Different fever definitions and the rate of fever and neutropenia diagnosed in children with cancer: a retrospective two-center cohort study

Background. The definition of fever, and thus fever and neutropenia (FN), varies between different pediatric oncology centers. Higher temperature limit should reduce FN rates, but may increase rates of FN with complications by delaying therapy. This study determined if different fever definitions are associated with different FN rates. Procedure. Two pediatric oncology centers had used three fever definitions in 2004–2011: ear temperature >=38.5°C persisting >=2 hours (low definition); axillary temperature >=38.5°C >=2 hours or >=39.0°C once (middle); and ear temperature >=39.0°C once (high). Clinical information was retrospectively extracted from charts. FN rates were compared using mixed Poisson regression. Results. In 521 pediatric patients with cancer, 783 FN were recorded during 6,009 months cumulative chemotherapy exposure time (501 years; rate, 0.13/month [95% CI, 0.12–0.14]), 124 of them with bacteremia (16%; 0.021/month [0.017–0.025]). In univariate analysis, the high versus low fever definition was associated with a lower FN rate (0.10/month [0.08–0.11] vs. 0.15/month [0.13–0.16]; rate ratio, 0.66 [0.45–0.97]; P ¼ 0.036), the middle definition was intermediate (0.13/month [0.11–0.15]). This difference was not confirmed in multivariate analysis (rate ratio, 0.94 [0.67–1.33]; P ¼ 0.74). The high versus low definition was not associated with an increased rate of FN with bacteremia (multivariate rate ratio, 1.39 [0.53–3.62]; P ¼ 0.50). Conclusion. A higher fever definition was not associated with a lower FN rate, nor with an increased rate of FN with bacteremia. These may be false negative findings due to methodological limitations. These questions, with their potential impact on health-related quality of life, and on costs, need to be assessed in prospective studies.

Isometric rate of force development, maximum voluntary contraction, and balance in women with and without joint hypermobility

OBJECTIVE: To determine differences between hypermobile subjects and controls in terms of maximum strength, rate of force development, and balance. METHODS: We recruited 13 subjects with hypermobility and 18 controls. Rate of force development and maximal voluntary contraction (MVC) during single leg knee extension of the right knee were measured isometrically for each subject. Balance was tested twice on a force plate with 15-second single-leg stands on the right leg. Rate of force development (N/second) and MVC (N) were extracted from the force-time curve as maximal rate of force development (= limit Deltaforce/Deltatime) and the absolute maximal value, respectively. RESULTS: The hypermobile subjects showed a significantly higher value for rate of force development (15.2% higher; P = 0.038, P = 0.453, epsilon = 0.693) and rate of force development related to body weight (16.4% higher; P = 0.018, P = 0.601, epsilon = 0.834) than the controls. The groups did not differ significantly in MVC (P = 0.767, P = 0.136, epsilon = 0.065), and MVC related to body weight varied randomly between the groups (P = 0.921, P = 0.050, epsilon = 0.000). In balance testing, the mediolateral sway of the hypermobile subjects showed significantly higher values (11.6% higher; P = 0.034, P = 0.050, epsilon = 0.000) than that of controls, but there was no significant difference (4.9% difference; P = 0.953, P = 0.050, epsilon = 0.000) in anteroposterior sway between the 2 groups. CONCLUSION: Hypermobile women without acute symptoms or limitations in activities of daily life have a higher rate of force development in the knee extensors and a higher mediolateral sway than controls with normal joint mobility.

Seasonal variation of VO 2 max and the VO2-work rate relationship in elite Alpine skiers

PURPOSE: Alpine ski performance relates closely to both anaerobic and aerobic capacities. During their competitive season, skiers greatly reduce endurance and weight training, and on-snow training becomes predominant. To typify this shift, we compared exhaustive ramp cycling and squat (SJ) and countermovement jumping (CMJ) performance in elite males before and after their competitive season. RESULTS: In postseason compared with preseason: 1) maximal oxygen uptake (VO 2 max) normalized to bodyweight was higher (55.2 +/- 5.2 vs 52.7 +/- 3.6 mL x kg(-1) x min(-1), P < 0.01), but corresponding work rate (W) was unchanged; 2) at ventilatory thresholds (VT), absolute and relative work rates were similar but heart rates were lower; 3) VO2/W slope was greater (9.59 +/- 0.6 vs 9.19 +/- 0.4 mL O2 x min(-1) x W(-1), P = 0.02), with similar flattening (P < 0.01) above V T1 at both time points; and 4) jump height was greater in SJ (47.4 +/- 4.4 vs 44.7 +/- 4.3 cm, P < 0.01) and CMJ (52.7 +/- 4.6 vs 50.4 +/- 5.0 cm, P < 0.01). DISCUSSION: We believe that aerobic capacity and leg power were constrained in preseason and that improvements primarily reflected an in-season recovery from a fatigued state, which was caused by incongruous preseason training. Residual adaptations to high-altitude exposure in preseason could have also affected the results. Nonetheless, modern alpine skiing seemingly provides an ample cardiovascular training stimulus for skiers to maintain their aerobic capacities during the racing season. CONCLUSIONS: We conclude that aerobic fitness and leg explosiveness can be maintained in-season but may be compromised by heavy or excessive preseason training. In addition, ramp test V O2/W slope analysis could be useful for monitoring both positive and negative responses to training.

Antinociceptive effects of three escalating dexmedetomidine and lignocaine constant rate infusions in conscious horses.

Dexmedetomidine and lignocaine IV are used clinically to provide analgesia in horses. The aims of this study were to investigate the antinociceptive effects, plasma concentrations and sedative effects of 2, 4 and 6 µg/kg/h dexmedetomidine IV, with a bolus of 0.96 µg/kg preceding each continuous rate infusion (CRI), and 20, 40 and 60 µg/kg/min lignocaine IV, with a bolus of 550 µg/kg preceding each CRI, in 10 Swiss Warmblood horses. Electrically elicited nociceptive withdrawal reflexes were evaluated by deltoid muscle electromyography. Nociceptive threshold and tolerance were determined by electromyography and behaviour following single and repeated stimulation. Plasma concentrations of drugs were determined by liquid chromatography and mass spectrometry. Sedation was scored on a visual analogue scale. Dexmedetomidine increased nociceptive threshold to single and repeated stimulation for all CRIs, except at 2 µg/kg/h, where no increase in single stimulation nociceptive threshold was observed. Dexmedetomidine increased nociceptive tolerance to single and repeated stimulation at all CRIs. There was large individual variability in dexmedetomidine plasma concentrations and levels of sedation; the median plasma concentration providing antinociceptive effects to all recorded parameters was 0.15 ng/mL, with a range from <0.02 ng/mL (below the lower limit of quantification) to 0.25 ng/mL. Lignocaine increased nociceptive threshold and tolerance to single and repeated stimulation at CRIs of 40 and 60 µg/kg/min, corresponding to plasma lignocaine concentrations >600 ng/mL. Only nociceptive tolerance to repeated stimulation increased at 20 µg/kg/min lignocaine. Lignocaine at 40 µg/kg/min and dexmedetomidine at 4 µg/kg/h were the lowest CRIs resulting in consistent antinociception. Lignocaine did not induce significant sedation.

36Cl production rate from K-spallation in the European Alps (Chironico landslide, Switzerland)

The abundant production of in situ cosmogenic 36Cl from potassium renders 36Cl measurements in K-rich rocks or minerals, such as K-feldspars, potentially useful for precisely dating rock surfaces, either in single-nuclide or in multi-nuclide studies, for example combined with 10Be measurements in quartz. However, significant discrepancies in experimentally calibrated 36Cl production rates from spallation of potassium (36PK-sp), referenced to sea-level/high-latitude (SLHL), limit the accuracy of 36Cl dating from K-rich lithologies. We present a new 36Cl calibration using K-feldspars, in which K-spallation is the most dominant 36Cl production pathway (>92% of total 36Cl), thus minimizing uncertainties from the complex multi-pathway 36Cl production systematics. The samples are derived from boulders of an ∼13.4 ka-old landslide in the Swiss Alps (∼820 m, 46.43°N, 8.85°E). We obtain a local 36PK-sp of 306 ± 16 atoms 36Cl (g K)−1 a−1 and an SLHL 36PK-sp of 145.5 ± 7.7 atoms 36Cl (g K)−1 a−1, when scaled with a standard scaling protocol (‘Lm’). Applying this SLHL 36PK-sp to determine 36Cl exposure ages of K-feldspars from 10Be-dated moraine boulders yields excellent agreement, confirming the validity of the new SLHL 36PK-sp for surface exposure studies, involving 36Cl in K-feldspars, in the Alps.

The influence of different fever definitions on the rate of fever in neutropenia diagnosed in children with cancer

BACKGROUND The temperature limit defining fever (TLDF) is based on scarce evidence. This study aimed to determine the rate of fever in neutropenia (FN) episodes additionally diagnosed by lower versus standard TLDF. METHODS In a single center using a high TLDF (39.0°C tympanic temperature, LimitStandard), pediatric patients treated with chemotherapy for cancer were observed prospectively. Results of all temperature measurements and CBCs were recorded. The application of lower TLDFs (LimitLow; range, 37.5°C to 38.9°C) versus LimitStandard was simulated in silicon, resulting in three types of FN: simultaneous FN, diagnosed at both limits within 1 hour; earlier FN, diagnosed >1hour earlier at LimitLow; and additional FN, not diagnosed at LimitStandard. RESULTS In 39 patients, 8896 temperature measurements and 1873 CBCs were recorded during 289 months of chemotherapy. Virtually applying LimitStandard resulted in 34 FN diagnoses. The predefined relevantly (≥15%) increased FN rate was reached at LimitLow 38.4°C, with total 44 FN, 23 simultaneous, 11 earlier, and 10 additional (Poisson rate ratioAdditional/Standard, 0.29; 95% lower confidence bound, 0.16). Virtually applying 37.5°C as LimitLow led to earlier FN diagnosis (median, 4.5 hours; 95% CI, 1.0 to 20.8), and to 53 additional FN diagnosed. In 51 (96%) of them, spontaneous defervescence without specific therapy was observed in reality. CONCLUSION Lower TLDFs led to many additional FN diagnoses, implying overtreatment because spontaneous defervescence was observed in the vast majority. Lower TLDFs led as well to relevantly earlier diagnosis in a minority of FN episodes. The question if the high TLDF is not only efficacious but as well safe remains open.

Limited Correlation between Expansin Gene Expression and Elongation Growth Rate

The aim of this work was to study the role of the cell wall protein expansin in elongation growth. Expansins increase cell wall extensibility in vitro and are thought to be involved in cell elongation. Here, we studied the regulation of two tomato (Lycopersicon esculentum cv Moneymaker) expansin genes,LeExp2 and LeExp18, in rapidly expanding tissues. LeExp2 was strongly expressed in the elongation zone of hypocotyls and in the faster growing stem part during gravitropic stimulation. LeExp18 expression did not correlate with elongation growth. Exogenous application of hormones showed a substantial auxin-stimulation of LeExp2 mRNA in etiolated hypocotyls and a weaker auxin-stimulation ofLeExp18 mRNA in stem tissue. Analysis of transcript accumulation revealed higher levels of LeExp2 andLeExp18 in light-treated, slow-growing tissue than in dark-treated, rapidly elongating tissue. Expansin protein levels and cell wall extension activities were similar in light- and dark-grown hypocotyl extracts. The results show a strong correlation between expansin gene expression and growth rate, but this correlation is not absolute. We conclude that elongation growth is likely to be controlled by expansin acting in concert with other factors that may limit growth under some physiological conditions.