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Background Adult meta-analyses have verified that adjunct use of alpha-2 adrenoceptor agonists (A2 AA) together with local anesthetics ( LA) will prolong the duration of peripheral nerve blocks. The standard use of A2 AAs for peripheral nerve blockade has recently been recommended also in children, but the evidence base in support of this suggestion has to date been equivocal. The purpose of this meta-analysis was to produce evidence-based data regarding the effect in children. Methods Following a thorough literature search, five randomized controlled trials were included in a meta-analysis. Raw data from all studies were gathered and aggregated into patients randomized to receive plain LA (Group PLA) or LA mixed with either adjunct clonidine or dexmedetomidine (Group ADJ). The main outcome parameter was block duration (time to first administration of supplemental analgesic based on predetermined pain scores) analyzed by survival statistics. The total number of supplemental analgesic doses during the first 24 postoperative hours and serious side effects were included as secondary outcomes. Results Pooling of the study data generated 141 patients in Group PLA and 142 patients in Group ADJ (overall n = 283; age: 0.8-13 years; weight 8-47 kg). Block duration was significantly prolonged (9.75 h vs 3.75 h) compared to the use of plain LA. Survival statistics verified a beneficial effect of using adjunct A2 AAs [the log rank (Mantel-Cox) test ( P = 0.0078), Gehan-Breslow-Wilcoxon test ( P = 0.0027), and hazard ratio (1.653; 95% CI: 1.142 to 2.395)]. The number of patients that needed ≥2 doses of supplemental analgesics was higher in Group PLA ( n = 19) compared to Group ADJ ( n = 6) ( P = 0.0088). No serious side effects were reported. Conclusion This meta-analysis provides evidence-based support for the use of adjunct alpha-2 adrenoceptor agonists when performing peripheral nerve blocks in children. [ABSTRACT FROM AUTHOR]

Background Administration of local anesthetics by a surgically placed wound catheter has recently been shown to reduce the need for postoperative morphine administration in extremely preterm infants undergoing ductus ligation. The primary aim of this randomized safety study was to define the plasma levels of levobupivacaine ( LB) following two different intermittent infusion regimens. Methods Eighteen preterm infants 23-27 gestational weeks, median birthweight 721 g scheduled for ductus ligation were included in the study. All patients were anesthetized according to a standardized protocol based on high-dose fentanyl (25-50 μg·kg−1). Before skin closure, a subcutaneous catheter was inserted into the wound. The patients were randomized to receive one of the two intermittent infusion regimens: Group BII: Initial bolus plus early start of the intermittent infusion or Group DII: No bolus plus delayed start (8 h) of the intermittent infusion. Blood samples for determination of LB plasma concentrations were obtained on six occasions during the 24-h postoperative observation period, as well as hourly postoperative pain assessments using the Echelle Douleur Inconfort Noveau ( EDIN) pain scale. Results Plasma concentrations of LB ranged from 0.094 to 1.682 μg·ml−1 and 0 to 0.549 μg·ml−1 in group BII and DII, respectively. Both regimens were associated with low postoperative EDIN pain scores (24 h median of 0 and 1 in group BII and DII, respectively). No signs of systemic local anesthetic toxicity were noted. Conclusions The two studied intermittent infusion regimens were associated with plasma levels below potentially toxic levels and were both associated with adequate postoperative pain scores. [ABSTRACT FROM AUTHOR]

Background Bortezomib is a proteasome inhibitor currently studied in clinical trials of childhood cancers. So far, no side effects on bone growth have been reported in treated children. However, bortezomib was recently found to induce apoptosis in growth plate chondrocytes and impair linear bone growth in treated mice. We hypothesize that [Gly14] humanin (HNG), a 24-amino acid synthetic antiapoptotic peptide, can prevent bortezomib-induced bone growth impairment. Methods Mice with human neuroblastoma or medulloblastoma tumor xenografts (9-13 animals/group) received one 2-week cycle (2 injections/week) of bortezomib (0.8 mg/kg or 1.0 mg/kg), or HNG (1 µg/mouse), or the combination of HNG/bortezomib, or vehicle. Cultures of human growth plate cartilage, chondrogenic- and cancer cell lines, and immunohistochemistry for detection of proapoptotic proteins were also used. Statistical significance was evaluated by two-sided Mann-Whitney U test or by parametric or nonparametric analysis of variance. Results Bortezomib efficiently blocked the proteasome and induced pronounced impairment of linear bone growth from day 0 to day 13 (0.09 mm/day, 95% confidence interval [Cl] = 0.07 to 0.11 mm/day; vs 0.19 mm/day, 95% Cl = 0.15 to 0.23mm/day in vehicle; P< .001), an effect significantly prevented by the addition of HNG (0.15ram growth/day, 95% CI = 0.14 to 0.16mm/day; P< .001 vs bortezomib only; P= 0.03 vs vehicle). Bortezomib was highly toxic when added to cultures of human growth plate cartilage, with markedly increased apoptosis compared with control (P < .001). However, when combining with HNG, bortezomib-induced apoptosis was entirely prevented, as was Bax and PARP activation. Bortezomib delayed tumor growth, and HNG did not interfere with the anticancer effect when studied in human tumor xenografts or cell lines. Conclusions HNG prevents bortezomib-induced bone growth impairment without interfering with bortezomib's desired anti- cancer effects. [ABSTRACT FROM AUTHOR]

Background: The α2 agonist clonidine has become a popular drug for premedication in children. Effects and pharmacokinetics after oral, rectal, and intravenous administration are well known. The aim of this study was to investigate the absorption pharmacokinetics of clonidine nasal drops in children. Methods: Thirteen ASA I pediatric patients received after induction of anesthesia 4 mcg·kg−1 of clonidine by the nasal route. Blood samples were taken during a 12-h period and plasma levels of clonidine were analyzed by liquid chromatography–mass spectrometry. Data were calculated by a computer-aided curve-fitting program. Results: Plasma pharmacokinetics following administration of clonidine nasal drops showed a considerable interindividual variability and absorption was delayed and limited. A total of 95% confidence intervals for maximum plasma concentration and time to achieve maximum plasma concentration were 0.4–0.6 ng·ml−1 and 1.4–3.0 h, respectively. Conclusions: Clonidine nasal drops are erratically absorbed from the nasal mucosa and, thus, this mode of drug administration is not recommended for premedication purposes. [ABSTRACT FROM AUTHOR]

Depending on stage and risk factors, up to 30% of patients with advanced Hodgkin lymphoma (HL) progress or relapse. Patients with pleural effusions have a particularly poor prognosis and this stage of HL is regularly resistant to chemotherapy. All currently available HL cell lines are derived from late stage HL patients. In the present study we measured the sensitivity of these HL lines against the 26 most frequently used cytostatic drugs. We used a novel fluorescent short-term survival assay where the cell was incubated with the drugs for 4 days. The precise number of differentially stained live and dead cells was determined using a custom-built automated laser confocal fluorescent microscope. We found that HL cells, independently of their origin, showed very similar sensitivity patterns for several of the drugs. All HL cell lines were highly sensitive to dactinomycin, paclitaxel and etoposide. Our data suggest that the inclusion of dactinomycin and paclitaxel into chemotherapy protocols against late stage Hodgkin lymphoma with pleural effusion may be justified. [ABSTRACT FROM AUTHOR]

Objective: To determine the workplace concentrations of NO and NO(2) in and around a paediatric incubator during inhaled NO (iNO) treatment and during an accidental emptying of NO cylinders into room air.Design: We simulated iNO-nasal CPAP treatment in order to assess the impact on the occupational environment. Furthermore, two full NO cylinders for therapy, 1,000 ppm, 20 litres, 150 bar and 400 ppm, 10 litres, 150 bar, were emptied as rapidly as possible into an intensive care unit (ICU) room.Setting: University hospital ICU.Measurements and Results: To correctly gauge the contribution from iNO-CPAP we constructed a system measuring breathing zone and room ventilation inlet-outlet values during a 10-ppm iNO treatment of a simulated infant. Maximal breathing zone values were 17.9 +/- 7.0 (mean +/- 95% CI) ppb for NO and 25.2 +/- 4.8 ppb for NO(2). If room inlet values were subtracted, the contributions to breathing zone values emanating from iNO-CPAP were 14.8 +/- 4.6 ppb for NO and 14.6 +/- 4.6 ppb for NO(2). At the ventilation outlet the maximal contributions were 4.2 +/- 2.9 ppb NO and 9.6 +/- 4.3 ppb NO(2). During rapid total release of a gas cylinder in the ICU room, simulating an accident, we found transient NO levels comparable to the high therapeutic dosing range, but only low NO(2) levels.Conclusions: Neither 8-h time-weighted average (TWA) nor 15 min short-term exposure limits (STEL) were exceeded during normal operation or during a simulated accident. The contribution of nitrogen oxides from treatment to workplace air were minor compared to those from ambient air. [ABSTRACT FROM AUTHOR]

Background: Temozolomide (TMZ) is an alkylating agent with a broad spectrum of antitumor activity, including brain tumors in children. The oral use of TMZ is hampered by the lack of a suitable galenic formulation, since the capsules of TMZ (TemodalTM) are large and difficult to swallow. A powder for preparation of a TMZ solution for intravenous administration (2.5 mg/mL) has recently been approved. A possibility to use this formulation for oral administration would facilitate TMZ administration. Aim: The aim of the present study was to investigate the stability of TMZ in solutions prepared from the commercially available powder for intravenous infusion. Materials and Methods: Solutions were prepared from the intravenous formulation by dissolving the powder in water. The degradation of TMZ was studied photometrically at 330 nm in two solutions, 2.5 mg/mL at room temperature (RT; 22°C) and 1.25 mg/mL at 5°C, prepared from the intravenous formulation. Results: More than 90% of TMZ remained intact after storage for 9 days at RT (2.5 mg/mL) and 13 weeks at 5°C (1.25 mg/mL). Conclusions: The high stability of a TMZ solution prepared from the powder for infusion formulation makes it suitable for oral administration. Oral use of a TMZ solution facilitates administration of the drug to patients with difficulties to swallow capsules, and enables a more flexible and precise dosing. [ABSTRACT FROM AUTHOR]

Objective: The use of extracorporeal membrane oxygenation in adults with respiratory failure and sepsis is steadily increasing, but the knowledge on long-term survival in this group is scarce. The aim of the present study was to investigate the 5-year survival rates and causes of late death in this group of patients.Design: Single-center retrospective cohort study.Setting: Karolinska University Hospital, Stockholm, Sweden.Patients: Adult patients treated with extracorporeal membrane oxygenation for respiratory failure and sepsis between the service being established for adults in 1995 and December 2013.Interventions: None.Measurements and Main Results: Survival status was attained from a national Causes of Death registry. Minimal patient background data, along with data on survival and causes of death were collected. Survival rates were calculated using the Kaplan-Meier method. Of 255 subjects, 64% survived to discharge. The median follow-up time in survivors was 4.4 years. There was a high mortality rate within the first months after discharge. In the group of patients who survived the first 90 days after treatment, the 5-year survival rate was 87% and was particularly beneficial in patients treated for infectious diseases (88-100%). Late deaths were seen in most diagnostic groups, but the Kaplan-Meier curves flattened out over time.Conclusions: Extracorporeal membrane oxygenation treatment in adult patients with respiratory failure and sepsis can be lifesaving in appropriately selected patients. For patients who survive the first months after extracorporeal membrane oxygenation treatment, long-term survival seems good, especially in patients treated for infections. [ABSTRACT FROM AUTHOR]