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The Cochrane Database of Systematic... Jan 2016Recurrent miscarriage affects 1% to 3% of women of reproductive age and mostly occurs before the 10th week of gestation (and around the same gestational week in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Recurrent miscarriage affects 1% to 3% of women of reproductive age and mostly occurs before the 10th week of gestation (and around the same gestational week in subsequent miscarriages). Although most pregnant women may not recognise a miscarriage until uterine bleeding and cramping occur, a repeat miscarriage after one or more pregnancy loss and the chance of having a successful pregnancy varies. To date, there is no universally accepted treatment for unexplained recurrent miscarriage. Chinese herbal medicines have been widely used in Asian societies for millennia and have become a popular alternative to Western medicines in recent years. Many clinical studies have reported that Chinese herbal medicines can improve pregnancy outcomes for pregnant women who had previously suffered recurrent miscarriage. This systematic review evaluated the efficacy of Chinese herbal medicines for recurrent miscarriage.
OBJECTIVES
To assess the effectiveness and safety of Chinese herbal medicines for the treatment of unexplained recurrent miscarriage.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (01 June 2015), Embase (1980 to 01 June 2015); Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to 01 June 2015); Chinese Biomedical Database (CBM) (1978 to 01 June 2015); China Journal Net (CJN) (1915 to 01 June 2015); China Journals Full-text Database (1915 to 01 June 2015); and WanFang Database (Chinese Ministry of Science & Technology) (1980 to 01 June 2015). We also searched reference lists of relevant trials and reviews. We identified and contacted organisations, individual experts working in the field, and medicinal herb manufacturers.
SELECTION CRITERIA
Randomised or quasi-randomised controlled trials, including cluster-randomised trials, with or without full text, comparing Chinese herbal medicines (alone or combined with other intervention or other pharmaceuticals) with placebo, no treatment, other intervention (including bed rest and psychological support), or other pharmaceuticals as treatments for unexplained recurrent miscarriage. Cross-over studies were not eligible for inclusion in this review.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed all the studies for inclusion in the review, assessed risk of bias and extracted the data. Data were checked for accuracy.
MAIN RESULTS
We included nine randomised clinical trials (involving 861 women). The trials compared Chinese herbal medicines (various formulations) either alone (one trial), or in combination with other pharmaceuticals (seven trials) versus other pharmaceuticals alone. One study compared Chinese herbal medicines and other pharmaceuticals versus psychotherapy. We did not identify any trials comparing Chinese herbal medicines with placebo or no treatment, including bed rest.Various Chinese herbal medicines were used in the different trials (and some of the classical the formulations were modified in the trials). The Western pharmaceutical medicines included tocolytic drugs such as salbutamol and magnesium sulphate; hormonal supplementation with human chorionic gonadotrophin (HCG), progesterone or dydrogesterone; and supportive supplements such as vitamin E, vitamin K and folic acid.Overall, the methodological quality of the included studies was poor with unclear risk of bias for nearly all the 'Risk of bias' domains assessed.Chinese herbal medicines alone versus other pharmaceuticals alone - the live birth rate was no different between the two groups (risk ratio (RR) 1.05; 95% confidence interval (CI) 0.67 to 1.65; one trial, 80 women). No data were available for the outcome of pregnancy rate (continuation of pregnancy after 20 weeks of gestation).In contrast, the continuing pregnancy rate (RR 1.27 95% CI 1.10 to 1.48, two trials, 189 women) and live birth rate (average RR 1.55; 95% CI 1.14 to 2.10; six trials, 601 women, Tau² = 0.10; I² = 73%) were higher among the group of women who received a combination of Chinese herbal medicines and other pharmaceuticals when compared with women who received other pharmaceuticals alone.For Chinese herbal medicines and psychotherapy versus psychotherapy alone (one study) - there was a higher live birth rate (RR 1.32; 95% CI 1.07 to 1.64; one trial, 90 women) in the group of women who received a combination of Chinese herbal medicines and psychotherapy compared to those women who received psychotherapy alone. No data were available on the continuing pregnancy rate for this comparison.Other primary outcomes (maternal adverse effect and toxicity rate and the perinatal adverse effect and toxicity rate) were not reported in most of the included studies. Two trials (341 women) reported that no maternal adverse effects were found (one trial compared (combined) medicines with other pharmaceuticals, and one trial compared combined Chinese herbal medicine alone versus other pharmaceuticals). One trial (Chinese herbal medicine alone versus other pharmaceuticals alone) reported that there were no abnormal fetuses (ultrasound) or after delivery.There were no data reported for any of this review's secondary outcomes.
AUTHORS' CONCLUSIONS
We found limited evidence (from nine studies with small sample sizes and unclear risk of bias) to assess the effectiveness of Chinese herbal medicines for treating unexplained recurrent miscarriage; no data were available to assess the safety of the intervention for the mother or her baby. There were no data relating to any of this review's secondary outcomes. From the limited data we found, a combination of Chinese herbal medicines and other pharmaceuticals (mainly Western medicines) may be more effective than Western medicines alone in terms of the rate of continuing pregnancy and the rate of live births. However, the methodological quality of the included studies was generally poor.A comparison of Chinese herbal medicines alone versus placebo or no treatment (including bed rest) was not possible as no relevant trials were identified.More high-quality studies are needed to further evaluate the effectiveness and safety of Chinese herbal medicines for unexplained recurrent miscarriage. In addition to assessing the effect of Chinese herbal medicines on pregnancy rate and the rate of live births, future studies should also consider safety issues (adverse effects and toxicity for the mother and her baby) as well as the secondary outcomes listed in this review. This review would provide more valuable information if the included studies could overcome the problems in their designs, such as lacking of qualified placebo-controlled trials, applying adequate randomisation methods and avoiding potential bias.
Topics: Abortion, Habitual; Adult; Birth Rate; Drugs, Chinese Herbal; Female; Hormones; Humans; Live Birth; Pregnancy; Pregnancy Rate; Psychotherapy; Randomized Controlled Trials as Topic; Tocolytic Agents
PubMed: 26760986
DOI: 10.1002/14651858.CD010568.pub2 -
The Cochrane Database of Systematic... Aug 2014Magnesium sulphate has been used in some settings as a tocolytic agent to inhibit uterine activity in women in preterm labour with the aim of preventing preterm birth. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Magnesium sulphate has been used in some settings as a tocolytic agent to inhibit uterine activity in women in preterm labour with the aim of preventing preterm birth.
OBJECTIVES
To assess the effects of magnesium sulphate therapy given to women in threatened preterm labour with the aim of preventing preterm birth and its sequelae.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (last searched 31 January 2014).
SELECTION CRITERIA
Randomised controlled trials of magnesium sulphate as the only tocolytic, administered by any route, compared with either placebo, no treatment or alternative tocolytic therapy (not magnesium sulphate) to women considered to be in preterm labour.
DATA COLLECTION AND ANALYSIS
At least two review authors assessed trial eligibility and risk of bias and undertook data extraction independently.
MAIN RESULTS
The 37 included trials (total of 3571 women and over 3600 babies) were generally of moderate to high risk of bias. Antenatal magnesium sulphate was compared with either placebo, no treatment, or a range of alternative tocolytic agents.For the primary outcome of giving birth within 48 hours after trial entry, no significant differences were seen between women who received magnesium sulphate and women who did not (whether placebo/no alternative tocolytic drug, betamimetics, calcium channel blockers, cox inhibitors, prostaglandin inhibitors, or human chorionic gonadotropin) (19 trials, 1913 women). Similarly for the primary outcome of serious infant outcome, there were no significant differences between the infants exposed to magnesium sulphate and those not (whether placebo/no alternative tocolytic drug, betamimetics, calcium channel blockers, cox inhibitors, prostaglandin inhibitors, human chorionic gonadotropin or various tocolytic drugs) (18 trials; 2187 babies). No trials reported the outcome of extremely preterm birth. In the seven trials that reported serious maternal outcomes, no events were recorded.In the group treated with magnesium sulphate compared with women receiving antenatal placebo or no alternative tocolytic drug, a borderline increased risk of total death (fetal, neonatal, infant) was seen (risk ratio (RR) 4.56, 95% confidence interval (CI) 1.00 to 20.86; two trials, 257 babies); none of the comparisons between magnesium sulphate and other classes of tocolytic drugs showed differences for this outcome (10 trials, 991 babies). The outcomes of neonatal and/or infant deaths and of fetal deaths did not show differences between magnesium sulphate and no magnesium sulphate, whether compared with placebo/no alternative tocolytic drug, or any specific class of tocolytic drug. For most of the other secondary outcomes, there were no significant differences between magnesium sulphate and the control groups for risk of preterm birth (except for a significantly lower risk with magnesium sulphate when compared with barbiturates in one trial of 65 women), gestational age at birth, interval between trial entry and birth, other neonatal morbidities, or neurodevelopmental outcomes. Duration of neonatal intensive care unit stay was significantly increased in the magnesium sulphate group compared with the calcium channel blocker group, but not when compared with cox inhibitors or prostaglandin inhibitors. No maternal deaths were reported in the four trials reporting this outcome. Significant differences between magnesium sulphate and controls were not seen for maternal adverse events severe enough to stop treatment, except for a significant benefit of magnesium sulphate compared with betamimetics in a single trial.
AUTHORS' CONCLUSIONS
Magnesium sulphate is ineffective at delaying birth or preventing preterm birth, has no apparent advantages for a range of neonatal and maternal outcomes as a tocolytic agent and its use for this indication may be associated with an increased risk of total fetal, neonatal or infant mortality (in contrast to its use in appropriate groups of women for maternal, fetal, neonatal and infant neuroprotection where beneficial effects have been demonstrated).
Topics: Female; Fetal Death; Humans; Magnesium Sulfate; Obstetric Labor, Premature; Pregnancy; Premature Birth; Randomized Controlled Trials as Topic; Tocolytic Agents; Treatment Outcome
PubMed: 25126773
DOI: 10.1002/14651858.CD001060.pub2 -
The Cochrane Database of Systematic... Aug 2015Head injury is a common event and can cause a spectrum of motor and cognition disabilities. A frequent complication is seizures. Antiepileptic drugs (AED) such as... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Head injury is a common event and can cause a spectrum of motor and cognition disabilities. A frequent complication is seizures. Antiepileptic drugs (AED) such as phenytoin are often used in clinical practice with the hopes of preventing post-traumatic epilepsy. Whether immediate medical intervention following head trauma with either AEDs or neuroprotective drugs can alter the process of epileptogenesis and lead to a more favorable outcome is currently unknown. This review attempted to address the effectiveness of these treatment interventions. This review updates and expands on the earlier Cochrane review.
OBJECTIVES
To compare the efficacy of antiepileptic drugs and neuroprotective agents with placebo, usual care or other pharmacologic agents for the prevention of post-traumatic epilepsy in people diagnosed with any severity of traumatic brain injury.
SEARCH METHODS
We searched The Cochrane Epilepsy Group's specialized register, CENTRAL, MEDLINE, ClinicalTrials.gov and World Health Organization International Clinical Trials Registry Platform (ICTRP) in January 2015. We searched EMBASE, Biological Abstracts and National Research Register in September 2014 and SCOPUS in December 2013. The Cochrane Epilepsy Group performed handsearches of relevant journals.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) that include AEDs or neuroprotective agents compared with placebo, another pharmacologic agent or a usual care group. The outcomes measured included a seizure occurring within one week of trauma (early seizure), seizure occurring later than one week post-trauma (late seizure), mortality and any adverse events.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed study quality and extracted the data. We calculated risk ratios (RR) and 95% confidence intervals (CI) for each outcome. We used random-effects models in the meta-analyses and performed pre-defined subgroup and sensitivity analyses.
MAIN RESULTS
This review included 10 RCTs (reported in 12 articles) consisting of 2326 participants The methodological quality of the studies varied. The type of intervention was separated into three categories; AED versus placebo or standard care, alternative neuroprotective agent versus placebo or standard care and AED versus other AED. Treatment with an AED (phenytoin or carbamazepine) decreased the risk of early seizure compared with placebo or standard care (RR 0.42, 95% CI 0.23 to 0.73; very low quality evidence). There was no evidence of a difference in the risk of late seizure occurrence between AEDs and placebo or standard care (RR 0.91, 95% CI 0.57 to 1.46; very low quality evidence). There was no evidence of a significant difference in all-cause mortality between AEDs and placebo or standard care (RR 1.08 95% CI 0.79 to 1.46,very low quality of evidence). Only one study looked at other potentially neuroprotective agents (magnesium sulfate) compared with placebo. The risk ratios were: late seizure 1.07 (95% CI 0.53 to 2.17) and all-cause mortality 1.20 (95% CI 0.80 to 1.81). The risk ratio for occurrence of early seizure was not estimable.Two studies looked at comparison of two AEDs (levetiracetam, valproate) with phenytoin used as the main comparator in each study. The risk ratio for all-cause mortality was 0.53 (95% CI 0.30 to 0.94). There was no evidence of treatment benefit of phenytoin compared with another AED for early seizures (RR 0.66, 95% 0.20 to 2.12) or late seizures(RR 0.77, 95% CI 0.46 to 1.30).Only two studies reported adverse events. The RR of any adverse event with AED compared with placebo was 1.65 (95% CI 0.73 to 3.66; low quality evidence). There were insufficient data on adverse events in the other treatment comparisons.
AUTHORS' CONCLUSIONS
This review found low-quality evidence that early treatment with an AED compared with placebo or standard care reduced the risk of early post-traumatic seizures. There was no evidence to support a reduction in the risk of late seizures or mortality. There was insufficient evidence to make any conclusions regarding the effectiveness or safety of other neuroprotective agents compared with placebo or for the comparison of phenytoin, a traditional AED, with another AED.
Topics: Adult; Anticonvulsants; Carbamazepine; Cause of Death; Child; Craniocerebral Trauma; Epilepsy; Humans; Levetiracetam; Magnesium Sulfate; Neuroprotective Agents; Phenytoin; Piracetam; Randomized Controlled Trials as Topic; Valproic Acid
PubMed: 26259048
DOI: 10.1002/14651858.CD009900.pub2 -
Journal of Caring Sciences Mar 2020Primary dysmenorrhea is considered as one of the main problems in women. This review study aimed to characterize the effect of micronutrients on primary dysmenorrhea.... (Review)
Review
Primary dysmenorrhea is considered as one of the main problems in women. This review study aimed to characterize the effect of micronutrients on primary dysmenorrhea. In this systematic and meta-analysis study, the articles were searched at Cochrane library, PubMed, Scopus, Web of Science databases. The searching process was conducted with the key terms related to dysmenorrhea and micronutrients. Risk of bias assessment was performed, using Rev Man 5.3 software. In view of the heterogeneity of some of the studies, they were analyzed, using a qualitative method (n=10), and only 6 studies were included in Meta analyze. STATA statistical software version 11 was used for the analysis. In this study, finally 16 clinical trials were investigated. Most micronutrients studied in the relevant articles had anti-inflammatory and analgesic properties with a desirable effect on dysmenorrhea pain relief. Vitamins (K, D, B1, and E) and calcium, magnesium, zinc sulfate and boron contributed effectively to dysmenorrhea pain management. Two months after the intervention, there was a significant mean decrease in the pain score for the vitamin D intervention group (SMD: -1.02, 95% CI: -1.9 to - 0.14, P =0.024) , as well as in the vitamin E intervention group compared to placebo group (SMD: -0.47,95% CI:-0.74 to - 0.2, P = 0.001). Despite the paucity of related research, the studies indicated the potential effects of micronutrients on reducing the pain severity in primary dysmenorrhea. But more studies are needed to confirm the safety and effectiveness of various types of micronutrients on primary dysmenorrhea.
PubMed: 32296659
DOI: 10.34172/jcs.2020.008 -
The Cochrane Database of Systematic... May 2024Magnesium sulphate is a common therapy in perinatal care. Its benefits when given to women at risk of preterm birth for fetal neuroprotection (prevention of cerebral... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Magnesium sulphate is a common therapy in perinatal care. Its benefits when given to women at risk of preterm birth for fetal neuroprotection (prevention of cerebral palsy for children) were shown in a 2009 Cochrane review. Internationally, use of magnesium sulphate for preterm cerebral palsy prevention is now recommended practice. As new randomised controlled trials (RCTs) and longer-term follow-up of prior RCTs have since been conducted, this review updates the previously published version.
OBJECTIVES
To assess the effectiveness and safety of magnesium sulphate as a fetal neuroprotective agent when given to women considered to be at risk of preterm birth.
SEARCH METHODS
We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) on 17 March 2023, as well as reference lists of retrieved studies.
SELECTION CRITERIA
We included RCTs and cluster-RCTs of women at risk of preterm birth that assessed prenatal magnesium sulphate for fetal neuroprotection compared with placebo or no treatment. All methods of administration (intravenous, intramuscular, and oral) were eligible. We did not include studies where magnesium sulphate was used with the primary aim of preterm labour tocolysis, or the prevention and/or treatment of eclampsia.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed RCTs for inclusion, extracted data, and assessed risk of bias and trustworthiness. Dichotomous data were presented as summary risk ratios (RR) with 95% confidence intervals (CI), and continuous data were presented as mean differences with 95% CI. We assessed the certainty of the evidence using the GRADE approach.
MAIN RESULTS
We included six RCTs (5917 women and their 6759 fetuses alive at randomisation). All RCTs were conducted in high-income countries. The RCTs compared magnesium sulphate with placebo in women at risk of preterm birth at less than 34 weeks' gestation; however, treatment regimens and inclusion/exclusion criteria varied. Though the RCTs were at an overall low risk of bias, the certainty of evidence ranged from high to very low, due to concerns regarding study limitations, imprecision, and inconsistency. Primary outcomes for infants/children: Up to two years' corrected age, magnesium sulphate compared with placebo reduced cerebral palsy (RR 0.71, 95% CI 0.57 to 0.89; 6 RCTs, 6107 children; number needed to treat for additional beneficial outcome (NNTB) 60, 95% CI 41 to 158) and death or cerebral palsy (RR 0.87, 95% CI 0.77 to 0.98; 6 RCTs, 6481 children; NNTB 56, 95% CI 32 to 363) (both high-certainty evidence). Magnesium sulphate probably resulted in little to no difference in death (fetal, neonatal, or later) (RR 0.96, 95% CI 0.82 to 1.13; 6 RCTs, 6759 children); major neurodevelopmental disability (RR 1.09, 95% CI 0.83 to 1.44; 1 RCT, 987 children); or death or major neurodevelopmental disability (RR 0.95, 95% CI 0.85 to 1.07; 3 RCTs, 4279 children) (all moderate-certainty evidence). At early school age, magnesium sulphate may have resulted in little to no difference in death (fetal, neonatal, or later) (RR 0.82, 95% CI 0.66 to 1.02; 2 RCTs, 1758 children); cerebral palsy (RR 0.99, 95% CI 0.69 to 1.41; 2 RCTs, 1038 children); death or cerebral palsy (RR 0.90, 95% CI 0.67 to 1.20; 1 RCT, 503 children); and death or major neurodevelopmental disability (RR 0.81, 95% CI 0.59 to 1.12; 1 RCT, 503 children) (all low-certainty evidence). Magnesium sulphate may also have resulted in little to no difference in major neurodevelopmental disability, but the evidence is very uncertain (average RR 0.92, 95% CI 0.53 to 1.62; 2 RCTs, 940 children; very low-certainty evidence). Secondary outcomes for infants/children: Magnesium sulphate probably reduced severe intraventricular haemorrhage (grade 3 or 4) (RR 0.76, 95% CI 0.60 to 0.98; 5 RCTs, 5885 infants; NNTB 92, 95% CI 55 to 1102; moderate-certainty evidence) and may have resulted in little to no difference in chronic lung disease/bronchopulmonary dysplasia (average RR 0.92, 95% CI 0.77 to 1.10; 5 RCTs, 6689 infants; low-certainty evidence). Primary outcomes for women: Magnesium sulphate may have resulted in little or no difference in severe maternal outcomes potentially related to treatment (death, cardiac arrest, respiratory arrest) (RR 0.32, 95% CI 0.01 to 7.92; 4 RCTs, 5300 women; low-certainty evidence). However, magnesium sulphate probably increased maternal adverse effects severe enough to stop treatment (average RR 3.21, 95% CI 1.88 to 5.48; 3 RCTs, 4736 women; moderate-certainty evidence). Secondary outcomes for women: Magnesium sulphate probably resulted in little to no difference in caesarean section (RR 0.96, 95% CI 0.91 to 1.02; 5 RCTs, 5861 women) and postpartum haemorrhage (RR 0.94, 95% CI 0.80 to 1.09; 2 RCTs, 2495 women) (both moderate-certainty evidence). Breastfeeding at hospital discharge and women's views of treatment were not reported.
AUTHORS' CONCLUSIONS
The currently available evidence indicates that magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus, compared with placebo, reduces cerebral palsy, and death or cerebral palsy, in children up to two years' corrected age, and probably reduces severe intraventricular haemorrhage for infants. Magnesium sulphate may result in little to no difference in outcomes in children at school age. While magnesium sulphate may result in little to no difference in severe maternal outcomes (death, cardiac arrest, respiratory arrest), it probably increases maternal adverse effects severe enough to stop treatment. Further research is needed on the longer-term benefits and harms for children, into adolescence and adulthood. Additional studies to determine variation in effects by characteristics of women treated and magnesium sulphate regimens used, along with the generalisability of findings to low- and middle-income countries, should be considered.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Bias; Cerebral Palsy; Magnesium Sulfate; Neuroprotective Agents; Premature Birth; Randomized Controlled Trials as Topic; Tocolytic Agents
PubMed: 38726883
DOI: 10.1002/14651858.CD004661.pub4 -
The Cochrane Database of Systematic... Oct 2014Asthma is the most common respiratory disorder complicating pregnancy, and is associated with a range of adverse maternal and perinatal outcomes. There is strong... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Asthma is the most common respiratory disorder complicating pregnancy, and is associated with a range of adverse maternal and perinatal outcomes. There is strong evidence however, that the adequate control of asthma can improve health outcomes for mothers and their babies. Despite known risks of poorly controlled asthma during pregnancy, a large proportion of women have sub-optimal asthma control, due to concerns surrounding risks of pharmacological agents, and uncertainties regarding the effectiveness and safety of different management strategies.
OBJECTIVES
To assess the effects of interventions (pharmacologic and non-pharmacologic) for managing women's asthma in pregnancy on maternal and fetal/infant outcomes.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (2 June 2014) and the Cochrane Airways Group's Trials Register (4 June 2014).
SELECTION CRITERIA
Randomised and quasi-randomised controlled trials comparing any intervention used to manage asthma in pregnancy, with placebo, no intervention, or an alternative intervention. We included pharmacological and non-pharmacological interventions (including combined interventions). Cluster-randomised trials were eligible for inclusion (but none were identified). Cross-over trials were not eligible for inclusion.We included multi-armed trials along with two-armed trials. We also included studies published as abstracts only.
DATA COLLECTION AND ANALYSIS
At least two review authors independently assessed trial eligibility and quality and extracted data. Data were checked for accuracy.
MAIN RESULTS
We included eight trials in this review, involving 1181 women and their babies. Overall we judged two trials to be at low risk of bias, two to be of unclear risk of bias, and four to be at moderate risk of bias.Five trials assessed pharmacological agents, including inhaled corticosteroids (beclomethasone or budesonide), inhaled magnesium sulphate, intravenous theophylline, and inhaled beclomethasone verus oral theophylline. Three trials assessed non-pharmacological interventions, including a fractional exhaled nitric oxide (FENO)-based algorithm versus a clinical guideline-based algorithm to adjust inhaled corticosteroid therapy, a pharmacist-led multi-disciplinary approach to management versus standard care, and progressive muscle relaxation (PMR) versus sham training.The eight included trials were assessed under seven separate comparisons. Pharmacological interventionsPrimary outcomes: one trial suggested that inhaled magnesium sulphate in addition to usual treatment could reduce exacerbation frequency in acute asthma (mean difference (MD) -2.80; 95% confidence interval (CI) -3.21 to -2.39; 60 women). One trial assessing the addition of intravenous theophylline to standard care in acute asthma did not report on exacerbations (65 women). No clear difference was shown in the risk of exacerbations with the use of inhaled beclomethasone in addition to usual treatment for maintenance therapy in one trial (risk ratio (RR) 0.36; 95% CI 0.13 to 1.05; 60 women); a second trial also showed no difference, however data were not clearly reported to allow inclusion in a meta-analysis. No difference was shown when inhaled beclomethasone was compared with oral theophylline for maintenance therapy (RR 0.88; 95% CI 0.59 to 1.33; one trial, 385 women). None of these trials reported on neonatal intensive care admissions.
SECONDARY OUTCOMES
inhaled magnesium sulphate in acute asthma was shown to improve lung function measures (one trial, 60 women); intravenous theophylline in acute asthma was not associated with benefits (one trial, 65 women). No clear differences were seen with the addition of inhaled corticosteroids to routine treatment in three trials (374 women). While inhaled beclomethasone, compared with oral theophylline, significantly reduced treatment discontinuation due to adverse effects in one trial (384 women), no other differences were observed, except for higher treatment adherence with theophylline. Four of the five trials did not report on adverse effects. Non-pharmacological interventionsPrimary outcomes: in one trial, the use of a FENO-based algorithm was shown to significantly reduce asthma exacerbations (RR 0.61; 95% CI 0.41 to 0.90; 220 women); and a trend towards fewer neonatal hospitalisations was observed (RR 0.46; 95% CI 0.21 to 1.02; 214 infants). No exacerbations occurred in one trial assessing pharmacist-led management; this approach did not reduce neonatal intensive care admissions (RR 1.50; 95% CI 0.27 to 8.32; 58 infants). One trial (64 women) assessing PMR did not report on exacerbations or neonatal intensive care admissions.
SECONDARY OUTCOMES
the use of a FENO-based algorithm to adjust therapy led to some improvements in quality of life scores, as well as more frequent use of inhaled corticosteroids and long-acting β-agonists, and less frequent use of short-acting β-agonists (one trial, 220 women). The FENO-based algorithm was associated with fewer infants with recurrent episodes of bronchiolitis in their first year of life, and a trend towards fewer episodes of croup for infants. Pharmacist-led management improved asthma control scores at six months (one trial, 60 women); PMR improved lung function and quality of life measures (one trial, 64 women). No other differences between comparisons were observed.
AUTHORS' CONCLUSIONS
Based on eight included trials, of moderate quality overall, no firm conclusions about optimal interventions for managing asthma in pregnancy can be made. Five trials assessing pharmacological interventions did not provide clear evidence of benefits or harms to support or refute current practice. While inhaled magnesium sulphate for acute asthma was shown to reduce exacerbations, this was in one small trial of unclear quality, and thus this finding should be interpreted with caution. Three trials assessing non-pharmacological interventions provided some support for the use of such strategies, however were not powered to detect differences in important maternal and infant outcomes. While a FENO-based algorithm reduced exacerbations, the effects on perinatal outcomes were less certain, and thus widespread implementation is not yet appropriate. Similarly, though positive effects on asthma control were shown with PMR and pharmacist-led management, the evidence to date is insufficient to draw definitive conclusions.In view of the limited evidence base, further randomised trials are required to determine the most effective and safe interventions for asthma in pregnancy. Future trials must be sufficiently powered, and well-designed, to allow differences in important outcomes for mothers and babies to be detected. The impact on health services requires evaluation. Any further trials assessing pharmacological interventions should assess novel agents or those used in current practice. Encouragingly, at least five trials have been identified as planned or underway.
Topics: Adrenal Cortex Hormones; Algorithms; Anti-Asthmatic Agents; Asthma; Beclomethasone; Female; Humans; Magnesium Sulfate; Muscle Relaxation; Nitric Oxide; Pregnancy; Pregnancy Complications; Randomized Controlled Trials as Topic; Theophylline
PubMed: 25331331
DOI: 10.1002/14651858.CD010660.pub2 -
The Cochrane Database of Systematic... Jul 2014Preterm birth represents the single largest cause of mortality and morbidity for newborns and a major cause of morbidity for pregnant women. Tocolytic agents include a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Preterm birth represents the single largest cause of mortality and morbidity for newborns and a major cause of morbidity for pregnant women. Tocolytic agents include a wide range of drugs that can inhibit labour to prolong pregnancy. This may gain time to allow the fetus to mature further before being born, permit antenatal corticosteroid administration for lung maturation, and allow time for intra-uterine transfer to a hospital with neonatal intensive care facilities. However, some tocolytic drugs are associated with severe side effects. Combinations of tocolytic drugs may be more effective over single tocolytic agents or no intervention, without adversely affecting the mother or neonate.
OBJECTIVES
To assess the effects on maternal, fetal and neonatal outcomes of any combination of tocolytic drugs for the treatment of preterm labour when compared with any other treatment, no treatment or placebo.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 January 2014) and reference lists of retrieved studies.
SELECTION CRITERIA
We included randomised controlled trials comparing a combination of tocolytic agents, administered by any route or any dose, for inhibiting preterm labour versus any other treatment (including other combinations of tocolytics or single tocolytics), no intervention or placebo.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed study reports for eligibility, carried out data extraction and assessed risk of bias.
MAIN RESULTS
Eleven studies met our inclusion criteria. Two studies did not report any outcome data relevant to the review, so the results of the review are based on nine trials that contributed data. Primary outcomes were perinatal mortality, serious maternal or infant outcomes, adverse drug reactions, birth before 48 hours of trial entry, birth before 34 weeks' gestation and preterm neonates delivered without a full course of antenatal steroids completed 24 hours before birth. The quality of evidence in included trials was mixed; only three of the trials were placebo controlled.The included trials examined seven different comparisons: intravenous (IV) ritodrine plus oral or IV magnesium (sulphate or gluconate) versus IV ritodrine alone (three trials, 231 women); IV ritodrine plus indomethacin suppositories versus IV ritodrine alone (one trial, 208 women); IV ritodrine plus vaginal progesterone versus IV ritodrine alone (one trial, 83 women); IV hexoprenaline sulphate plus IV magnesium hydrochloride versus IV hexoprenaline sulphate alone (one trial, 24 women); IV fenoterol plus oral naproxen versus IV fenoterol alone (one trial, 72 women); oral pentoxifylline plus IV magnesium sulphate plus IV fenoterol versus IV magnesium sulphate plus IV fenoterol (one trial, 125 women); and, IV terbutaline plus oral metoprolol versus IV terbutaline alone (one trial, 17 women). Few studies with small numbers of women were available for each comparison, hence very little data were pooled in meta-analysis. In all trials, not many of the primary outcomes were reported.Three trials examined intravenous (IV) ritodrine plus IV or oral magnesium (sulphate or gluconate) compared with IV ritodrine alone. One study, with 41 women, reported more adverse drug reactions in the group receiving the combined tocolytics (risk ratio (RR) 7.79, 95% confidence interval (CI) 1.11 to 54.80). Two trials reported discontinuation of therapy due to severe side effects (results were not combined due to high statistical heterogeneity, I² = 83%); one trial reported increased severe side effects in the group receiving IV ritodrine alone (RR 7.79, 95% CI 1.11 to 54.80, 41 women); in the other trial there was no clear difference between groups (RR 0.23, 95% CI 0.03 to 1.97, 107 women). Other primary outcomes were not reported.One trial assessed IV ritodrine plus indomethacin suppositories versus IV ritodrine alone. There were no significant differences between groups for perinatal mortality or serious neonatal morbidity. Results for other primary outcomes were not reported.There were no significant differences between groups receiving IV ritodrine plus vaginal progesterone compared with IV ritodrine alone for most outcomes reported, although the latency period (time from recruitment to delivery) was increased in the group receiving the combination of tocolytics.For other combinations of tocolytic agents, primary outcomes were rarely reported and for secondary outcomes results did not demonstrate differences between groups.
AUTHORS' CONCLUSIONS
It is unclear whether a combination of tocolytic drugs for preterm labour is more advantageous for women and/or newborns due to a lack of large, well-designed trials including the outcomes of interest. There are no trials of combination regimens using widely used tocolytic agents, such as calcium channel blockers (nifedipine) and/or oxytocin receptor antagonists (atosiban). Further trials are needed before specific conclusions on use of combination tocolytic therapy for preterm labour can be made.
Topics: Drug Therapy, Combination; Female; Humans; Infant, Newborn; Obstetric Labor, Premature; Pregnancy; Premature Birth; Randomized Controlled Trials as Topic; Tocolysis; Tocolytic Agents
PubMed: 25010869
DOI: 10.1002/14651858.CD006169.pub2 -
The Cochrane Database of Systematic... Sep 2019Sickle cell disease is an autosomal recessive inherited haemoglobinopathy which causes painful vaso-occlusive crises due to sickle red blood cell dehydration....
BACKGROUND
Sickle cell disease is an autosomal recessive inherited haemoglobinopathy which causes painful vaso-occlusive crises due to sickle red blood cell dehydration. Vaso-occlusive crises are common painful events responsible for a variety of clinical complications; overall mortality is increased and life expectancy decreased compared to the general population. Experimental studies suggest that intravenous magnesium has proven to be well-tolerated in individuals hospitalised for the immediate relief of acute (sudden onset) painful crisis and has the potential to decrease the length of hospital stay. Some in vitro studies and open studies of long-term oral magnesium showed promising effect on pain relief but failed to show its efficacy. The studies show that oral magnesium therapy may prevent sickle red blood cell dehydration and prevent recurrent painful episodes. There is a need to access evidence for the impact of oral and intravenous magnesium effect on frequency of pain, length of hospital stay and quality of life. This is an updated version of the review.
OBJECTIVES
To evaluate the effects of short-term intravenous magnesium on the length of hospital stay and quality of life in children and adults with sickle cell disease. To determine the effects of long-term oral magnesium therapy on the frequency of painful crises and the quality of life in children and adults with sickle cell disease.
SEARCH METHODS
We searched the Cochrane Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books.Date of last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register: 03 February 2019.Date of last search of other resources (clinical trials registries): 04 April 2019.
SELECTION CRITERIA
We searched for published and unpublished randomized controlled studies of oral or intravenous magnesium compared to placebo or no magnesium.
DATA COLLECTION AND ANALYSIS
Authors independently assessed the study quality and extracted the data using standard Cochrane methodologies.
MAIN RESULTS
We included five randomized placebo-controlled studies with a total of 386 participants (aged three to 53 years). Of these, two shorter parallel studies (n = 306) compared intravenous magnesium sulphate to placebo (normal saline) for admission to hospital due to a vaso-occlusive crisis, for which we were able to analyse data. The quality of evidence was moderate for studies in this comparison, mainly due to limitations due to risk of bias and imprecision. Two of the three longer-term studies comparing oral magnesium pidolate to placebo had a cross-over design. The third was a parallel factorial study which compared hydroxyurea and oral magnesium to each other and to placebo over a longer period of time; we only present the comparison of oral magnesium to placebo from this study. The quality of evidence was very low with uncertainty of the estimation.The eight-hourly dose levels in the two studies of intravenous magnesium were different; one used 100 mg/kg while the second used 40 mg/kg. Only one of these studies (n = 104) reported the mean daily pain score while hospitalised (a non-significant difference between groups, moderate quality evidence). The second study (n = 202) reported a number of child- and parent-reported quality of life scores. None of the scores showed any difference between treatment groups (low quality evidence). Data from one study (n = 106) showed no difference in length of stay in hospital between groups (low quality evidence). Both studies reported on adverse events, but not defined by severity as we had planned. One study showed significantly more participants receiving intravenous magnesium experienced warmth at infusion site compared to placebo; there were no differences between groups for other adverse events (low quality evidence).Three studies (n = 80) compared oral magnesium pidolate to placebo. None of them reported data which we were able to analyse. One study (n = 24) reported on the number of painful days and stated there was no difference between two groups (low quality evidence). None of the studies reported on quality of life or length of hospital stay. Two studies (n = 68) reported there were no differences in levels of magnesium in either plasma or red blood cells (moderate quality evidence). Two studies (n = 56) reported adverse events. One reported episodes of mild diarrhoea and headache, all of which resolved without stopping treatment. The second study reported adverse events as gastrointestinal disorders, headache or migraine, upper respiratory infections and rash; which were all evenly distributed across treatment groups (moderate quality evidence).
AUTHORS' CONCLUSIONS
Moderate to low quality evidence showed neither intravenous magnesium and oral magnesium therapy has an effect on reducing painful crisis, length of hospital stay and changing quality of life in treating sickle cell disease. Therefore, no definitive conclusions can be made regarding its clinical benefit. Further randomized controlled studies, perhaps multicentre, are necessary to establish whether intravenous and oral magnesium therapies have any effect on improving the health of people with sickle cell disease.
Topics: Adolescent; Adult; Anemia, Sickle Cell; Antisickling Agents; Child; Child, Preschool; Female; Humans; Hydroxyurea; Magnesium; Magnesium Sulfate; Male; Middle Aged; Randomized Controlled Trials as Topic; Young Adult
PubMed: 31498421
DOI: 10.1002/14651858.CD011358.pub3 -
Journal of Pain Research 2018An updated systematic review and meta-analysis was conducted to assess the effect of prophylactic dexamethasone for tracheal intubation of general anesthesia on... (Review)
Review
BACKGROUND/AIMS
An updated systematic review and meta-analysis was conducted to assess the effect of prophylactic dexamethasone for tracheal intubation of general anesthesia on postoperative sore throat (POST).
METHODS
Comprehensive literature search of databases for randomized controlled trials (RCTs), including Embase, PubMed, and Cochrane Library, which evaluate the effect of prophylactic dexamethasone on POST was conducted. RevMan 5.0 and STATA 12.0 software were used to perform meta-analyses.
RESULTS
Fourteen RCTs totaling 1,837 patients were included for analysis. Compared with placebo, a significant reduction in the incidence of POST (OR 0.44, 95% CI 0.33-0.58, <0.00001), hoarseness (OR 0.42, 95% CI 0.31-0.58, <0.00001), and postoperative nausea and vomiting (PONV) (OR 0.06, 95% CI 0.03-0.14, <0.00001) and a comparable incidence of cough (OR 0.59, 95% CI 0.19-1.89, =0.38) was described in patients receiving dexamethasone, with or without concomitant drugs. Dexamethasone ≥0.2 mg/kg had a statistically greater impact on reducing the incidence of POST than dexamethasone 0.1-0.2 mg/kg, while dexamethasone ≤0.1 mg/kg did not. Dexamethasone was as effective as other drugs such as ondansetron, magnesium sulfate, ketamine gargle, betamethasone gel, and ketorolac for reducing POST (OR 0.70, 95% CI 0.46-1.07, =0.10). Dexamethasone plus a different drug was more effective than dexamethasone alone for reducing the incidence of POST at 24 hours (OR 0.40, 95% CI 0.21-0.77, =0.006). Compared with controls, a statistically higher blood glucose level was the only adverse event during the immediate postoperative period in patients receiving dexamethasone.
CONCLUSIONS
Intravenous dexamethasone ≥0.2 mg/kg within 30 minutes before or after induction of general anesthesia should be recommended as grade 1A evidence with safety and efficacy in reducing the incidence of POST, hoarseness, and PONV in patients without pregnancy, diabetes mellitus, or contraindications for corticosteroids.
PubMed: 30425559
DOI: 10.2147/JPR.S172419