Safety Of Prophylactic Use Research Articles

Efficacy and safety of prophylactic use of benzhexol after risperidone treatment in MK-801-induced mouse model of schizophrenia

Efficacy and safety of prophylactic use of benzhexol after risperidone treatment in MK-801-induced mouse model of schizophrenia

Comparison of Efficacy and Safety of Prophylactic Use of Metoclopramide and Haloperidol on Morphine-induced Nausea and Vomiting in Cancer Patients: A Comparative, Randomised, Prospective Study

Objectives: Morphine is the cornerstone of pain management in a palliative care setting. Nausea with or without vomiting usually occurs when patients are initiated on morphine for the 1st time or when the dose is substantially increased. Materials and Methods: A total of 90 patients fulfilling the inclusion criteria were randomly allocated into two groups of 45 each. Group M received a tablet of metoclopramide 10 mg orally 3 times a day; Group H received a tablet of haloperidol (2.5 mg) orally at night. All the patients were provided NCI CTCAE V4.3 NAUSEA AND VOMITING SCALE and asked to mark their response from day 1 to day 7. At the follow-up visit on the 7th day, the form was collected, and data were analysed. Results: In Group M and Group H, the mean nausea score was between 1 and 2 and the difference was statistically insignificant. In Group M, the maximum vomiting score was 1.28 on day 5, while in Group H, the maximum score was 2 on day 5. The difference between the two groups was statistically significant. Conclusion: Metoclopramide and haloperidol are equally efficacious in preventing nausea, but metoclopramide was found to be more effective with lesser side effects than haloperidol for morphine-induced vomiting in cancer patients when used prophylactically.

Efficacy and safety of prophylactic use of benzhexol after risperidone treatment

To test the effect of prophylactic use of benzhexol in schizophrenia patients after risperidone treatment. Sixty-nine drug naïve schizophrenia patients were recruited. All patients were administered risperidone. Patients in the benzhexol group were given a benzhexol tablet of 2 mg bid daily. The controls received a placebo tablet of 2 mg bid daily. The primary outcome measured using the Extrapyramidal Symptoms Rating Scale (ESRS). The Positive and Negative Syndrome Scale (PANSS) and the Brief Psychiatric Rating Scale (BPRS) measured secondary outcome. There were significant time and group effects on the ESRS scores of the two groups. The post hoc analysis yielded significant differences at 1, 2, 4, and 8 weeks between the two groups. There was a significant time effect on the PANSS scores of the two groups. No significant group and interaction effects on the PANSS scores of the two groups. There was a significant time effect on the BPRS scores of the two groups. No serious adverse events were found in this study. Prophylactic use of benzhexol reduced extrapyramidal symptom in schizophrenia patients after risperidone treatment and did not affect the antipsychotic action of risperidone.

Efficacy and safety of prophylactic use of ketamine for prevention of postanesthetic shivering: a systematic review and meta analysis

BackgroundPostanesthetic shivering is a common complication of anesthesia, which accounts for much discomfort in postoperative patients and may increase postoperative complications in high-risk patients. Due to the lack of high-quality evidence, it is difficult to draw a conclusion about optimal anti-shivering medication. The main purpose of this meta-analysis was to analyze and evaluate the efficacy and safety of prophylactic use of ketamine for preventing postanesthetic shivering.MethodsWe searched the following databases: Medline, Embase, and the Cochrane Central Register of Controlled Trails for randomized controlled trials. The primary outcome observed was the difference of the incidence rate of postanesthetic shivering between ketamine group and placebo group. The secondary outcomes were the sedation score and incidence of the side effects caused by ketamine and any other drugs utilized in the studies.ResultsIn this meta-analysis, we analyzed a total of 16 trials including 1485 patients. Ketamine reduced the incidence rate of postanesthetic shivering compared to a placebo (odds ratio [OR]: 0.13, 95% confidence interval [CI]: 0.06 to 0.26, P<0.01). Regarding side effects, there was no evident variability of the incidence of nausea and vomiting. Usage of ketamine was associated with a lower rate of hypotension and bradycardia when compared to a placebo. Hallucinations were more frequently observed in patients who received higher doses of ketamine. No significant difference was found in the incidence of postanesthetic shivering with ketamine versus other pharmacological interventions.ConclusionsKetamine can prevent postanesthetic shivering without severe side effects. However, ketamine shows no advantage over other anti-shivering drugs.

The efficacy and safety of prophylactic use of levosimendan on patients undergoing coronary artery bypass graft: a systematic review and meta-analysis.

Prophylactic use of levosimendan in cardiac surgery remains controversial and no meta-analysis has been done exclusively about that in patients undergoing coronary artery bypass graft (CABG) surgery. We conducted this systematic review and meta-analysis of levosimendan in CABG using PubMed, Embase, Scopus, and Cochrane Library (till April 20, 2018). Two-hundred and forty manuscripts were identified and 21 randomized trials (1727 patients in total) investigating the effect of levosimendan on the patients undergoing CABG surgery were finally included in this analysis. We found that levosimendan was an effective, well-tolerated inotropic agent in CABG, which was associated with a significantly reduced mortality rate [odds ratio (OR) 0.43, 95% confidence interval (CI) (0.26, 0.71), p = 0.001, I2 = 0%] and postoperative atrial fibrillation [OR 0.50, 95% CI (0.26, 0.97), p = 0.04, I2 = 76%], but a higher incidence of hypotension [OR 2.26, 95% CI (1.05, 4.85), p = 0.04, I2 = 79%]. Subgroup analyses revealed that such a benefit was mainly observed in the isolated CABG, the preoperative administration, with-bolus and on-pump subgroups. More high-quality and well-designed prospective studies are needed to confirm or disprove our findings in future.

AB148. 43. Systematic review and meta-analysis of randomised controlled trials analysing the role of drains following infraperitoneal colorectal or coloanal anastomosis

Background: Anastomotic dehiscence leading to pelvic sepsis after infra-peritoneal anastomosis is a significant challenge in colorectal surgery. The prophylactic use of pelvic drains to reduce the incidence of and improve the early diagnosis of anastomotic leakage remains a common surgical practice despite any strong evidence relating to its efficacy and safety. This systematic review assessed the efficacy and safety of prophylactic use of pelvic drains in infra-peritoneal anastomosis.

The role of prophylactic use of pegylated recombinant human granulocyte colony-stimulating factor(PEG-rhG-CSF) in breast cancer receiving adjuvant chemotherapy

Objectives: To investigate the efficacy and safety of prophylactic use of pegylated recombinant human granulocyte colony-stimulating factor(PEG-rhG-CSF) in breast cancer receiving docetaxel as adjuvant chemotherapy. Methods: A total of 58 patients with breast cancer receiving adjuvant chemotherapy with docetaxel were included between January 2014 to October 2017. Prophylactic use of PEG-rhG-CSF was administered.Patients were further divided into two groups according to the frequency of PEG-rhG-CSF use: frequent use group (≥3 cycles) and non-frequent use group (<3 cycles). Results: There were significant differences in the incidence rates of grade 3/4 neutropenia between the prophylactic group and non-prophylactic group in cycle 1-3(P<0.05). Less febrile neutropenia (FN) was also noted in the prophylactic group compared with the non-prophylactic group in cycle 1 and cycle 3 (P<0.05). Grade 3/4 neutropenia and FN were less in the frequent use of group compared with the non-frequent use group(P<0.001). The most common side effects of PEG-rhG-CSF included fatigue (10.2%), bone joint pain(50.8%), and 2 patients (3.4%) refused further treatment because of bone joint pain. Conclusions: PEG-rhG-CSF should be prophylactically used for preventing neutropenia and febrile neutropenia in breast cancer patients receiving adjuvant chemotherapy with docetaxel regimen.

Prophylactic use of ergot alkaloids in the third stage of labour.

Previous research has shown that the prophylactic use of uterotonic agents in the third stage of labour reduces postpartum blood loss and moderate to severe postpartum haemorrhage (PPH). PPH is defined as a blood loss of 500 mL or more within 24 hours after birth. This is one of a series of systematic reviews assessing the effects of prophylactic use of uterotonic drugs; in this review prophylactic ergot alkaloids as a whole, and different regimens of administration of ergot alkaloids, are compared with no uterotonic agents. This is an update of a Cochrane Review which was first published in 2007 and last updated in 2011. To determine the effectiveness and safety of prophylactic use of ergot alkaloids in the third stage of labour by any route (intravenous (IV), intramuscular (IM), or oral) compared with no uterotonic agents, for the prevention of PPH. For this update, we searched the Cochrane Pregnancy and Childbirth Group's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (19 September 2017); we also searched reference lists of retrieved studies. We included all randomised controlled trials or cluster-randomised trials comparing prophylactic ergot alkaloids by any route (IV, IM, or oral) with no uterotonic agents in the third stage of labour among women giving birth vaginally. Two review authors independently assessed trials for inclusion, extracted data and checked them for accuracy; they also assessed the risk of bias in included studies. Two review authors assessed the quality of the evidence using the GRADE approach. There were eight included studies: three studies had a low risk of bias and five studies had high risk of bias. The studies compared ergot alkaloids with no uterotonic agents, with a total of 2031 women in the ergot alkaloids group and 1978 women in the placebo or no treatment group. Seven studies used the IV/IM route of administration and one study used the oral route.Ergot alkaloids (any route of administration) versus no uterotonic agentsUse of ergot alkaloids in the third stage of labour decreased mean blood loss (mean difference (MD) -80.52 mL, 95% confidence interval (CI) -96.39 to -64.65 mL; women = 2718; studies = 3; moderate-quality evidence); decreased PPH of at least 500 mL (average risk ratio (RR) 0.52, 95% CI 0.28 to 0.94; women = 3708; studies = 5; I2 = 83%; low-quality evidence); increased maternal haemoglobin concentration (g/dL) at 24 to 48 hours postpartum (MD 0.50 g/dL, 95% CI 0.38 to 0.62; women = 1429; studies = 1; moderate-quality evidence); and decreased the use of therapeutic uterotonics (average RR 0.37, 95% CI 0.15 to 0.90; women = 2698; studies = 3; I2 = 89%; low-quality evidence). There were no clear differences between groups in severe PPH of at least 1000 mL (average RR 0.32, 95% CI 0.04 to 2.59; women = 1718; studies = 2; I2 = 74%; very low-quality evidence). The risk of retained placenta or manual removal of the placenta, or both, were inconsistent with high heterogeneity. Ergot alkaloids increased the risk of elevated blood pressure (average RR 2.60, 95% CI 1.03 to 6.57: women = 2559; studies = 3; low-quality evidence) and pain after birth requiring analgesia (RR 2.53, 95% CI 1.34 to 4.78: women = 1429; studies = 1; moderate-quality evidence) but there were no differences between groups in vomiting, nausea, headache or eclamptic fit.Results for IV/IM ergot alkaloids versus no uterotonic agents were similar to those for the main comparison of ergot alkaloids administered by any route, since most of the studies (seven of eight) used the IV/IM route. Only one small study (289 women) compared oral ergometrine with placebo and it showed no benefit of ergometrine over placebo. No maternal adverse effects were reported.None of the studies reported on any of our prespecified neonatal outcomes AUTHORS' CONCLUSIONS: Prophylactic IM or IV injections of ergot alkaloids may be effective in reducing blood loss, reducing PPH (estimated blood loss of at least 500 mL), and increasing maternal haemoglobin. Ergot alkaloids may also decrease the use of therapeutic uterotonics, but adverse effects may include elevated blood pressure and pain after birth requiring analgesia. There were no differences between groups in terms of other adverse effects (vomiting, nausea, headache or eclamptic fit). There is a lack of evidence on the effects of ergot alkaloids on severe PPH, and retained or manual removal of placenta. There is also a lack of evidence on the oral route of administration of ergot alkaloids.

Garenoxacin Prophylaxis for Febrile Neutropenia after Chemotherapy in Hematological Malignancies

Background: Febrile neutropenia is one of the most serious adverse events in patients with hematological malignancies and chemotherapy. The routine use of fluoroquinolone prophylaxis in patients with hematological malignancies is controversial. Therefore, we prospectively evaluated the efficacy and safety of prophylactic use of garenoxacin for febrile neutropenia. Patients and Methods: Consecutive adult patients with hematological malignancies who were at risk for chemotherapy-induced neutropenia lasting more than seven days were eligible for present study. They received oral garenoxacin (400 mg daily) from the neutrophil count decreased to less than 1000/μl and continued until the neutropenia had resolved. The primary endpoint was incidence of febrile neutropenia, and the secondary endpoints were the type and incidence of adverse events. Results: We enrolled 46 consecutive patients (median age, 59 years). The underlying diseases comprised acute myeloid leukemia (n = 17), acute lymphoblastic leukemia (n = 3), malignant lymphoma (n = 23), and multiple myeloma (n = 3). There were 23 febrile neutropenia episodes and 2 episodes of bacteremia. There were no grade 3 or 4 adverse events; however serum creatinine levels were significantly elevated after garenoxacin administration. The overall prophylactic efficacy of garenoxacin was 50%, and there were no infection-related deaths. Conclusions: Prophylactic use of garenoxacin is effective and safe in patients with hematological malignancies. (Clinical trial registration number: UMIN000004979).

An open-label randomized clinical trial of prophylactic paracetamol coadministered with 7-valent pneumococcal conjugate vaccine and hexavalent diphtheria toxoid, tetanus toxoid, 3-component acellular pertussis, hepatitis B, inactivated poliovirus, and Haemophilus influenzae type b vaccine.

BackgroundIn two clinical trials, low-grade fever was observed more frequently after coadministration than after separate administration of two recommended routine pediatric vaccines. Since fever is an important issue with vaccine tolerability, we performed this open-label study on the efficacy and safety of prophylactic use of paracetamol (acetaminophen, Benuron®) in children administered routine 7-valent pneumococcal conjugate vaccine (PCV-7) coadministered with hexavalent vaccine (diphtheria-tetanus-acellular pertussis-hepatitis B, poliovirus, Haemophilus influenzae type b vaccine [DTPa-HBV-IPV/Hib]) in Germany.MethodsHealthy infants (N = 301) who received a 3-dose infant series of PCV-7 and DTPa-HBV-IPV/Hib plus a toddler dose were randomly assigned 1:1 to prophylactic paracetamol (125 mg or 250 mg suppositories, based on body weight) at vaccination, and at 6–8 hour intervals thereafter, or a control group that received no paracetamol. Rectal temperature and local and other systemic reactions were measured for 4 days post vaccination; adverse events were collected throughout the study.ResultsIn the intent-to-treat population, paracetamol reduced the incidence of fever ≥38°C, but this reduction was only significant for the infant series, with computed efficacy of 43.0% (95% confidence interval [CI]: 17.4, 61.2), and not significant after the toddler dose (efficacy 15.9%; 95% CI: −19.9, 41.3); results were similar in the per protocol (PP) population. Fever >39°C was rare during the infant series, such that there were too few cases for assessment. After the toddler dose, paracetamol effectively reduced fever >39°C, reaching statistical significance in the PP population only (efficacy 79%; 95% CI: 3.9, 97.7). Paracetamol also reduced reactogenicity, but there were few significant differences between groups after any dose. No vaccine-related serious adverse events were reported.ConclusionsParacetamol effectively prevented fever and other reactions, mainly during the infant series. However, as events were generally mild and of no concern in either group our data support current recommendations to administer paracetamol to treat symptoms only and not for routine prophylaxis.Trial registrationNCT00294294

Meta-Analysis of the Effectiveness and Safety of Prophylactic Use of Nimodipine in Patients with an Aneurysmal Subarachnoid Haemorrhage

Cerebral vasospasm is an important cause of poor outcomes in subarachnoid haemorrhage patients. This study was designed to assess the effectiveness and safety of nimodipine in the prevention of cerebral vasospasm in aneurysmal subarachnoid haemorrhage patients. We searched Pubmed, OVID, Embase, the Cochrane library, the stroke clinical trial registry, and the National Science and Technology Library database and collected prospective, randomised, controlled clinical trials of the prophylactic use of nimodipine for aneurismal subarachnoid haemorrhage patients. A meta-analysis was performed on the studies that met the criteria for inclusion. Eight studies met the inclusion criteria, and 1514 patients finished trial observation for the different indicators. Compared with the placebo group, fully recovered (all cases) patients increased 64% in the nimodipine group (P = 0.0002, OR = 1.64, 95 percent CI 1.26 - 2.13, NNT=-1.048), fully recovered or moderately disabled (all cases) patients increased 79 percent (P = 0.0007, OR = 1.79, 95% CI 1.28 - 2.51, NNT = -5.889), patient death (in cerebral vasospasm cases) decreased 74% (P = 0.008, OR = 0.26, 95% CI 0.09 - 0.71, NNT = 2.298), the incidence of symptomatic cerebral vasospasm decreased 46% (P < 0.00001, OR = 0.54, 95% CI 0.42 - 0.69, NNT = 1.952), the incidence of delayed neurological function deficits (all cases) decreased 38% (P < 0.0001, OR = 0.62, 95% CI 0.50 - 0.78, NNT = 1.078), the occurrence of cerebral infarction (on CT scan) decreased 58% (P = 0.001, OR = 0.58, 95% CI 0.42 - 0.81, NNT = 3.314), the occurrence of cerebral infarction (in cerebral vasospasm cases) decreased 65% (P = 0.003, OR = 0.35, 95% CI 0.17 - 0.69, NNT = 3.688), the occurrence of cerebral infarction (all cases) decreased 48% (P < 0.00001, OR = 0.52, 95% CI 0.41 - 0.66, NNT = 1.196), and the difference in recurrent haemorrhage and adverse reactions between the nimodipine and placebo groups was not statistically significant (nimodipine group versus placebo group, recurrent haemorrhage P = 0.15, OR = 0.75, 95% CI 0.50 - 1.11; adverse reaction P = 0.59, OR = 1.13, 95% CI 0.71 - 1.81). Compared with placebo, nimodipine can significantly improve clinical outcomes, as assessed by self-formulated standards and Glasgow outcome scores, and it can significantly reduce the occurrence of symptomatic cerebral vasospasm and delayed neurological function deficits (all cases), as well as cerebral infarction, although the incidence rate of recurrent haemorrhage and adverse reactions is not significantly reduced by nimodipine.

Prophylactic use of noninvasive positive pressure ventilation in post-thoracic surgery patients: A prospective randomized control study.

Prospective randomized controlled study was conducted to explore the effects and safety of prophylactic use of noninvasive positive pressure ventilation (NPPV) in post-thoracic surgery (PTS) patients, especially on the lung re-expansion, lung function change and postoperative pulmonary complications (PPCs). Fifty PTS patients met the inclusion criterion were enrolled in the study. All subjects were randomly divided into conventional treatment (control) group and NPPV group. NPPV group received intermittent NPPV therapy in first three days of PTS. BiPAP ventilator was used with S/T mode in the study. The average IPAP was (13±3.2)cmH(2)O (ranged from 7 to 18 cmH(2)O) and EPAP was 4cmH(2)O. Total ventilation time was (13.5±4.9) hours (ranged from 6.5 to 23 hours). PPCs rate, lung re-expansion, the volume of residual cavity, lung function and tolerance to NPPV were assessed with chest roentgenography, CT scan, lung function testing and clinical evaluation before and one week after surgery. 1. There was no significant difference of total PPCs rate during hospitalization between the two groups (5/23 in NPPV group vs 6/27 in control group, P= 0.967). Multiple factorial logistic regression analysis showed that COPD was a risk factor for PPCs (B=1.705, P=0.027). 2. Compared with control group, NPPV therapy reduced inadequate lung expansion rate (3/23 vs 13/27, P=0.008) and volume of residual cavity calculated with CT scan [(31.9±71.7)ml vs (63.6±78.3)ml, P=0.02]. However, there were no significant difference in the change of lung function parameters after operation between the two groups (all P>0.05). No significant adverse effects of NPPV were found in the present study. In the current study of prophylactic application of NPPV in post-thoracic surgery patients, the use of NPPV resulted in improved lung re-expansion, but had no significant effects on post-operative pulmonary complications and lung functions.

Efficacy and Safety of Prophylactic Use of Darbepoetin Alfa in Patients with Diffuse Large B-Cell Lymphoma (DLBCL) Treated with Immunochemotherapy: Results of the Interim Analysis of the LNH03-6B GELA Study.

Abstract 1701Poster Board I-727 IntroductionThere are still controversies about the impact of erythropoiesis stimulating agents (ESA) on survival of patients with malignancies. The Groupe d'Etude des Lymphomes de l'Adulte (GELA) has conducted a multicentric prospective randomized phase III study to evaluate efficacy and safety of Darbepoetin alfa (DA) in elderly patients with DLBCL treated by immunochemotherapy. Here, we report the results of the planned interim analysis, held after the inclusion of the first 202 patients, with a median follow-up of 24 months.Patients and methods: Patients between 60 and 80 years old with DLBCL and aaIPI ≥ 1 were eligible. They were firstly randomized between two immunochemotherapy regimens combining Rituximab and CHOP given every 2 (R-CHOP14) or 3 weeks (R-CHOP21) for 8 cycles. They were subsequently randomized between an investigational arm with DA (Arm 1) given in order to maintain hemoglobin level between 13 and 15 g/dL and a conventional arm (Arm 2) with usual management of chemotherapy-induced anemia, including red blood cell transfusions and ESA according to usual practices. The objective was to evaluate the efficacy of DA in association with chemotherapy (R-CHOP) as measured by the EFS at 2 years, events being defined as death from any cause, relapse for complete responders and unconfirmed complete responders, progression during or after treatment and changes of therapy during allocated treatment. Secondary objectives were OS, PFS, DFS, response rate and analysis of toxicity. Results202 patients were included and 201 received study treatment ; 90 patients were randomized in DA group and 111 in conventional treatment group. Median age was 72 years. Patients' characteristics were similar in both arms with a slightly higher proportion of patients with aaIPI 2-3 in conventional arm : 68% compared to 56% (p=NS). Median hemoglobin (Hb) level at randomization was 12.2 g/dL. The median Hb level during treatment in DA arm was 11.9 g/dL and 10.7 g/dL in conventional arm respectively. Overall, 41 patients in conventional group received at least one dose of ESA during treatment. Eighteen percent of patients in DA group had at least one episode of Hb > 15 g/dL during treatment compared to 6% in conventional treatment group. Response rate (CR+CRu) after treatment was similar in both groups (69% in DA arm, 72% in conventional arm). Two-year EFS was 59% in DA arm compared with 49% in conventional arm (p=NS). A similar trend was observed for 2-year PFS (61% vs 51%), 2-year DFS (71% vs 56%) and 2-year OS (74% vs 63%) (p=NS for all). Grade 3-4 hematological toxicity was similar in the two groups. In contrast, proportion of patients receiving at least 1 red cell transfusion was higher in conventional arm (49% versus 36%). A total of 288 AEs were reported as serious (130 in DA group and 158 in symptomatic treatment group), concerning 122 patients (61%). Most SAEs were related to infectious complications. The rate of thromboembolic SAEs (composite criteria with pulmonary embolism, venous thrombosis from any site, coronary disease including myocardial infarction and cerebrovascular event) is slightly higher in DA group (13 SAEs) than in conventional arm (9 SAEs). Finally, the number of patients who died because of treatment toxicity was comparable in DA group (6 patients, 7%) and in conventional treatment group (7 patients, 6%). ConclusionsThe results of interim analysis of the LNH 03-6B provide encouraging results about efficacy and safety of a prophylactic use of DA in this population. It should be confirmed by the final analysis of the LNH03-6B trial which is planned in 2010. DisclosuresNo relevant conflicts of interest to declare.

Prophylactic use of ergot alkaloids in the third stage of labour

Previous research has shown that the prophylactic use of uterotonic agents in the third stage of labour reduces postpartum blood loss and moderate to severe postpartum haemorrhage. This is one of a series of systematic reviews assessing the effects of prophylactic use of uterotonic drugs - here, prophylactic ergot alkaloids compared with no uterotonic agents, and different regimens of administration of ergot alkaloids. To determine the effectiveness and safety of prophylactic use of ergot alkaloids in the third stage of labour compared with no uterotonic agents, as well as with different routes or timing of administration for prevention of postpartum haemorrhage. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 December 2006), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2006, Issue 4) and MEDLINE (1966 to December 2006). All randomised or quasi-randomised controlled trials comparing prophylactic ergot alkaloids with no uterotonic agents or comparing different routes or timings of administration of ergot alkaloids in the third stage of labour among women giving birth vaginally. We systematically reviewed the potential studies, considered eligible studies, assessed the validity of each included study and extracted data independently. We included six studies comparing ergot alkaloids with no uterotonic agents, with a total of 1996 women in ergot alkaloids group and 1945 women in placebo or no treatment group. The use of injected ergot alkaloids in the third stage of labour significantly decreased mean blood loss (weighted mean difference -83.03 ml, 95% confidence interval (CI) -99.39 to -66.66 ml) and postpartum haemorrhage of at least 500 ml (relative risk (RR) 0.38, 95% CI 0.21 to 0.69). The risk of retained placenta or manual removal of the placenta, or both, were inconsistent. Ergot alkaloids increased the risk of vomiting (RR 11.81, 95% CI 1.78 to 78.28), elevation of blood pressure (RR 2.60, 95% CI 1.03 to 6.57) and pain after birth requiring analgesia (RR 2.53, 95% CI 1.34 to 4.78). One study compared oral ergometrine with placebo and showed no significant benefit of ergometrine over placebo. No maternal adverse effects were reported. There were no included trials that compared different administration regimens of ergot alkaloids. Prophylactic intramuscular or intravenous injections of ergot alkaloids are effective in reducing blood loss and postpartum haemorrhage, but adverse effects include vomiting, elevation of blood pressure and pain after birth requiring analgesia, particularly with the intravenous route of administration.

Safety of Prophylactic Use of Darbepoetin Alfa in Patients with Diffuse Large B-Cell Lymphoma (DLBCL) Treated with R-CHOP 14 or R-CHOP21: Preliminary Results of the LNH03-6B Randomized GELA Study.

Introduction: Whether erythropoietin (Epo) has an impact on survival of patients (pts) with malignancies is debated. Since Dec 2003, the GELA has conducted a prospective randomized study to evaluate the safety and efficacy of Darbepoetin alfa (DA) in elderly pts with DLBCL treated by immunochemotherapy. In 2005, new recommendations about the use of Epo for patients with chemotherapy induced anemia have been published. Following these recommendations, the protocol was temporarily stopped and a first safety analysis was performed. Here we report the preliminary results on the first 130 enrolled patients.Patients and methods: pts between 66 and 80 years old with DLBCL and aaIPI ≥1 have been enrolled from Dec 2003 to Aug 2005. Pts were firstly randomised between two regimens combining Rituximab and the classical CHOP (Coiffier and al. NEJM 2002) delivered every 2 (R-CHOP14) or 3 weeks (R-CHOP21) for 8 cycles and were subsequently randomised between an investigational arm with DA (Arm 1) given in order to maintain hemoglobin (Hb) level between 13 and 15 g/dL and a conventional arm (Arm 2) with usual treatment of chemotherapy induced anemia, including transfusions and Epo according to usual practices. G-CSF was given according to physicians'decision.Results: 63 pts were randomised in Arm 1 and 67 in Arm 2. Median age is 71 y (66 – 80). Patients'characteristics were similar between arms and the percentage of patients with aaIPI 2–3 is 59%. Mean Hb level at randomisation is 12.2 g/dL (7.1 – 15.6). There rate of deaths during the treatment period is similar between arms (8% and 10%) and mainly related to treatment toxicity or lymphoma progression. The number of serious adverse events of any cause is lower in Arm 1 (96 events) compared to Arm 2 (153 events). Grade 3–4 Hb toxicity is higher in Arm 2 (39% versus 22%, p = NS). 18/63 (29%) patients received red blood cells transfusions in Arm 1 compared to 37/67 (55%) in Arm 2 (p=0.01). The number of patients with at least one episode of febrile neutropenia is lower in Arm 1 as compared to in Arm 2 (23% vs 36%, p = NS). There is no increase of cardiac and vascular events (respectively 9% and 9% in Arm 1 compared to 8% and 10% in Arm 2). The median level of Hb in Arm 1 during treatment is 12.05 g/dL and 10.65 g/dL in Arm 2. Sixteen percent of patients in Arm 1 have had at least one episode of Hb > 15 g/dL during treatment compared to 5% in Arm 2. The rate of thromboembolic events is similar in these patients (2/10) and in those who never have reached this Hb level (7/53). One year after completion of treatment, overall survival (OS) of the entire population is estimated at 74% and event free survival (EFS) at 67%. OS (78% in Arm 1 versus 70% in Arm 2 at 1 year) and EFS (73% in Arm 1 versus 64% in Arm 2 at 1 year) are similar between the two arms.Conclusions: these preliminary results provide encouraging results about the safety of a prophylactic use of Darbepoetin alfa and support the continuation of accrual to draw definite conclusions about safety and also efficacy.

Postoperative aprotinin: Effect on blood loss and transfusion requirements in cardiac operations

Aprotinin has been used increasingly to reduce postoperative blood loss in open heart operations. Although it was reported as safe in earlier studies, the overall safety of prophylactic use has been questioned recently. Because of the potential for complications and the high cost, it will be reasonable to use aprotinin more selectively in the postoperative period. We prospectively studied the effect of postoperative low-dose aprotinin (2 million kallikrein inactivator units [280 mg]) on blood loss and transfusion requirements in patients undergoing cardiopulmonary bypass. Seventy-five patients were randomly assigned to three groups: prophylactic high-dose aprotinin (group 1), postoperative aprotinin (group 2), or a nonmedicated control group (group 3). The three groups were comparable in all demographic and operative variables. Postoperative chest tube drainage was significantly decreased in both aprotinin groups compared with that in the control group (295 mL in group 1 and 325 mL in group 2 versus 411 mL in group 3; p < 0.05). No significant difference was seen between the two aprotinin groups. The use of homologous blood products was significantly less in group 1 and group 2 than in group 3 (1.15 +/- 1.13 U and 1.35 +/- 1.30 U versus 2.55 +/- 1.09 U; p < 0.05). Our results suggest that postoperative aprotinin reduces blood loss and transfusion requirements comparably with prophylactic high-dose aprotinin. Thus, one can restrict its use to patients with excessive postoperative bleeding.