sports nutrition review article originally published as the lead paper to launch the Journal of the International Society of Sports Nutrition in 2004 and updated in 2010. It presents a well-referenced overview of the current state of the science related to optimization of training and performance enhancement through exercise training and nutrition. Notably, due to the accelerated pace and size at which the literature base in this research area grows, the topics discussed will focus on muscle hypertrophy and performance enhancement. As such, this paper provides an overview of: 1.) How ergogenic aids and dietary supplements are defined in terms of governmental regulation and oversight; 2.) How dietary supplements are legally regulated in the United States; 3.) How to evaluate the scientific merit of nutritional supplements; 4.) General nutritional strategies to optimize performance and enhance recovery; and, 5.) An overview of our current understanding of nutritional approaches to augment skeletal muscle hypertrophy and the potential ergogenic value of various dietary and supplemental approaches., Conclusions: This updated review is to provide ISSN members and individuals interested in sports nutrition with information that can be implemented in educational, research or practical settings and serve as a foundational basis for determining the efficacy and safety of many common sport nutrition products and their ingredients.

Objectives: OSKIRA-4 evaluated the efficacy of fostamatinib monotherapy versus placebo on the signs and symptoms of rheumatoid arthritis over 6 weeks by Disease Activity Score C reactive protein (DAS-28(CRP)) and assessed non-inferiority to adalimumab monotherapy at Week 24 by DAS-28(CRP)., Methods: Overall, 279 patients not currently taking disease-modifying antirheumatic drugs were randomised to: (A) fostamatinib 100 mg twice daily for 24 weeks plus placebo injection every 2 weeks (PBOI); (B) fostamatinib 100 mg twice daily for 4 weeks, then 150 mg once daily up to Week 24, plus PBOI; (C) fostamatinib 100 mg twice daily for 4 weeks, then 100 mg once daily up to Week 24, plus PBOI; (D) adalimumab 40 mg every 2 weeks for 24 weeks, plus oral placebo twice daily; or (E) oral placebo twice daily for 6 weeks, plus PBOI, then a switch to arm A or B., Results: Fostamatinib demonstrated a significant improvement in DAS-28(CRP) score from baseline versus placebo at Week 6 for arms A and B, but not C. Fostamatinib was significantly less effective than adalimumab at Week 24 based on DAS-28(CRP). Adverse events observed with fostamatinib treatment were consistent with those reported in previous studies, including hypertension and diarrhoea., Conclusions: Fostamatinib demonstrated efficacy as monotherapy, showing superior DAS-28(CRP) score changes between baseline and 6 weeks when compared with placebo in treatment arms A and B. However, all fostamatinib regimens demonstrated inferior responses compared with adalimumab at Week 24., Trial Registration Number: Clinicaltrials.gov: NCT01264770., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Position Statement: The International Society of Sports Nutrition (ISSN) bases the following position stand on a critical analysis of the literature on the safety and efficacy of the use of energy drinks (ED) or energy shots (ES). The ISSN has concluded the following. 1. Although ED and ES contain a number of nutrients that are purported to affect mental and/or physical performance, the primary ergogenic nutrients in most ED and ES appear to be carbohydrate and/or caffeine. 2. The ergogenic value of caffeine on mental and physical performance has been well-established but the potential additive benefits of other nutrients contained in ED and ES remains to be determined. 3. Consuming ED 10-60 minutes before exercise can improve mental focus, alertness, anaerobic performance, and/or endurance performance. 4. Many ED and ES contain numerous ingredients; these products in particular merit further study to demonstrate their safety and potential effects on physical and mental performance. 5. There is some limited evidence that consumption of low-calorie ED during training and/or weight loss trials may provide ergogenic benefit and/or promote a small amount of additional fat loss. However, ingestion of higher calorie ED may promote weight gain if the energy intake from consumption of ED is not carefully considered as part of the total daily energy intake. 6. Athletes should consider the impact of ingesting high glycemic load carbohydrates on metabolic health, blood glucose and insulin levels, as well as the effects of caffeine and other stimulants on motor skill performance. 7. Children and adolescents should only consider use of ED or ES with parental approval after consideration of the amount of carbohydrate, caffeine, and other nutrients contained in the ED or ES and a thorough understanding of the potential side effects. 8. Indiscriminant use of ED or ES, especially if more than one serving per day is consumed, may lead to adverse events and harmful side effects. 9. Diabetics and individuals with pre-existing cardiovascular, metabolic, hepatorenal, and neurologic disease who are taking medications that may be affected by high glycemic load foods, caffeine, and/or other stimulants should avoid use of ED and/or ES unless approved by their physician.

Creatine monohydrate has become one of the most popular ergogenic sport supplements used today. It is a nonessential dietary compound that is both endogenously synthesized and naturally ingested through diet. Creatine ingested through supplementation has been observed to be absorbed into the muscle exclusively by means of a creatine transporter, CreaT1. The major rationale of creatine supplementation is to maximize the increase within the intracellular pool of total creatine (creatine + phosphocreatine). There is much evidence indicating that creatine supplementation can improve athletic performance and cellular bioenergetics, although variability does exist. It is hypothesized that this variability is due to the process that controls both the influx and efflux of creatine across the cell membrane, and is likely due to a decrease in activity of the creatine transporter from various compounding factors. Furthermore, additional data suggests that an individual's initial biological profile may partially determine the efficacy of a creatine supplementation protocol. This brief review will examine both animal and human research in relation to the regulation and expression of the creatine transporter (CreaT). The current literature is very preliminary in regards to examining how creatine supplementation affects CreaT expression while concomitantly following a resistance training regimen. In conclusion, it is prudent that future research begin to examine CreaT expression due to creatine supplementation in humans in much the same way as in animal models.

This study examined the effectiveness of a pre-exercise drink (PRX) called EM.PACT on indices of maximal cardiorespiratory fitness. Twenty-four males (n = 12) and females (n = 12) ages 18-24 years (20.25 + 1.42), volunteered as subjects. Each subject performed two randomized trials of a VO2max treadmill test within a week of each other. Subjects in this randomized, placebo controlled, counter balanced, crossover design, ingested either a placebo (water) or PRX 20 minutes before each exercise bout. VO2max and time to exhaustion (Time) during graded exercise testing were evaluated. Using paired samples t-tests, significantly greater mean values were found in VO2max and Time for the PRX trial compared to the placebo trial (p < .05). Results indicate that indices of cardiorespiratory fitness; specifically VO2max and Time are enhanced by ingestion of PRX prior to exercise testing. The combined results of this investigation may provide meaningful practical applications for coaches and athletes alike regarding ergogenic hydration options.

Objective: We evaluated the effects of calcium pyruvate supplementation during training on body composition and metabolic responses to exercise., Methods: Twenty-three untrained females were matched and assigned to ingest in a double blind and randomized manner either 5 g of calcium pyruvate (PYR) or a placebo (PL) twice daily for 30 d while participating in a supervised exercise program. Prior to and following supplementation, subjects had body composition determined via hydrodensiometry; performed a maximal cardiopulmonary exercise test; and performed a 45-min walk test at 70% of pre-training VO2 max in which fasting pre- and post exercise blood samples determined., Results: No significant differences were observed between groups in energy intake or training volume. Univariate repeated measures ANOVA revealed that subjects in the PYR group gained less weight (PL 1.2 +/- 0.3, PYR 0.3 +/- 0.3 kg, P = 0.04), lost more fat (PL 1.1 +/- 0.5; PYR -0.4 +/- 0.5 kg, P = 0.03), and tended to lose a greater percentage of body fat (PL 1.0 +/- 0.7; PYR -0.65 +/- 0.6%, P = 0.07), with no differences observed in fat-free mass (PL 0.1 +/- 0.5; PYR 0.7 +/- 0.3 kg, P = 0.29). However, these changes were not significant when body composition data were analyzed by MANOVA (P = 0.16). There was some evidence that PYR may negate some of the beneficial effects of exercise on HDL values. No significant differences were observed between groups in maximal exercise responses or metabolic responses to submaximal walking., Conclusions: Results indicate that PYR supplementation during training does not significantly affect body composition or exercise performance and may negatively affect some blood lipid levels.

Background: Quetiapine, a drug with a broad pharmacologic profile (similar to that of clozapine), may show benefits for agitation in patients with psychoses. Also, quetiapine may be superior to placebo and either equal or superior to haloperidol in treating this symptom. Available data for other second-generation antipsychotic agents show that quetiapine may have better efficacy in improving agitation compared with haloperidol., Objective: This reanalysis of a previously reported pivotal clinical trial assessed whether quetiapine or haloperidol has benefits for the treatment of hostility and agitation among patients experiencing an acute exacerbation of schizophrenia., Methods: Patients aged 18 to 65 years of either sex and any ethnicity who had a diagnosis of schizophrenia based on the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition criteria and who were experiencing an acute exacerbation were recruited into the study. A priori, data from patients assigned to 4 therapeutically effective quetiapine treatment groups (150, 300, 600, and 750 mg) in a previously reported 6-week, double-blind, placebo-controlled clinical trial were combined and compared with data from patients given haloperidol 12 mg or placebo on an agitation measure derived from the Brief Psychiatric Rating Scale (BPRS). Patients who received at least 2 weeks of treatment who had a baseline assessment and at least 1 postbaseline assessment after the 2 weeks of treatment were included. An analysis of variance with the baseline hostility score and center as covariates was used to assess treatment effects of quetiapine or haloperidol versus placebo for changes in agitation scores. A path analysis was used to separate the direct from the indirect effects (via improvements in psychoses and/or overall psychopathology) on agitation scores of quetiapine relative to haloperidol., Results: A total of 257 patients (193 men, 64 women) were studied. The combined quetiapine groups comprised 175 patients; the haloperidol group, 42 patients; and the placebo group, 40 patients. Quetiapine treatment reduced agitation scores significantly among patients with acute psychoses compared with placebo. A slight reduction in agitation scores was found when haloperidol treatment was compared with placebo, but this difference was not statistically significant. Compared with haloperidol, quetiapine treatment had a direct and significant effect on agitation that was independent of the improvement in psychotic symptoms., Conclusions: The data in this study suggest that quetiapine treatment has benefits for hostility and agitation among patients experiencing an acute exacerbation of schizophrenia. Furthermore, the path analysis indicated that, relative to haloperidol, quetiapine appeared to have direct effects on agitation that were independent of improvements in psychoses or overall psychopathology, as assessed by the BPRS.