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International Journal of Environmental... Jul 2022Due to the multifactorial etiology of scoliosis, a comprehensive treatment plan is essential for conservative management. Physiotherapeutic scoliosis-specific exercise... (Review)
Review
Physiotherapeutic Scoliosis-Specific Exercise Methodologies Used for Conservative Treatment of Adolescent Idiopathic Scoliosis, and Their Effectiveness: An Extended Literature Review of Current Research and Practice.
Due to the multifactorial etiology of scoliosis, a comprehensive treatment plan is essential for conservative management. Physiotherapeutic scoliosis-specific exercise (PSSE) methods have lately gained popularity for the conservative treatment of scoliosis. The aim of this study was to analyze the PSSE methodologies used for conservative treatment of adolescent idiopathic scoliosis (AIS), as well as their effectiveness. The study was based on an extended literature search conducted in the PubMed, Google Scholar, PEDro, eLABA, and BioMed Central databases. A total of 123 articles were selected for this study (including articles overviewed in systematic reviews and meta-analyses) after applying the inclusion criteria. The study revealed that inappropriate management of AIS could result in serious health problems. Conservative interventions that aid in stabilizing spine curvature and improving esthetics are preferred for scoliosis treatment. Bracing has traditionally been the mainstay of treatment, but growing evidence suggests that PSSE physiotherapy allows effective management of idiopathic adolescent scoliosis. Currently, there are the following PSSE physiotherapy schools in Europe: Schroth, SEAS, BSPTS, FED, FITS, Lyon, Side Shift, and DoboMed. The methodologies of these schools are similar, in that they focus on applying corrective exercises in three planes, developing stability and balance, breathing exercises, and posture awareness. Although high-quality research supporting the effectiveness of PSSE physiotherapy in the treatment of AIS is lacking, existing evidence indicates that PSSE physiotherapy helps to stabilize spinal deformity and improve patients' quality of life. Among the abovementioned methodologies, Schroth is the most widely studied and has been proven to be effective. However, both SEAS and BSPTS effectively stabilize and even reduce the Cobb angle of scoliosis. Data supporting the validity of other methodologies are very limited. Only the Schroth method significantly reduces the angle of trunk rotation, while both SEAS and Schroth methods greatly improve the quality of life indicators. In any case, the available evidence is insufficient to confirm the advantage of one specific physiotherapy technique over others.
Topics: Adolescent; Conservative Treatment; Exercise Therapy; Humans; Quality of Life; Scoliosis; Systematic Reviews as Topic; Treatment Outcome
PubMed: 35954620
DOI: 10.3390/ijerph19159240 -
Journal of Clinical Nursing Jul 2019To explore nursing interventions used among patients with cancer and summarise the results of their effectiveness. The ultimate goal was to improve the quality of care... (Review)
Review
AIMS AND OBJECTIVES
To explore nursing interventions used among patients with cancer and summarise the results of their effectiveness. The ultimate goal was to improve the quality of care and provide best evidence for clinicians to refer to while developing effective nursing interventions.
BACKGROUND
Nursing interventions refer to actions that nurses take with the aim of improving the well-being of people with cancer-related health and care needs. A plethora of systematic reviews has been conducted in this research area, although with scattered results. We conducted a comprehensive review to identify and summarise the existing evidence.
METHODS
This overview of systematic reviews adheres to the PRISMA guidelines. The PubMed, CINAHL, MEDLINE and Scopus databases were searched. Nine reviews reporting findings from 112 original studies published 2007-2017 met the selection criteria. The results of intervention effectiveness were analysed using descriptive quantification and a narrative summary of the quantitative data.
RESULTS
The effectiveness of educational nursing interventions was inconsistent on quality of life (QoL), attitudes, anxiety and distress, but positive on level of knowledge, symptom severity, sleep and uncertainty. Psychosocial nursing interventions had a significant effect on spiritual well-being, meaning of life, fatigue and sleep. Psychological nursing interventions reduced cancer-related fatigue. Nursing interventions supporting patients' coping had a significant impact on anxiety, distress, fatigue, sleep, dyspnoea and functional ability. Activity-based interventions may prevent cancer-related fatigue.
CONCLUSIONS
Nursing interventions achieved significant physical and psychological effects on the lives of patients with cancer. Multidimensional nature of interventions by combining different elements reinforces the effect. Priorities for future research include identifying the most beneficial components of these interventions.
RELEVANCE TO CLINICAL PRACTICE
Implementation of these nursing interventions into clinical practice is important to improve patients' knowledge and QoL as well as reducing various symptoms and side effects related to cancer and its treatment.
Topics: Adaptation, Psychological; Anxiety; Fatigue; Humans; Neoplasms; Oncology Nursing; Quality of Life; Systematic Reviews as Topic
PubMed: 30585667
DOI: 10.1111/jocn.14762 -
Parkinsonism & Related Disorders Jan 2016Although Deep Brain Stimulation (DBS) is an established treatment for Parkinson's disease (PD), there are still limitations in terms of effectivity, side-effects and... (Review)
Review
Although Deep Brain Stimulation (DBS) is an established treatment for Parkinson's disease (PD), there are still limitations in terms of effectivity, side-effects and battery consumption. One of the reasons for this may be that not only pathological but also physiological neural activity can be suppressed whilst stimulating. For this reason, adaptive DBS (aDBS), where stimulation is applied according to the level of pathological activity, might be advantageous. Initial studies of aDBS demonstrate effectiveness in PD, but there are still many questions to be answered before aDBS can be applied clinically. Here we discuss the feedback signals and stimulation algorithms involved in adaptive stimulation in PD and sketch a potential road-map towards clinical application.
Topics: Animals; Brain-Computer Interfaces; Deep Brain Stimulation; Humans; Hypokinesia; Parkinson Disease; Subthalamic Nucleus; Tremor
PubMed: 26411502
DOI: 10.1016/j.parkreldis.2015.09.028 -
American Family Physician Aug 2008Skeletal muscle relaxants are widely used in treating musculoskeletal conditions. However, evidence of their effectiveness consists mainly of studies with poor... (Review)
Review
Skeletal muscle relaxants are widely used in treating musculoskeletal conditions. However, evidence of their effectiveness consists mainly of studies with poor methodologic design. In addition, these drugs have not been proven to be superior to acetaminophen or nonsteroidal anti-inflammatory drugs for low back pain. Systematic reviews and meta-analyses support using skeletal muscle relaxants for short-term relief of acute low back pain when nonsteroidal anti-inflammatory drugs or acetaminophen are not effective or tolerated. Comparison studies have not shown one skeletal muscle relaxant to be superior to another. Cyclobenzaprine is the most heavily studied and has been shown to be effective for various musculoskeletal conditions. The sedative properties of tizanidine and cyclobenzaprine may benefit patients with insomnia caused by severe muscle spasms. Methocarbamol and metaxalone are less sedating, although effectiveness evidence is limited. Adverse effects, particularly dizziness and drowsiness, are consistently reported with all skeletal muscle relaxants. The potential adverse effects should be communicated clearly to the patient. Because of limited comparable effectiveness data, choice of agent should be based on side-effect profile, patient preference, abuse potential, and possible drug interactions.
Topics: Back Pain; Fibromyalgia; Humans; Neck Pain; Neuromuscular Agents; Treatment Outcome
PubMed: 18711953
DOI: No ID Found -
Bundesgesundheitsblatt,... Jul 2021For a few decades, a decrease in the caries burden in all age groups has been observed in Germany. The regular use of fluoride preparations is described as the main... (Review)
Review
For a few decades, a decrease in the caries burden in all age groups has been observed in Germany. The regular use of fluoride preparations is described as the main reason for the caries decline. It is well established that topical fluoride application directly to the tooth surfaces in the oral cavity, in particular fluoride-containing toothpastes and fluoride varnishes, is responsible for the decline. Several mechanisms of action, such as the formation of a calcium fluoride layer, remineralization, and the effects on bacterial plaque, were determined to be responsible for the overall clinical effect. All these mechanisms can be effective on enamel and root dentin in patients of all ages. There is a dose-response relationship between the fluoride concentration in the applied preparations and the average caries reduction achieved.There are no general toxicological concerns about topical fluoride application. Fluoride toothpastes should be used from the eruption of the first deciduous tooth. The amount of toothpaste used should be limited to the recommended volumes to avoid the development of enamel fluorosis. The professionally performed application of highly concentrated fluoride varnishes, in addition to having a high caries-inhibiting effectiveness, also exhibits advantages in cases of increased caries risk and existing demineralization. This is also the case for the application on root dentin, where significant primary and secondary preventive effects have been demonstrated by application of highly concentrated fluoride preparations.
Topics: Cariostatic Agents; Dental Caries; Dental Caries Susceptibility; Fluorides; Germany; Humans; Toothpastes
PubMed: 34115151
DOI: 10.1007/s00103-021-03347-4 -
Reproductive Health Jan 2021Unintended pregnancies (UIP) have a significant impact on health of women and the health budget of countries. Contraception is an effective way to prevent UIPs. The... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Unintended pregnancies (UIP) have a significant impact on health of women and the health budget of countries. Contraception is an effective way to prevent UIPs. The study objective was to collate evidence on clinical effectiveness of etonogestrel subdermal implant (ESI), continuation rate and side effect profile among eligible women of reproductive age group, as compared to levonorgestrel intrauterine system (LNG-IUS), copper intrauterine device (Cu-IUD) and depot medroxy progesterone acetate injections; other types of contraceptive implants were excluded as comparators.
METHODS
The protocol of the systematic review was registered in Prospero (registration number: CRD42018116580). MEDLINE via PubMed, Cochrane library and web of science were the electronic databases searched. A search strategy was formulated and studies from 1998 to 2019 were included. Clinical trial registries and grey literature search was done. Critical assessment of included studies was done using appropriate tools. A qualitative synthesis of included studies was done and a meta-analysis was conducted in RevMan software for continuation rates of ESI as compared to other long acting reversible contraceptives (LARC) e.g. LNG IUS and Cu-IUD.
RESULTS
The search yielded 23,545 studies. After excluding 467 duplicates, 23,078 titles were screened and 51 studies were included for the review. Eight of the 15 studies reporting clinical effectiveness reported 100% effectiveness and overall pearl index ranged from 0 to 1.4. One-year continuation rates ranged from 57-97%; 44-95% at the end of second year and 25-78% by 3 years of use. Abnormal menstruation was the most commonly reported side effect. There was no significant difference in bone mineral density at 1 year follow-up. The meta-analyses showed that odds ratio (OR) of 1-year continuation rate was 1.55 (1.36, 1.76) for LNG-IUS vs. ESI and 1.34 (1.13, 1.58) for copper-IUD vs. ESI; showing that continuation rates at the end of one-year were higher in LNG-IUS and copper-IUD as compared to ESI.
CONCLUSION
ESI is clinically effective and safe contraceptive method to use, yet 1-year continuation rates are lower as compared to LNG-IUS and copper-IUD, mostly attributed to the disturbances in the menstruation.
Topics: Adolescent; Adult; Contraception Behavior; Contraceptive Agents, Female; Contraceptive Agents, Hormonal; Desogestrel; Female; Humans; Intrauterine Devices, Copper; Pregnancy; Treatment Outcome; Young Adult
PubMed: 33407632
DOI: 10.1186/s12978-020-01054-y -
Nutrients Sep 2022Attention Deficit/Hyperactivity Disorder is the most prevalent neurodevelopmental disorder worldwide. Choice treatment includes psychostimulants, but parents tend to be... (Clinical Trial)
Clinical Trial
Attention Deficit/Hyperactivity Disorder is the most prevalent neurodevelopmental disorder worldwide. Choice treatment includes psychostimulants, but parents tend to be reluctant to administer them due to side effects, and alternatives are needed. Saffron extract is a natural stimulant that has been proven safe and effective for treating a variety of mental disorders. This study compares the efficacy of saffron and the usual treatment with methylphenidate, using objective and pen-and-paper tests. We performed a non-randomized clinical trial with two groups, methylphenidate ( = 27) and saffron ( = 36), in children and adolescents aged 7 to 17. Results show that the efficacy of saffron is comparable to that of methylphenidate. Saffron is more effective for treating hyperactivity symptoms, while methylphenidate is more effective for inattention symptoms.
Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Crocus; Humans; Methylphenidate; Parents
PubMed: 36235697
DOI: 10.3390/nu14194046 -
The Cochrane Database of Systematic... Apr 2018Postpartum haemorrhage (PPH) is the leading cause of maternal mortality worldwide. Prophylactic uterotonic drugs can prevent PPH, and are routinely recommended. There... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Postpartum haemorrhage (PPH) is the leading cause of maternal mortality worldwide. Prophylactic uterotonic drugs can prevent PPH, and are routinely recommended. There are several uterotonic drugs for preventing PPH but it is still debatable which drug is best.
OBJECTIVES
To identify the most effective uterotonic drug(s) to prevent PPH, and generate a ranking according to their effectiveness and side-effect profile.
SEARCH METHODS
We searched Cochrane Pregnancy and Childbirth's Trials Register (1 June 2015), ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) for unpublished trial reports (30 June 2015) and reference lists of retrieved studies.
SELECTION CRITERIA
All randomised controlled comparisons or cluster trials of effectiveness or side-effects of uterotonic drugs for preventing PPH.Quasi-randomised trials and cross-over trials are not eligible for inclusion in this review.
DATA COLLECTION AND ANALYSIS
At least three review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. We estimated the relative effects and rankings for preventing PPH ≥ 500 mL and PPH ≥ 1000 mL as primary outcomes. We performed pairwise meta-analyses and network meta-analysis to determine the relative effects and rankings of all available drugs. We stratified our primary outcomes according to mode of birth, prior risk of PPH, healthcare setting, dosage, regimen and route of drug administration, to detect subgroup effects.The absolute risks in the oxytocin are based on meta-analyses of proportions from the studies included in this review and the risks in the intervention groups were based on the assumed risk in the oxytocin group and the relative effects of the interventions.
MAIN RESULTS
This network meta-analysis included 140 randomised trials with data from 88,947 women. There are two large ongoing studies. The trials were mostly carried out in hospital settings and recruited women who were predominantly more than 37 weeks of gestation having a vaginal birth. The majority of trials were assessed to have uncertain risk of bias due to poor reporting of study design. This primarily impacted on our confidence in comparisons involving carbetocin trials more than other uterotonics.The three most effective drugs for prevention of PPH ≥ 500 mL were ergometrine plus oxytocin combination, carbetocin, and misoprostol plus oxytocin combination. These three options were more effective at preventing PPH ≥ 500 mL compared with oxytocin, the drug currently recommended by the WHO (ergometrine plus oxytocin risk ratio (RR) 0.69 (95% confidence interval (CI) 0.57 to 0.83), moderate-quality evidence; carbetocin RR 0.72 (95% CI 0.52 to 1.00), very low-quality evidence; misoprostol plus oxytocin RR 0.73 (95% CI 0.60 to 0.90), moderate-quality evidence). Based on these results, about 10.5% women given oxytocin would experience a PPH of ≥ 500 mL compared with 7.2% given ergometrine plus oxytocin combination, 7.6% given carbetocin, and 7.7% given misoprostol plus oxytocin. Oxytocin was ranked fourth with close to 0% cumulative probability of being ranked in the top three for PPH ≥ 500 mL.The outcomes and rankings for the outcome of PPH ≥ 1000 mL were similar to those of PPH ≥ 500 mL. with the evidence for ergometrine plus oxytocin combination being more effective than oxytocin (RR 0.77 (95% CI 0.61 to 0.95), high-quality evidence) being more certain than that for carbetocin (RR 0.70 (95% CI 0.38 to 1.28), low-quality evidence), or misoprostol plus oxytocin combination (RR 0.90 (95% CI 0.72 to 1.14), moderate-quality evidence)There were no meaningful differences between all drugs for maternal deaths or severe morbidity as these outcomes were so rare in the included randomised trials.Two combination regimens had the poorest rankings for side-effects. Specifically, the ergometrine plus oxytocin combination had the higher risk for vomiting (RR 3.10 (95% CI 2.11 to 4.56), high-quality evidence; 1.9% versus 0.6%) and hypertension [RR 1.77 (95% CI 0.55 to 5.66), low-quality evidence; 1.2% versus 0.7%), while the misoprostol plus oxytocin combination had the higher risk for fever (RR 3.18 (95% CI 2.22 to 4.55), moderate-quality evidence; 11.4% versus 3.6%) when compared with oxytocin. Carbetocin had similar risk for side-effects compared with oxytocin although the quality evidence was very low for vomiting and for fever, and was low for hypertension.
AUTHORS' CONCLUSIONS
Ergometrine plus oxytocin combination, carbetocin, and misoprostol plus oxytocin combination were more effective for preventing PPH ≥ 500 mL than the current standard oxytocin. Ergometrine plus oxytocin combination was more effective for preventing PPH ≥ 1000 mL than oxytocin. Misoprostol plus oxytocin combination evidence is less consistent and may relate to different routes and doses of misoprostol used in the studies. Carbetocin had the most favourable side-effect profile amongst the top three options; however, most carbetocin trials were small and at high risk of bias.Amongst the 11 ongoing studies listed in this review there are two key studies that will inform a future update of this review. The first is a WHO-led multi-centre study comparing the effectiveness of a room temperature stable carbetocin versus oxytocin (administered intramuscularly) for preventing PPH in women having a vaginal birth. The trial includes around 30,000 women from 10 countries. The other is a UK-based trial recruiting more than 6000 women to a three-arm trial comparing carbetocin, oxytocin and ergometrine plus oxytocin combination. Both trials are expected to report in 2018.Consultation with our consumer group demonstrated the need for more research into PPH outcomes identified as priorities for women and their families, such as women's views regarding the drugs used, clinical signs of excessive blood loss, neonatal unit admissions and breastfeeding at discharge. To date, trials have rarely investigated these outcomes. Consumers also considered the side-effects of uterotonic drugs to be important but these were often not reported. A forthcoming set of core outcomes relating to PPH will identify outcomes to prioritise in trial reporting and will inform futures updates of this review. We urge all trialists to consider measuring these outcomes for each drug in all future randomised trials. Lastly, future evidence synthesis research could compare the effects of different dosages and routes of administration for the most effective drugs.
Topics: Drug Therapy, Combination; Ergonovine; Female; Fever; Humans; Hypertension; Misoprostol; Network Meta-Analysis; Oxytocics; Oxytocin; Postpartum Hemorrhage; Vomiting
PubMed: 29693726
DOI: 10.1002/14651858.CD011689.pub2 -
The Cochrane Database of Systematic... Jun 2013Premenstrual syndrome (PMS) is a common cause of physical, psychological and social problems in women of reproductive age. The key characteristic of PMS is the timing of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Premenstrual syndrome (PMS) is a common cause of physical, psychological and social problems in women of reproductive age. The key characteristic of PMS is the timing of symptoms, which occur only during the two weeks leading up to menstruation (the luteal phase of the menstrual cycle). Selective serotonin reuptake inhibitors (SSRIs) are increasingly used as first line therapy for PMS. SSRIs can be taken either in the luteal phase or else continuously (every day). SSRIs are generally considered to be effective for reducing premenstrual symptoms but they can cause adverse effects.
OBJECTIVES
The objective of this review was to evaluate the effectiveness and safety of SSRIs for treating premenstrual syndrome.
SEARCH METHODS
Electronic searches for relevant randomised controlled trials (RCTs) were undertaken in the Cochrane Menstrual Disorders and Subfertility Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, PsycINFO, and CINAHL (February 2013). Where insufficient data were presented in a report, attempts were made to contact the original authors for further details.
SELECTION CRITERIA
Studies were considered in which women with a prospective diagnosis of PMS, PMDD or late luteal phase dysphoric disorder (LPDD) were randomised to receive SSRIs or placebo for the treatment of premenstrual syndrome.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected the studies, assessed eligible studies for risk of bias, and extracted data on premenstrual symptoms and adverse effects. Studies were pooled using random-effects models. Standardised mean differences (SMDs) with 95% confidence intervals (CIs) were calculated for premenstrual symptom scores, using separate analyses for different types of continuous data (that is end scores and change scores). Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for dichotomous outcomes. Analyses were stratified by type of drug administration (luteal or continuous) and by drug dose (low, medium, or high). We calculated the number of women who would need to be taking a moderate dose of SSRI in order to cause one additional adverse event (number needed to harm: NNH). The overall quality of the evidence for the main findings was assessed using the GRADE working group methods.
MAIN RESULTS
Thirty-one RCTs were included in the review. They compared fluoxetine, paroxetine, sertraline, escitalopram and citalopram versus placebo. SSRIs reduced overall self-rated symptoms significantly more effectively than placebo. The effect size was moderate when studies reporting end scores were pooled (for moderate dose SSRIs: SMD -0.65, 95% CI -0.46 to -0.84, nine studies, 1276 women; moderate heterogeneity (I(2) = 58%), low quality evidence). The effect size was small when studies reporting change scores were pooled (for moderate dose SSRIs: SMD -0.36, 95% CI -0.20 to -0.51, four studies, 657 women; low heterogeneity (I(2)=29%), moderate quality evidence).SSRIs were effective for symptom relief whether taken only in the luteal phase or continuously, with no clear evidence of a difference in effectiveness between these modes of administration. However, few studies directly compared luteal and continuous regimens and more evidence is needed on this question.Withdrawals due to adverse effects were significantly more likely to occur in the SSRI group (moderate dose: OR 2.55, 95% CI 1.84 to 3.53, 15 studies, 2447 women; no heterogeneity (I(2) = 0%), moderate quality evidence). The most common side effects associated with a moderate dose of SSRIs were nausea (NNH = 7), asthenia or decreased energy (NNH = 9), somnolence (NNH = 13), fatigue (NNH = 14), decreased libido (NNH = 14) and sweating (NNH = 14). In secondary analyses, SSRIs were effective for treating specific types of symptoms (that is psychological, physical and functional symptoms, and irritability). Adverse effects were dose-related.The overall quality of the evidence was low to moderate, the main weakness in the included studies being poor reporting of methods. Heterogeneity was low or absent for most outcomes, though (as noted above) there was moderate heterogeneity for one of the primary analyses.
AUTHORS' CONCLUSIONS
SSRIs are effective in reducing the symptoms of PMS, whether taken in the luteal phase only or continuously. Adverse effects are relatively frequent, the most common being nausea and asthenia. Adverse effects are dose-dependent.
Topics: Adolescent; Adult; Female; Humans; Luteal Phase; Middle Aged; Premenstrual Syndrome; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors; Young Adult
PubMed: 23744611
DOI: 10.1002/14651858.CD001396.pub3 -
Health Technology Assessment... Feb 2019Postpartum haemorrhage (PPH) is the leading cause of maternal mortality worldwide. Prophylactic uterotonic drugs can reduce blood loss and are routinely recommended....
BACKGROUND
Postpartum haemorrhage (PPH) is the leading cause of maternal mortality worldwide. Prophylactic uterotonic drugs can reduce blood loss and are routinely recommended. There are several uterotonic drugs for preventing PPH, but it is still debatable which drug or combination of drugs is the most effective.
OBJECTIVES
To identify the most effective and cost-effective uterotonic drug(s) to prevent PPH, and generate a ranking according to their effectiveness and side-effect profile.
METHODS
The Cochrane Pregnancy and Childbirth's Trials Register (1 June 2015), ClinicalTrials.gov and the World Health Organization (WHO)'s International Clinical Trials Registry Platform (ICTRP) were searched for unpublished trial reports (30 June 2015). In addition, reference lists of retrieved studies (updated October 2017) were searched for randomised trials evaluating uterotonic drugs for preventing PPH. The study estimated relative effects and rankings for preventing PPH, defined as blood loss of ≥ 500 ml and ≥ 1000 ml. Pairwise meta-analyses and network meta-analysis were performed to determine the relative effects and rankings of all available drugs and combinations thereof [ergometrine, misoprostol (Cytotec; Pfizer Inc., New York, NY, USA), misoprostol plus oxytocin (Syntocinon; Novartis International AG, Basel, Switzerland), carbetocin (Pabal; Ferring Pharmaceuticals, Saint-Prex, Switzerland), ergometrine plus oxytocin (Syntometrine; Alliance Pharma plc, Chippenham, UK), oxytocin, and a placebo or no treatment]. Primary outcomes were stratified according to the mode of birth, prior risk of PPH, health-care setting, drug dosage, regimen and route of drug administration. Sensitivity analyses were performed according to study quality and funding source, among others. A model-based economic evaluation compared the relative cost-effectiveness separately for vaginal births and caesareans with or without including side effects.
RESULTS
From 137 randomised trials and 87,466 women, ergometrine plus oxytocin, carbetocin and misoprostol plus oxytocin were found to reduce the risk of PPH blood loss of ≥ 500 ml compared with the standard drug, oxytocin [ergometrine plus oxytocin: risk ratio (RR) 0.69, 95% confidence interval (CI) 0.57 to 0.83; carbetocin: RR 0.72, 95% CI 0.52 to 1.00; misoprostol plus oxytocin: RR 0.73, 95% CI 0.6 to 0.9]. Each of these three strategies had 100% cumulative probability of being ranked first, second or third most effective. Oxytocin was ranked fourth, with an almost 0% cumulative probability of being ranked in the top three. Similar rankings were noted for the reduction of PPH blood loss of ≥ 1000 ml (ergometrine plus oxytocin: RR 0.77, 95% CI 0.61 to 0.95; carbetocin: RR 0.70, 95% CI 0.38 to 1.28; misoprostol plus oxytocin: RR 0.90, 95% CI 0.72 to 1.14), and most secondary outcomes. Ergometrine plus oxytocin and misoprostol plus oxytocin had the poorest ranking for side effects. Carbetocin had a favourable side-effect profile, which was similar to oxytocin. However, the analysis was restricted to high-quality studies, carbetocin lost its ranking and was comparable to oxytocin. The relative cost-effectiveness of the alternative strategies is inconclusive, and the results are affected by both the uncertainty and inconsistency in the data reported on adverse events. For vaginal delivery, when assuming no adverse events, ergometrine plus oxytocin is less costly and more effective than all strategies except carbetocin. The strategy of carbetocin is both more effective and more costly than all other strategies. When taking adverse events into consideration, all prevention strategies, except oxytocin, are more costly and less effective than carbetocin. For delivery by caesarean section, with and without adverse events, the relative cost-effectiveness is different, again because of the uncertainty in the available data.
LIMITATIONS
There was considerable uncertainty in findings within the planned subgroup analyses, and subgroup effects cannot be ruled out.
CONCLUSIONS
Ergometrine plus oxytocin, carbetocin and misoprostol plus oxytocin are more effective uterotonic drug strategies for preventing PPH than the current standard, oxytocin. Ergometrine plus oxytocin and misoprostol plus oxytocin cause significant side effects. Carbetocin has a favourable side-effect profile, which was similar to oxytocin. However, most carbetocin trials are small and of poor quality. There is a need for a large high-quality trial comparing carbetocin with oxytocin; such a trial is currently being conducted by the WHO. The relative cost-effectiveness is inconclusive, and results are affected by uncertainty and inconsistency in adverse events data.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42015020005; Cochrane Pregnancy and Childbirth Group (substudy) reference number 0871; PROSPERO-Cochrane (substudy) reference number CRD42015026568; and sponsor reference number ERN_13-1414 (University of Birmingham, Birmingham, UK).
FUNDING
Funding for this study was provided by the National Institute for Health Research Health Technology Assessment programme in a research award to the University of Birmingham and supported by the UK charity Ammalife (UK-registered charity 1120236). The funders of the study had no role in study design, data collection, data synthesis, interpretation or writing of the report.
Topics: Clinical Trials as Topic; Delivery, Obstetric; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Ergonovine; Female; Humans; Misoprostol; Network Meta-Analysis; Oxytocics; Oxytocin; Postpartum Hemorrhage; Pregnancy
PubMed: 30821683
DOI: 10.3310/hta23090