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Prevention of postpartum hemorrhage, safety and efficacy
Abstract
This study was carried out to describe the safety and efficacy of intramuscular syntometrine (oxytocin plus ergometrine) compared to intravenous oxytocin for prevention of postpartum hemorrhage, and the difference between administration at the end of the 2nd stage of labor compared with that after delivery of the placenta.
A prospective study was carried out at Prince Zaid Ben Al-Hussein Hospital, Tafilah, Jordan. Two thousand one hundred and sixty one women delivering singletons during 12 consecutive months were included in our study. Women received either intramuscular syntometrine (oxytocin plus ergometrine) or oxytocin alone. The drugs were used either before or after the 3rd stage of labor, in order to compare their safety and efficacy in prevention of postpartum hemorrhage.
There was no significant difference in the rate of postpartum hemorrhage for syntometrine compared with oxytocin, when used at the end of the 2nd stage of labor (odds ratio 1.08, 95% confidence interval 0.72-1.63) or after the 3rd stage (odds ratio 0.93, 95% confidence interval 0.65-1.34). The patients receiving oxytocics at the end of the 2nd stage of labor had significantly lower rates of postpartum hemorrhage, for both syntometrine (odds ratio 0.86, 95% confidence interval 0.59-0.1.12) and Oxytocin (odds ratio 0.59, 95% confidence interval 0.39-0.88), compared with those treated after the 3rd stage.
Oxytocin alone is as effective as the use of syntometrine (ergometrine plus oxytocin) in the prevention of postpartum hemorrhage, but associated with significantly fewer maternal side effects. Oxytocics administered after the 2nd stage of labor compared with after the 3rd stage of labor (placental expulsion) are associated with a significantly fewer rate of postpartum bleeding.
... Steen found that 6,573 patients received treatment in studies that eventually were retracted for fraud. One 2001 article in the Saudi Medical Journal included 2,161 women being treated for postpartum bleeding (1). And while most of the papers Steen analyzed appeared in publications with low impact factors, likely minimizing their influence on future research, two appeared in The Lancet and JAMA, the latter a 2008 study of a purported breakthrough in the treatment of liver cancer that turned out to be bogus (8). ...
The retraction is receiving a growing amount of attention as an important event in scientific and scholarly publishing. Not only are some journals becoming increasingly open in their handling of the articles they withdraw-allowing researchers to gain important insights into the work of their colleagues-but scholars, too, have greater access to the reasons for retractions, information that is dramatically reshaping our understanding of such events. As this article will demonstrate, recent research has inverted the accepted lore about why retractions happen and their impact.
... participants. Seven [6][7][8][9][10][11][12] of these were retracted for fraud; however, the term 'fraud' encompassed a wide range of activities, and only two trials were suspected of falsifying data based on the six retraction statements available [10,11]. ...
On-site source data verification is a common and expensive activity, with little evidence that it is worthwhile. Central statistical monitoring (CSM) is a cheaper alternative, where data checks are performed by the coordinating centre, avoiding the need to visit all sites. Several publications have suggested methods for CSM; however, few have described their use in real trials.
R-programs were created to check data at either the subject level (7 tests within 3 programs) or site level (9 tests within 8 programs) using previously described methods or new ones we developed. These aimed to find possible data errors such as outliers, incorrect dates, or anomalous data patterns; digit preference, values too close or too far from the means, unusual correlation structures, extreme variances which may indicate fraud or procedural errors and under-reporting of adverse events. The methods were applied to three trials, one of which had closed and has been published, one in follow-up, and a third to which fabricated data were added. We examined how well the methods work, discussing their strengths and limitations.
The R-programs produced simple tables or easy-to-read figures. Few data errors were found in the first two trials, and those added to the third were easily detected. The programs were able to identify patients with outliers based on single or multiple variables. They also detected (1) fabricated patients, generated to have values too close to the multivariate mean, or with too low variances in repeated measurements, and (2) sites which had unusual correlation structures or too few adverse events. Some methods were unreliable if applied to centres with few patients or if data were fabricated in a way which did not fit the assumptions used to create the programs. Outputs from the R-programs are interpreted using examples.
Detecting data errors is relatively straightforward; however, there are several limitations in the detection of fraud: some programs cannot be applied to small trials or to centres with few patients (<10) and data falsified in a manner which does not fit the program's assumptions may not be detected. In addition, many tests require a visual assessment of the output (showing flagged participants or sites), before data queries are made or on-site visits performed.
CSM is a worthwhile alternative to on-site data checking and may be used to limit the number of site visits by targeting only sites which are picked up by the programs. We summarise the methods, show how they are implemented and that they can be easy to interpret. The methods can identify incorrect or unusual data for a trial subject, or centres where the data considered together are too different to other centres and therefore should be reviewed, possibly through an on-site visit.
... Whilst many of the studies were restricted to blood loss after delivery, three studies measured blood loss both during and after delivery171819; two of these studies stated that they were measuring PPH [18,19]. Thirty-one studies stated that they measured PPH but did not specify the timing of blood loss measurement (for example: [20,21]). A further four studies referred to the outcome as ''blood loss'' without stating specifically that they were measuring PPH or specifying the timings of blood loss measurement22232425, and two studies measured blood loss at delivery [26,27]. ...
To provide regional estimates of the prevalence of maternal haemorrhage and explore the effect of methodological differences between studies on any observed regional variation.
We conducted a systematic review of the prevalence of maternal haemorrhage, defined as blood loss greater than or equal to 1) 500 ml or 2) 1000 ml in the antepartum, intrapartum or postpartum period. We obtained regional estimates of the prevalence of maternal and severe maternal haemorrhage by conducting meta-analyses and used meta-regression to explore potential sources of between-study heterogeneity.
No studies reported the prevalence of antepartum haemorrhage (APH) according to our definitions. The prevalence of postpartum haemorrhage (PPH) (blood loss ≥500 ml) ranged from 7.2% in Oceania to 25.7% in Africa. The prevalence of severe PPH (blood loss ≥1000 ml) was highest in Africa at 5.1% and lowest in Asia at 1.9%. There was strong evidence of between-study heterogeneity in the prevalence of PPH and severe PPH in most regions. Meta-regression analyses suggested that region and method of measurement of blood loss influenced prevalence estimates for both PPH and severe PPH. The regional patterns changed after adjusting for the other predictors of PPH indicating that, compared with European women, Asian women have a lower prevalence of PPH.
We found evidence that Asian women have a very low prevalence of PPH compared with women in Europe. However, more reliable estimates will only be obtained with the standardisation of the measurement of PPH so that the data from different regions are comparable.
Objective: To assess the effects of injection syntocinon vs injection syntometrine in reducing the risks of post partum haemorrhage and to observe the side effects after the use of two drugs. Study Design: Case control study. Setting & Duration: Jinnah Postgraduate Medical Centre in Department of Gynae and Obstetrics from January 2002 to December 2002. Methodology: Three hundred patients were selected by non-probability convenience sampling. This study was conducted on the patients admitted in labour room with singleton pregnancy in whom vaginal delivery was imminent the patients were grouped in three categories. Group I comprised of 150 patients who received injection syntocinon 5 unit I/V alone. Group II comprised of 150 patients who received injection syntocinon 5 unit and injection ergometrine 0.5 mg. I/M the injection was given after explusion of placenta. Blood loss during delivery was estimated by measuring the amount of blood clots and weighing the towels and swabs soaked befor and after delivery any delayed haemorrhage within in the first 24 hours after delivery was recorded. Maternal blood pressure was measured immediately after delivery. The side effects like nausea, vomiting and headache were noted from time ranging 1-2 hour after delivery. Results: The rate 46.7% of blood loss of 500 ml in syntocinon group was observed significantly high as compared with that of tbe rate 36.7% of syntometrine at PC 0.05 the rate of adverse effect in group I of syntocinon was 8% and 17.3% in group II of syntometrine. The data revealed a significantly high rate (Z=2.39 P=0.008) of adverse effects in syntometrine group of patients then syntocinon group at PC 0.05. Conclusion: Oxytocin alone is as effective as the use of syntometrine in prevention of post-partum haemorrhage but associated with significantly fewer maternal side effects.
Recent studies have suggested an increase in the number of retracted scientific publications. It is unclear how broadly the issue of misleading and fraudulent publications pertains to retractions of drug therapy studies. Therefore, we sought to determine the trends and factors associated with retracted publications in drug therapy literature. A PubMed search was conducted to identify retracted drug therapy articles published from 2000-2011. Articles were grouped according to reason for retraction, which was classified as scientific misconduct or error. Scientific misconduct was further divided into data fabrication, data falsification, questions of data veracity, unethical author conduct, and plagiarism. Error was defined as duplicate publication, scientific mistake, journal error, or unstated reasons. Additional data were extracted from the retracted articles, including type of article, funding source, author information, therapeutic area, and retraction issue. A total of 742 retractions were identified from 2000-2011 in the general biomedical literature, and 102 drug studies met our inclusion criteria. Of these, 73 articles (72%) were retracted for a reason classified as scientific misconduct, whereas 29 articles (28%) were retracted for error. Among the 73 articles classified as scientific misconduct, those classified as unethical author conduct (32 articles [44%]) and data fabrication (24 articles [33%]) constituted the majority. The median time from publication of the original article to retraction was 31 months (range 1-130). Fifty percent of retracted articles did not state a funding source, whereas pharmaceutical manufacturer funding accounted for only 13 articles (13%) analyzed. Many retractions were due to repeat offenses by a small number of authors, with nearly 40% of the retracted studies associated with two individuals. We found that a greater proportion of drug therapy articles were retracted for reasons of misconduct and fraud compared with other biomedical studies. It is important for health care practitioners to monitor the literature for retractions so that recommendations for drug therapy and patient management may be modified accordingly.
Clinical papers so flawed that they are eventually retracted may put patients at risk. Patient risk could arise in a retracted primary study or in any secondary study that draws ideas or inspiration from a primary study.
To determine how many patients were put at risk, we evaluated 788 retracted English-language papers published from 2000 to 2010, describing new research with humans or freshly derived human material. These primary papers-together with all secondary studies citing them-were evaluated using ISI Web of Knowledge. Excluded from study were 468 basic science papers not studying fresh human material; 88 reviews presenting older data; 22 case reports; 7 papers retracted for journal error and 23 papers unavailable on Web of Knowledge. Overall, 180 retracted primary papers (22.8%) met the inclusion criteria. Subjects enrolled and patients treated in 180 primary studies and 851 secondary studies were combined.
Retracted papers were cited over 5000 times, with 93% of citations being research related, suggesting that ideas promulgated in retracted papers can influence subsequent research. Over 28 000 subjects were enrolled-and 9189 patients were treated-in 180 retracted primary studies. Over 400 000 subjects were enrolled-and 70 501 patients were treated-in 851 secondary studies which cited a retracted paper. Papers retracted for fraud (n=70) treated more patients per study (p<0.01) than papers retracted for error (n=110).
Many patients are put at risk by retracted studies. These are conservative estimates, as only patients enrolled in published clinical studies were tallied.
Postpartum haemorrhage (PPH) is an important cause of maternal mortality. We conducted a systematic review of the prevalence of PPH with the objective of evaluating its magnitude both globally and in different regions and settings: global figures, as well as regional, country and provincial variations, are likely to exist but are currently unknown. We used prespecified criteria to select databases, recorded the database characteristics and assessed their methodological quality. After establishing PPH (>or=500 mL blood loss) and severe PPH (SSPH) (>or=1000 mL blood loss) as main outcomes, we found 120 datasets (involving a total of 3,815,034 women) that reported PPH and 70 datasets (505,379 women) that reported SPPH in the primary analysis. The prevalence of PPH and SPPH is approximately 6% and 1.86% of all deliveries, respectively, with a wide variation across regions of the world. The figures we obtained give a rough estimate of the prevalence of PPH and suggest the existence of some variations. For a reliable picture of PPH worldwide - its magnitude, distribution and consequences - a global survey tackling this condition is necessary.
Objective To compare the effect of intramuscular Syntometrine and Syntocinon in the management of the third stage of labour.
Design A randomised double blind prospective study.
Setting Department of Obstetrics and Gynaecology, Prince of Wales Hospital, Hong Kong.
Subjects One thousand consecutive patients with singleton pregnancy and vaginal delivery in February and March 1993.
Results The use of Syntometrine in the management of the third stage not only reduced the blood loss after delivery but was associated with a 40% reduction in the risk of postpartum haemorrhage (odds ratio 0.60; 95% CI 0.21–0.88), and the need for repeat oxytocic injections (odds ratio of 0.63; 95% CI 0.44–089). The two drugs did not differ in their effect on the duration of the third stage. However, the incidence of manual removal of the placenta was higher when Syntometrine was used (odds ratio 3.7; 95% CI 1.03–123), although the overall incidence remained low. Side effects from both drugs, such as nausea, vomiting, headache and hypertension, were uncommon.
Conclusion Intramuscular Syntometrine is a better choice than Syntocinon in the management of the third stage of labour.
Syntometrine, a combination of ergometrine and oxytocin, is used almost universally in Great Britain at the end of the second stage of labour to reduce blood loss and prevent postpartum haemorrhage. In the United States of America, ergometrine has rarely if ever been used in recent years for this purpose as it is considered to be neither the safest nor the most effective drug for third stage management. A review of the literature suggests that the danger of ergometrine compared with oxytocin has been exaggerated.
In a series of 2102 cases, Syntometrine has been compared with oxytocin. Intramuscular oxytocin is less effective in reducing postpartum blood loss than intramuscular Syntometrine. The treatment of choice is intravenous oxytocin, but there are practical difficulties in routinely giving an intravenous injection during the second stage of labour, unless the patient already has an intravenous dextrose drip. So, patients who have a drip running should be given intravenous oxytocin: those who have not, should be given intramuscular Syntometrine
Prophylactic use of oxytocics reduces the risk of postpartum haemorrhage by about 40%. The analysis presented in this paper assesses which oxytocic preparation is associated with the least risk of postpartum haemorrhage and examines the relative effects of different preparations on the length of the third stage, the risk of manual removal of the placenta, blood pressure and other side-effects. A mixture of oxytocin and ergometrine (Syntometrine) appears to be the safest and most effective prophylactic of the alternatives which have been compared, but the quality of the evidence is not satisfactory. There is scope for a randomized comparison of Syntometrine with oxytocin to obtain unbiased and more precise estimates of their relative effects on postpartum haemorrhage, blood pressure and unpleasant side-effects.
Prophylactic use of oxytocics reduces the risk of postpartum haemorrhage by about 40%. The analysis presented in this paper assesses which oxytocic preparation is associated with the least risk of postpartum haemorrhage and examines the relative effects of different preparations on the length of the third stage, the risk of manual removal of the placenta, blood pressure and other side-effects. A mixture of oxytocin and ergometrine (Syntometrine) appears to be the safest and most effective prophylactic of the alternatives which have been compared, but the quality of the evidence is not satisfactory. There is scope for a randomized comparison of Syntometrine with oxytocin to obtain unbiased and more precise estimates of their relative effects on postpartum haemorrhage, blood pressure and unpleasant side-effects.
To compare the effect of intramuscular Syntometrine and Syntocinon in the management of the third stage of labour.
A randomised double blind prospective study.
Department of Obstetrics and Gynaecology, Prince of Wales Hospital, Hong Kong.
One thousand consecutive patients with singleton pregnancy and vaginal delivery in February and March 1993.
The use of Syntometrine in the management of the third stage not only reduced the blood loss after delivery but was associated with a 40% reduction in the risk of postpartum haemorrhage (odds ratio 0.60; 95% CI 0.21-0.88), and the need for repeat oxytocic injections (odds ratio of 0.63; 95% CI 0.44-0.89). The two drugs did not differ in their effect on the duration of the third stage. However, the incidence of manual removal of the placenta was higher when Syntometrine was used (odds ratio 3.7; 95% CI 1.03-12.5), although the overall incidence remained low. Side effects from both drugs, such as nausea, vomiting, headache and hypertension, were uncommon.
Intramuscular Syntometrine is a better choice than Syntocinon in the management of the third stage of labour.
Standpoint of reducing the amount of bleeding, the value of administering an oxytocic agent intravenously at the end of the second stage of labour has long been established (Adair et al., 1935). It has also repeatedly been shown that, although both are safe, ergometrine is more effective than oxytocin (Lister, 1950).