A phase II multicenter study of the anti-CD19 antibody drug conjugate coltuximab ravtansine (SAR3419) in patients with relapsed or refractory diffuse large B-cell lymphoma previously treated with rituximab-based immunotherapy.

This phase II, single-arm, multicenter study examined the efficacy and safety of coltuximab ravtansine (an anti-CD19 antibody drug conjugate) in 61 patients with histologically documented (de novo or transformed) relapsed or refractory diffuse large B-cell lymphoma who had previously received rituximab-containing immuno-chemotherapy. Patients had received a median of 2.0 (range 0-9) prior treatment regimens for diffuse large B-cell lymphoma and almost half (45.9%) had bulky disease (≥1 lesion >5 cm) at trial entry. Patients received coltuximab ravtansine (55 mg/m2) in 4 weekly and 4 biweekly administrations until disease progression or unacceptable toxicity. Forty-one patients were eligible for inclusion in the per protocol population. Overall response rate (International Working Group criteria) in the per protocol population, the primary end point, was 18/41 [43.9%; 90% confidence interval (CI:) 30.6-57.9%]. Median duration of response, progression-free survival, and overall survival (all treated patients) were 4.7 (range 0.0-8.8) months, 4.4 (90%CI: 3.02-5.78) months, and 9.2 (90%CI: 6.57-12.09) months, respectively. Common non-hematologic adverse events included asthenia/fatigue (30%), nausea (23%), and diarrhea (20%). Grade 3-4 adverse events were reported in 23 patients (38%), the most frequent being hepatotoxicity (3%) and abdominal pain (3%). Eye disorders occurred in 15 patients (25%); all were grade 1-2 and none required a dose modification. Coltuximab ravtansine monotherapy was well tolerated and resulted in moderate clinical responses in pre-treated patients with relapsed/refractory diffuse large B-cell lymphoma. (Registered at: clinicaltrials.gov identifier: 01472887).

Long-term outcomes, secondary malignancies and stem cell collection following bendamustine in patients with previously treated non-Hodgkin lymphoma.

Despite the long history of bendamustine as treatment for indolent non-Hodgkin lymphoma, long-term efficacy and toxicity data are minimal. We reviewed long-term data from three clinical trials to characterize the toxicity and efficacy of patients receiving bendamustine. Data were available for 149 subjects at 21 sites. The median age was 60 years at the start of bendamustine (range 39-84), and patients had received a median of 3 prior therapies. The histologies included grades 1-2 follicular lymphoma (FL; n = 73), grade 3 FL (n = 23), small lymphocytic lymphoma (n = 20), marginal zone lymphoma (n = 15), mantle cell lymphoma (n = 9), transformed lymphomas (n = 5), lymphoplasmacytic lymphoma (n = 2) and not reported (n = 2). The median event-free survival was 14·1 months. Nine of 12 attempted stem cell collections were successful. With a median follow-up of 8·9 years, 23 patients developed 25 cancers, including 8 patients with myelodysplastic syndrome/acute myeloid leukaemia. These data provide important information regarding the long-term toxicity of bendamustine in previously treated patients. A small but meaningful number of patients achieved durable remissions following bendamustine. These rigorously collected, patient-level, long-term follow-up data provide reassurance that bendamustine or bendamustine plus rituximab is associated with efficacy and safety for patients with relapsed or refractory indolent non-Hodgkin lymphoma.

The Effect of Interchange Rotation Period and Number on Australian Football Running Performance.

Montgomery, PG, and Wisbey, B. The effect of interchange rotation period and number on Australian Football running performance. J Strength Cond Res 30(7): 1890-1897, 2016-To determine the effect of on-field rotation periods and total number of game rotations on Australian Football running performance, elite Australian Football players (n = 21, mean ± SD; 23.2 ± 1.7 years; 183.5 ± 3.7 cm; 83.2 ± 4.5 kg) had Global Positioning System game data from 22 rounds divided into a total of 692 on-field playing periods. These periods were allocated into time blocks of 2:00-minute increments, with the log transformed percentage differences in running performance (m·min) between blocks analyzed by effect size and meaningful differences. A total of 7,730 game rotation and associated average m·min combinations collected over 3 Australian Football seasons were also assessed by effect size and meaningful differences. Running capacity decreases after 5:00 minutes by ∼3% for each 2:00 minutes of on-field time up to 9:00 minutes, with variable responses between positions up to 6.7% for nomadic players. For each rotation less than 6 per game, clear small-to-moderate decreases up to 3.6% in running capacity occurred per rotation. To maintain a high level of running capacity, shorter on-field periods are more effective in Australian Football; however, players and coaches should be aware that with interchange restriction, slightly longer on-field periods achieve similar results.

Validation of heart rate monitor-based predictions of oxygen uptake and energy expenditure.

To validate VO2 and energy expenditure predictions by the Suunto heart rate (HR) system against a first principle gas analysis system, well-trained male (n = 10, age 29.8 +/- 4.3 years, VO2 65.9 +/- 9.7 ml x kg x min) and female (n = 7, 25.6 +/- 3.6 years, 57.0 +/- 4.2 ml x kg x min) runners completed a 2-stage incremental running test to establish submaximal and maximal oxygen uptake values. Metabolic cart values were used as the criterion measure of VO2 and energy expenditure (kJ) and compared with the predicted values from the Suunto software. The 3 levels of software analysis for the Suunto system were basic personal information (BI), BI + measured maximal HR (BIhr), and BIhr + measured VO2 (BIhr + v). Comparisons were analyzed using linear regression to determine the standard error of the estimate (SEE). Eight subjects repeated the trial within 7 days to determine reliability (typical error [TE]). The SEEs for oxygen consumption via BI, BIhr, and BIhr + v were 2.6, 2.8, and 2.6 ml.kg.min, respectively, with corresponding percent coefficient of variation (%CV) of 6.0, 6.5, and 6.0. The bias compared with the criterion VO2 decreased from -6.3 for BI, -2.5 for BIhr, to -0.9% for BIhr + v. The SEE of energy expenditure improved from BI (6.74 kJ) to BIhr (6.56) and BIhr + v (6.14) with corresponding %CV of 13.6, 12.2, and 12.7. The TE values for VO2 were approximately 0.60 ml x kg x min and approximately 2 kJ for energy expenditure. The %CV for VO2 and energy expenditure was approximately 1 to 4%. Although reliable, basic HR-based estimations of VO2 and energy expenditure from the Suunto system underestimated VO2 and energy expenditure by approximately 6 and 13%, respectively. However, estimation can be improved when maximal HR and VO2 values are added to the software analysis.

Premedication to reduce discomfort during screening mammography.

PURPOSE: To test the hypothesis that premedication with acetaminophen, ibuprofen, and/or 4% lidocaine gel would decrease discomfort and improve satisfaction with screening mammography in women who expect a higher level of discomfort. MATERIALS AND METHODS: In this HIPAA-compliant, institutional review board-approved, prospective, double-blinded, placebo-controlled clinical trial, 418 women aged 32-89 years who expected substantial discomfort with screening mammography were randomly divided to receive premedication with acetaminophen, ibuprofen, and/or 4% lidocaine gel. Subjects provided informed written consent. The primary outcome was discomfort. Secondary outcomes were satisfaction and plans for future mammography on the basis of discomfort. Subjects completed structured questionnaires with visual analog scales to measure discomfort and satisfaction. A generalized linear mixed-models framework was used to assess the effect of medications on discomfort during mammography, and satisfaction with technologist and machine combinations was included as a random effect. The "plans for mammography next year" outcome was modeled by using a binary distribution and logit link function. RESULTS: Discomfort was significantly lower in the lidocaine gel group (P = .01). Satisfaction was significantly negatively correlated with discomfort (P < .001). Satisfaction and whether or not the subject had delayed her mammography because of fear of discomfort had significant effects on plans to undergo mammography next year (P < .001 for both). There were significant differences in discomfort between different combinations of technologists and machines. CONCLUSION: Premedication with 4% lidocaine gel significantly reduced discomfort during screening mammography, and reduced discomfort may improve the likelihood of future mammographic screening and early detection of breast cancer.

Relationships between repeated sprint testing, speed, and endurance.

Repeated sprint testing is gaining popularity in team sports, but the methods of data analysis and relationships to speed and endurance qualities are not well described. We compared three different methods for analyzing repeated sprint test results, and we quantified relationships between repeated sprints, short sprints, and endurance test scores. Well-trained male junior Australian Football players (n = 60, age 18.1 +/- 0.4 years, height 1.88 +/- 0.07 m, mass 82.0 +/- 8.1 kg; mean +/- SD) completed a 6 x 30-m repeated sprint running test on a 20-second cycle, a 20-m sprint test (short sprint), and the 20-m multistage shuttle run for endurance. Repeated sprint results were evaluated in three ways: total time for all six sprints (TOTAL), percent change from predicted times (PRED) from the fastest 30-m sprint time, and percent change from first to last sprint (CHANGE). We observed a very large decrement (CHANGE 6.3 +/- 0.7%, mean +/- 90% confidence limits) in 30-m performance from the first to last sprint (4.16 +/- 0.10 to 4.42 +/- 0.11 seconds, mean +/- SD). Results from TOTAL were highly correlated with 20-m sprint and 20-m multistage shuttle run tests. Performance decrements calculated by PRED were highly correlated with TOTAL (r = 0.91), but neither method was directly comparable with CHANGE (r = -0.23 and r = 0.12 respectively). TOTAL was moderately correlated with fastest 20-m sprint time (r = 0.66) but not the 20-m multistage shuttle run (r = -0.20). Evaluation of repeated sprint testing is sensitive to the method of data analysis employed. The total sprint time and indices of the relative decrement in performance are not directly interchangeable. Repeated sprint ability seems more related to short sprint qualities than endurance fitness.

3×3 Basketball: Performance Characteristics and Changes During Elite Tournament Competition.

PURPOSE: To determine the changes in game performance during tournament play of elite 3×3 basketball. METHODS: A total of 361 men and 208 women competing in selected international tournaments had game demands assessed by wearable technology (global positioning system, inertial sensor, and heart rate) along with postgame blood lactate and perceived responses. Differences in the means for selected variables between games were compared using magnitude-based inferences and reported with effect size and associated confidence limits (CL), along with the percentage difference (ES; ±90% CL, %difference) of log-transformed data. RESULTS: No clear differences were seen over a tournament period in PlayerLoad™ or PlayerLoad·minute-1. Tournament competition elicits variable changes between games for all inertial measures. Average peak heart rate was 198 (10) and 198 (9) beats·min-1, and average game heart rate was 164 (12) and 165 (18) beats·min-1 for men and women, respectively, with no change between games. Average game lactate was 6.3 (2.4) and 6.1 (2.2) mmol·L-1 for men and women, respectively. Average game ratings of perceived exertion were 5.7 (2.1) and 5.4 (2.0) AU for men and women, respectively. Although lactate and ratings of perceived exertion were variable between games, there was no difference over a tournament. CONCLUSIONS: The physical and physiological demands of elite 3×3 games over the duration of a tournament are similar regardless of pool or championship rounds. This may imply that maintaining technical and strategic aspects leads to success rather than minimizing fatigue through superior physical preparation. However, the physiological responses are high; caution is warranted in being underprepared for these demands in tournament play.

Three-by-Three Basketball: Inertial Movement and Physiological Demands During Elite Games.

PURPOSE: To determine the demands of elite male and female 3 × 3 basketball games and compare these between various competition levels. METHODS: A total of 361 males and 208 females competing in the Under-18 World, Senior European, and World Championships and selected professional tournaments had game demands assessed by wearable technology (global positioning system, inertial measurement, heart rate) along with postgame blood lactate and perceived responses. Differences in the means were compared using magnitude-based inferences and reported with effect size and 90% confidence limits, along with the percentage difference (effect size; ±90% confidence limits, %) of log-transformed data. RESULTS: PlayerLoad™ and PlayerLoad·min-1 during play was 127.5 (31.1) and 6.7 (1.5) for males and 128.5 (32.0) and 6.5 (1.4) for females, respectively, with small differences between junior, senior, and professional levels. There were small differences in accelerations >3.5 m·s-1 between competition levels up to 0.31; ±0.20, 6.9% for males and 0.29; ±0.19, 10.8% for females and for decelerations >3.5 m·s-1, 0.29; ±0.19, 15.6% for males and 0.26; ±0.19, 5.4% for females, with European Championships generally greater than other levels. Average game heart rate was 165 (18) and 164 (12) beats·min-1 for males and females, with no difference between levels. Average rating of perceived exertion was 5.7 (2.1) and 5.4 (2.0) for males and females. CONCLUSIONS: 3 × 3 basketball games require high-speed inertial movements within limited distance, creating a relatively high physiological response. Practitioners working with 3 × 3 players should endeavor to focus on the attributes that will improve these player characteristics for greater success.

Effect of different protocols of caffeine intake on metabolism and endurance performance.

Competitive athletes completed two studies of 2-h steady-state (SS) cycling at 70% peak O(2) uptake followed by 7 kJ/kg time trial (TT) with carbohydrate (CHO) intake before (2 g/kg) and during (6% CHO drink) exercise. In Study A, 12 subjects received either 6 mg/kg caffeine 1 h preexercise (Precaf), 6 x 1 mg/kg caffeine every 20 min throughout SS (Durcaf), 2 x 5 ml/kg Coca-Cola between 100 and 120 min SS and during TT (Coke), or placebo. Improvements in TT were as follows: Precaf, 3.4% (0.2-6.5%, 95% confidence interval); Durcaf, 3.1% (-0.1-6.5%); and Coke, 3.1% (-0.2-6.2%). In Study B, eight subjects received 3 x 5 ml/kg of different cola drinks during the last 40 min of SS and TT: decaffeinated, 6% CHO (control); caffeinated, 6% CHO; decaffeinated, 11% CHO; and caffeinated, 11% CHO (Coke). Coke enhanced TT by 3.3% (0.8-5.9%), with all trials showing 2.2% TT enhancement (0.5-3.8%; P < 0.05) due to caffeine. Overall, 1) 6 mg/kg caffeine enhanced TT performance independent of timing of intake and 2) replacing sports drink with Coca-Cola during the latter stages of exercise was equally effective in enhancing endurance performance, primarily due to low intake of caffeine (approximately 1.5 mg/kg).

Developing a protocol for obtaining blood cultures from central venous catheters and peripheral sites.

Blood cultures frequently are obtained from patients with cancer who are suspected to have infection. A review of the literature revealed that consistent clinical guidelines or standards for obtaining blood cultures from patients with cancer do not exist. The published literature varies greatly with respect to site selection (peripheral or central), frequency, and timing. In addition, a survey at the researchers' institution revealed that blood culture orders were written and interpreted in various ways. After a multidisciplinary discussion, a review of the literature, and receiving expert advice, an institutional protocol for obtaining blood cultures from patients with cancer was developed. The protocol specifies between peripheral and central line sampling and establishes timing, frequency, and other guidelines so nurses can perform consistent and evidence-based blood culture sampling. Use of the protocol has improved patient care and helped standardize the practice of obtaining blood cultures.

The effects of game and training loads on perceptual responses of muscle soreness in Australian football.

Australian Football is an intense team sport played over ~120 min on a weekly basis. To determine the effects of game and training load on muscle soreness and the time frame of soreness dissipation, 64 elite Australian Football players (age 23.8 ± 1.8 y, height 183.9 ± 3.8 cm, weight 83.2 ± 5.0 kg; mean ± SD) recorded perceptions of muscle soreness, game intensity, and training intensity on scales of 1-10 on most mornings for up to 3 competition seasons. Playing and training times were also recorded in minutes. Data were analyzed with a mixed linear model, and magnitudes of effects on soreness were evaluated by standardization. All effects had acceptably low uncertainty. Game and training-session loads were 790 ± 182 and 229 ± 98 intensity-minutes (mean ± SD), respectively. General muscle soreness was 4.6 ± 1.1 units on d 1 postgame and fell to 1.9 ± 1.0 by d 6. There was a small increase in general muscle soreness (0.22 ± 0.07-0.50 ± 0.13 units) in the 3 d after high-load games relative to low-load games. Other soreness responses showed similar timelines and magnitudes of change. Training sessions made only small contributions to soreness over the 3 d after each session. Practitioners should be aware of these responses when planning weekly training and recovery programs, as it appears that game-related soreness dissipates after 3 d regardless of game load and increased training loads in the following week produce only small increases in soreness.

Toxicity of topical lidocaine applied to the breasts to reduce discomfort during screening mammography.

BACKGROUND: We measured the effect of 30 milliliters (mL) of 4% lidocaine gel on the breasts and chest wall of healthy women covered for 1 h on plasma concentrations of lidocaine and its principal metabolite, monoethylglycinexylidide (MEGX), electrocardiogram (EKG) results, and adverse events. MATERIALS AND METHODS: This institutional review board-approved, prospective, open-label study complied with the Health Insurance Portability and Accountability Act (HIPAA). The study evaluated 10 healthy women aged 42-75 years with 30 mL of 4% lidocaine gel on the skin of the breasts and chest wall covered for 1 h. Cardiac and neurological assessments were performed and blood was drawn for lidocaine and MEGX levels at baseline and 1/2, 1, 2, 3, 4, 6, and 8 h after application. EKGs were performed before application and at 3 h. Subjects provided informed written consent. Primary and secondary outcomes were plasma concentrations of lidocaine and MEGX and frequency of adverse events, respectively. Statistical analysis included paired t-tests for EKGs and repeated measures regression for vital signs. RESULTS: No lidocaine was detected in the blood of 9 of 10 subjects. One subject had low plasma concentrations of lidocaine just above the level of detection the first 4 h after application only. No MEGX was detected. Mean decrease in heart rate was likely multifactorial. CONCLUSION: Thirty mL of 4% lidocaine gel on the breasts and chest wall covered for 1 h in healthy women resulted in plasma concentrations of lidocaine and MEGX well below therapeutic or toxic levels and no clinically significant adverse events.

The physical and physiological demands of basketball training and competition.

PURPOSE: To characterize the physical and physiological responses during different basketball practice drills and games. METHODS: Male basketball players (n=11; 19.1+/-2.1 y, 1.91+/-0.09 m, 87.9+/-15.1 kg; mean+/-SD) completed offensive and defensive practice drills, half court 5on5 scrimmage play, and competitive games. Heart rate, VO2, and triaxial accelerometer data (physical demand) were normalized for individual participation time. Data were log-transformed and differences between drills and games standardized for interpretation of magnitudes and reported with the effect size (ES) statistic. RESULTS: There was no substantial difference in the physical or physiological variables between offensive and defensive drills; physical load (9.5%; 90% confidence limits+/-45); mean heart rate (-2.4%; +/-4.2); peak heart rate (-0.9%; +/-3.4); and VO2 (-5.7%; +/-9.1). Physical load was moderately greater in game play compared with a 5on5 scrimmage (85.2%; +/-40.5); with a higher mean heart rate (12.4%; +/-5.4). The oxygen demand for live play was substantially larger than 5on5 (30.6%; +/-15.6). CONCLUSIONS: Defensive and offensive drills during basketball practice have similar physiological responses and physical demand. Live play is substantially more demanding than a 5on5 scrimmage in both physical and physiological attributes. Accelerometers and predicted oxygen cost from heart rate monitoring systems are useful for differentiating the practice and competition demands of basketball.

Quantifying movement demands of AFL football using GPS tracking.

Global positioning system (GPS) monitoring of movement patterns is widespread in elite football including the Australian Football League (AFL). However documented analysis of this activity is lacking. We quantified the movement patterns of AFL football and differences between nomadic (midfield), forward and defender playing positions, and determined whether the physical demands have increased over a four season period. Selected premiership games were monitored during the 2005 (n=80 game files), 2006 (n=244), 2007 (n=632) and 2008 (n=793) AFL seasons. Players were fitted with a shoulder harness containing a GPS unit. GPS data were downloaded after games and the following measures extracted: total distance (km), time in various speed zones, maximum speed, number of surges, accelerations, longest continuous efforts and a derived exertion index representing playing intensity. In 2008 nomadic players covered per game 3.4% more total distance (km), had 4.8% less playing time (min), a 17% higher exertion index (per min), and 23% more time running >18kmh(-1) than forwards and defenders (all p<0.05). Physical demands were substantially higher in the 2008 season compared with 2005: an 8.4% increase in mean speed, a 14% increase in intensity (exertion index) and a 9.0% decrease in playing time (all p<0.05). Nomadic players in AFL work substantially harder than forwards and defenders in covering more ground and at higher running intensities. Increases in the physical demands of AFL football were evident between 2005 and 2008. The increasing speed of the game has implications for game authorities, players and coaching staff.

Seasonal progression and variability of repeat-effort line-drill performance in elite junior basketball players.

To determine gender differences, positional differences, and patterns of change in the performance of the basketball line-drill test, 93 male (mean age 16.8 years, s = 1.1) and 95 female (mean age 16.5 years, s = 1.0) basketball players undertook 516 line-drill tests over a 5-year period. Log-transformed performance times were analysed using a mixed model that included quadratic within-participant fixed effects for time in the season and time in the programme. Changes and differences were standardized for interpretation of magnitudes. Mean performance times were 28.0 s (s = 1.3) for males and 30.4 s (s = 1.3) for females. The mean pattern of change in performance within a season differed substantially between the sexes and playing positions: male guards and female centres showed moderate to very large improvements mid-season of 1.1% and 3.5% respectively (90% confidence limits +/-2.1% and +/-3.0%), while female guards and male forwards showed large to very large decrements of -1.6% (+/-2.6%) and -2.4% (+/-2.0%). Over 3 years, males improved performance across all three playing positions by 1.4% (+/-1.3%) and females by 2.9% (+/-1.4%). Males improved performance by 0.2% (+/-0.5%) per year, whereas the performance of females deteriorated by 0.6% (+/-0.4%) per year. The differing patterns of performance change presumably reflect variations in training and competition loads, with short-term fluctuations in performance being managed to promote longer-term improvements.

The effect of recovery strategies on physical performance and cumulative fatigue in competitive basketball.

To evaluate the effectiveness of recovery strategies on physical performance during a 3-day tournament style basketball competition, 29 male players (mean age 19.1 years, s= 2.1; height 1.84 m, s= 0.34; body mass 88.5 kg, s= 14.7) were assigned to one of three treatment groups: carbohydrate+stretching (7.7 g kg(-1) day(-1), s= 1.7; 'n = 9), cold water immersion (11 degrees C, 5 x 1; n = 10) or full leg compression garments (18 mmHg, approximately 18 h; n = 10). Effects of the recovery strategies on pre-post tournament performance tests were expressed as the mean change (% +/- standard deviation of the change score). Changes and differences were standardized for accumulated game time, assessed against the smallest worthwhile change for each test, and reported qualitatively. Accumulated fatigue was evident over the tournament with small to moderate impairments in performance tests. Sprint and agility performance decreased by 0.7% (s = 1.3) and 2.0% (s = 1.9) respectively. Vertical jump decreased substantially after the first day for all treatments, and remained suppressed post-tournament. Cold water immersion was substantially better in maintaining 20-m acceleration with only a 0.5% (s = 1.4) reduction in 20-m time after 3 days compared with a 3.2% (s = 1.6) reduction for compression. Cold water immersion (-1.4%, s = 1.7) and compression (-1.5%, s = 1.7) showed similar substantial benefits in maintaining line-drill performance over the tournament, whereas carbohydrate+stretching elicited a 0.4% (s =1.8) reduction. Sit-and-reach flexibility decreased for all groups, although cold water immersion resulted in the smallest reduction in flexibility. Basketball tournament play elicited small to moderate impairments in physical test performance. In conclusion, cold water immersion appears to promote better restoration of physical performance measures than carbohydrate + stretching routines and compression garments.