-
Systematic Reviews Oct 2023Since 1997, several meta-analyses (MAs) of placebo-controlled randomised efficacy trials of homoeopathy for any indication (PRETHAIs) have been published with different...
BACKGROUND AND OBJECTIVE
Since 1997, several meta-analyses (MAs) of placebo-controlled randomised efficacy trials of homoeopathy for any indication (PRETHAIs) have been published with different methods, results and conclusions. To date, a formal assessment of these MAs has not been performed. The main objective of this systematic review of MAs of PRETHAIs was to evaluate the efficacy of homoeopathic treatment.
METHODS
The inclusion criteria were as follows: MAs of PRETHAIs in humans; all ages, countries, settings, publication languages; and MAs published from 1 Jan. 1990 to 30 Apr. 2023. The exclusion criteria were as follows: systematic reviews without MAs; MAs restricted to age or gender groups, specific indications, or specific homoeopathic treatments; and MAs that did not assess efficacy. We searched 8 electronic databases up to 14 Dec. 2020, with an update search in 6 databases up to 30 April 2023. The primary outcome was the effect estimate for all included trials in each MA and after restricting the sample to trials with high methodological quality, according to predefined criteria. The risk of bias for each MA was assessed by the ROBIS (Risk Of Bias In Systematic reviews) tool. The quality of evidence was assessed by the GRADE framework. Statistical analyses were performed to determine the proportion of MAs showing a significant positive effect of homoeopathy vs. no significant difference.
RESULTS
Six MAs were included, covering individualised homoeopathy (I-HOM, n = 2), nonindividualised homoeopathy (NI-HOM, n = 1) and all homoeopathy types (ALL-HOM = I-HOM + NI-HOM, n = 3). The MAs comprised between 16 and 110 trials, and the included trials were published from 1943-2014. The median trial sample size ranged from 45 to 97 patients. The risk of bias (low/unclear/high) was rated as low for three MAs and high for three MAs. Effect estimates for all trials in each MA showed a significant positive effect of homoeopathy compared to placebo (5 of 5 MAs, no data in 1 MA). Sensitivity analyses with sample restriction to high-quality trials were available from 4 MAs; the effect remained significant in 3 of the MAs (2 MAs assessed ALL-HOM, 1 MA assessed I-HOM) and was no longer significant in 1 MA (which assessed NI-HOM).
DISCUSSION
The quality of evidence for positive effects of homoeopathy beyond placebo (high/moderate/low/very low) was high for I-HOM and moderate for ALL-HOM and NI-HOM. There was no support for the alternative hypothesis of no outcome difference between homoeopathy and placebo. The available MAs of PRETHAIs reveal significant positive effects of homoeopathy beyond placebo. This is in accordance with laboratory experiments showing partially replicable effects of homoeopathically potentised preparations in physico-chemical, in vitro, plant-based and animal-based test systems.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42020209661. The protocol for this SR was finalised and submitted on 25 Nov. 2020 and registered on 26 Dec. 2020.
Topics: Humans; Bias; Homeopathy; Research Design; Meta-Analysis as Topic; Randomized Controlled Trials as Topic
PubMed: 37805577
DOI: 10.1186/s13643-023-02313-2 -
The Cochrane Database of Systematic... Nov 2020Endometriosis is a common gynaecological condition affecting 10% to 15% of reproductive-age women and may cause dyspareunia, dysmenorrhoea, and infertility. One... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Endometriosis is a common gynaecological condition affecting 10% to 15% of reproductive-age women and may cause dyspareunia, dysmenorrhoea, and infertility. One treatment strategy is combining surgery and medical therapy to reduce the recurrence of endometriosis. Though the combination of surgery and medical therapy appears to be beneficial, there is a lack of clarity about the appropriate timing of when medical therapy should be used in relation with surgery, that is, before, after, or both before and after surgery, to maximize treatment response.
OBJECTIVES
To determine the effectiveness of medical therapies for hormonal suppression before, after, or both before and after surgery for endometriosis for improving painful symptoms, reducing disease recurrence, and increasing pregnancy rates.
SEARCH METHODS
We searched the Cochrane Gynaecology and Fertility (CGF) Group trials register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, and two trials registers in November 2019 together with reference checking and contact with study authors and experts in the field to identify additional studies.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) which compared medical therapies for hormonal suppression before, after, or before and after, therapeutic surgery for endometriosis.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed risk of bias. Where possible, we combined data using risk ratio (RR), standardized mean difference or mean difference (MD) and 95% confidence intervals (CI). Primary outcomes were: painful symptoms of endometriosis as measured by a visual analogue scale (VAS) of pain, other validated scales or dichotomous outcomes; and recurrence of disease as evidenced by EEC (Endoscopic Endometriosis Classification), rAFS (revised American Fertility Society), or rASRM (revised American Society for Reproductive Medicine) scores at second-look laparoscopy.
MAIN RESULTS
We included 26 trials with 3457 women with endometriosis. We used the term "surgery alone" to refer to placebo or no medical therapy. Presurgical medical therapy compared with placebo or no medical therapy Compared to surgery alone, we are uncertain if presurgical medical hormonal suppression reduces pain recurrence at 12 months or less (dichotomous) (RR 1.10, 95% CI 0.72 to 1.66; 1 RCT, n = 262; very low-quality evidence) or whether it reduces disease recurrence at 12 months - total (AFS score) (MD -9.6, 95% CI -11.42 to -7.78; 1 RCT, n = 80; very low-quality evidence). We are uncertain if presurgical medical hormonal suppression decreases disease recurrence at 12 months or less (EEC stage) compared to surgery alone (RR 0.88, 95% CI 0.78 to 1.00; 1 RCT, n = 262; very low-quality evidence). We are uncertain if presurgical medical hormonal suppression improves pregnancy rates compared to surgery alone (RR 1.16, 95% CI 0.99 to 1.36; 1 RCT, n = 262; very low-quality evidence). No trials reported pelvic pain at 12 months or less (continuous) or disease recurrence at 12 months or less. Postsurgical medical therapy compared with placebo or no medical therapy We are uncertain about the improvement observed in pelvic pain at 12 months or less (continuous) between postsurgical medical hormonal suppression and surgery alone (MD -0.48, 95% CI -0.64 to -0.31; 4 RCTs, n = 419; I = 94%; very low-quality evidence). We are uncertain if there is a difference in pain recurrence at 12 months or less (dichotomous) between postsurgical medical hormonal suppression and surgery alone (RR 0.85, 95% CI 0.65 to 1.12; 5 RCTs, n = 634; I = 20%; low-quality evidence). We are uncertain if postsurgical medical hormonal suppression improves disease recurrence at 12 months - total (AFS score) compared to surgery alone (MD -2.29, 95% CI -4.01 to -0.57; 1 RCT, n = 51; very low-quality evidence). Disease recurrence at 12 months or less may be reduced with postsurgical medical hormonal suppression compared to surgery alone (RR 0.30, 95% CI 0.17 to 0.54; 4 RCTs, n = 433; I = 58%; low-quality evidence). We are uncertain about the reduction observed in disease recurrence at 12 months or less (EEC stage) between postsurgical medical hormonal suppression and surgery alone (RR 0.80, 95% CI 0.70 to 0.91; 1 RCT, n = 285; very low-quality evidence). Pregnancy rate is probably increased with postsurgical medical hormonal suppression compared to surgery alone (RR 1.22, 95% CI 1.06 to 1.39; 11 RCTs, n = 932; I = 24%; moderate-quality evidence). Pre- and postsurgical medical therapy compared with surgery alone or surgery and placebo There were no trials identified in the search for this comparison. Presurgical medical therapy compared with postsurgical medical therapy We are uncertain about the difference in pain recurrence at 12 months or less (dichotomous) between postsurgical and presurgical medical hormonal suppression therapy (RR 1.40, 95% CI 0.95 to 2.07; 2 RCTs, n = 326; I = 2%; low-quality evidence). We are uncertain about the difference in disease recurrence at 12 months or less (EEC stage) between postsurgical and presurgical medical hormonal suppression therapy (RR 1.10, 95% CI 0.95 to 1.28; 1 RCT, n = 273; very low-quality evidence). We are uncertain about the difference in pregnancy rate between postsurgical and presurgical medical hormonal suppression therapy (RR 1.05, 95% CI 0.91 to 1.21; 1 RCT, n = 273; very low-quality evidence). No trials reported pelvic pain at 12 months or less (continuous), disease recurrence at 12 months - total (AFS score) or disease recurrence at 12 months or less (dichotomous). Postsurgical medical therapy compared with pre- and postsurgical medical therapy There were no trials identified in the search for this comparison. Serious adverse effects for medical therapies reviewed There was insufficient evidence to reach a conclusion regarding serious adverse effects, as no studies reported data suitable for analysis.
AUTHORS' CONCLUSIONS
Our results indicate that the data about the efficacy of medical therapy for endometriosis are inconclusive, related to the timing of hormonal suppression therapy relative to surgery for endometriosis. In our various comparisons of the timing of hormonal suppression therapy, women who receive postsurgical medical therapy compared with no medical therapy or placebo may experience benefit in terms of disease recurrence and pregnancy. There is insufficient evidence regarding hormonal suppression therapy at other time points in relation to surgery for women with endometriosis.
Topics: Adult; Bias; Chemotherapy, Adjuvant; Combined Modality Therapy; Contraceptive Agents, Female; Endometriosis; Estrogen Antagonists; Female; Gonadotropin-Releasing Hormone; Humans; Middle Aged; Pain Measurement; Pelvic Pain; Placebos; Postoperative Care; Pregnancy; Pregnancy Rate; Preoperative Care; Randomized Controlled Trials as Topic; Recurrence; Secondary Prevention; Time Factors; Young Adult
PubMed: 33206374
DOI: 10.1002/14651858.CD003678.pub3 -
The Cochrane Database of Systematic... Feb 2022Ovarian cancer is the sixth most common cancer in women world-wide. Epithelial ovarian cancer (EOC) is the most common; three-quarters of women present when disease has... (Review)
Review
BACKGROUND
Ovarian cancer is the sixth most common cancer in women world-wide. Epithelial ovarian cancer (EOC) is the most common; three-quarters of women present when disease has spread outside the pelvis (stage III or IV). Treatment consists of a combination of surgery and platinum-based chemotherapy. Although initial responses to chemotherapy are good, most women with advanced disease will relapse. PARP (poly (ADP-ribose) polymerase) inhibitors (PARPi), are a type of anticancer treatment that works by preventing cancer cells from repairing DNA damage, especially in those with breast cancer susceptibility gene (BRCA) variants. PARPi offer a different mechanism of anticancer treatment from conventional chemotherapy.
OBJECTIVES
To determine the benefits and risks of poly (ADP-ribose) polymerase) inhibitors (PARPi) for the treatment of epithelial ovarian cancer (EOC).
SEARCH METHODS
We identified randomised controlled trials (RCTs) by searching the Cochrane Central Register of Controlled Trials (Central 2020, Issue 10), Cochrane Gynaecological Cancer Group Trial Register, MEDLINE (1990 to October 2020), Embase (1990 to October 2020), ongoing trials on www.controlled-trials.com/rct, www.clinicaltrials.gov, www.cancer.gov/clinicaltrials, the National Research Register (NRR), FDA database and pharmaceutical industry biomedical literature.
SELECTION CRITERIA
We included trials that randomised women with EOC to PARPi with no treatment, or PARPi versus conventional chemotherapy, or PARPi together with conventional chemotherapy versus conventional chemotherapy alone.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodology. Two review authors independently assessed whether studies met the inclusion criteria. We contacted investigators for additional data. Outcomes included overall survival (OS), objective response rate (ORR), quality of life (QoL) and rate of adverse events.
MAIN RESULTS
We included 15 studies (6109 participants); four (3070 participants) with newly-diagnosed, advanced EOC and 11 (3039 participants) with recurrent EOC. The studies varied in types of comparisons and evaluated PARPi. Eight studies were judged as at low risk of bias in most of the domains. Quality of life data were generally poorly reported. Below we present six key comparisons. The majority of participants had BRCA mutations, either in their tumour (sBRCAmut) and/or germline (gBRCAmut), or homologous recombination deficiencies (HRD) in their tumours. Newly diagnosed EOC Overall, four studies evaluated the effect of PARPi in newly-diagnosed, advanced EOC. Two compared PARPi with chemotherapy and chemotherapy alone. OS data were not reported. The combination of PARPi with chemotherapy may have little to no difference in progression-free survival (PFS) (two studies, 1564 participants; hazard ratio (HR) 0.82, 95% confidence interval (CI 0).49 to 1.38; very low-certainty evidence)(no evidence of disease progression at 12 months' 63% with PARPi versus 69% for placebo). PARPi with chemotherapy likely increases any severe adverse event (SevAE) (grade 3 or higher) slightly (45%) compared with chemotherapy alone (51%) (two studies, 1549 participants, risk ratio (RR) 1.13, 95% CI 1.07 to 1.20; high-certainty evidence). PARPi combined with chemotherapy compared with chemotherapy alone likely results in little to no difference in the QoL (one study; 744 participants, MD 1.56 95% CI -0.42 to 3.54; moderate-certainty evidence). Two studies compared PARPi monotherapy with placebo as maintenance after first-line chemotherapy in newly diagnosed EOC. PARPi probably results in little to no difference in OS (two studies, 1124 participants; HR 0.81, 95%CI 0.59 to 1.13; moderate-certainty evidence) (alive at 12 months 68% with PARPi versus 62% for placebo). However, PARPi may increase PFS (two studies, 1124 participants; HR 0.42, 95% CI 0.19 to 0.92; low-certainty evidence) (no evidence of disease progression at 12 months' 55% with PARPi versus 24% for placebo). There may be an increase in the risk of experiencing any SevAE (grade 3 or higher) with PARPi (54%) compared with placebo (19%)(two studies, 1118 participants, RR 2.87, 95% CI 1.65 to 4.99; very low-certainty evidence), but the evidence is very uncertain. There is probably a slight reduction in QoL with PARPi, although this may not be clinically significant (one study, 362 participants; MD -3.00, 95%CI -4.48 to -1.52; moderate-certainty evidence). Recurrent, platinum-sensitive EOC Overall, 10 studies evaluated the effect of PARPi in recurrent platinum-sensitive EOC. Three studies compared PARPi monotherapy with chemotherapy alone. PARPi may result in little to no difference in OS (two studies, 331 participants; HR 0.95, 95%CI 0.62 to 1.47; low-certainty evidence) (percentage alive at 36 months 18% with PARPi versus 17% for placebo). Evidence is very uncertain about the effect of PARPi on PFS (three studies, 739 participants; HR 0.88, 95%CI 0.56 to 1.38; very low-certainty evidence)(no evidence of disease progression at 12 months 26% with PARPi versus 22% for placebo). There may be little to no difference in rates of any SevAE (grade 3 or higher) with PARPi (50%) than chemotherapy alone (47%) (one study, 254 participants; RR 1.06, 95%CI 0.80 to 1.39; low-certainty evidence). Four studies compared PARPi monotherapy as maintenance with placebo. PARPi may result in little to no difference in OS (two studies, 560 participants; HR 0.88, 95%CI 0.65 to 1.20; moderate-certainty evidence)(percentage alive at 36 months 21% with PARPi versus 17% for placebo). However, evidence suggests that PARPi as maintenance therapy results in a large PFS (four studies, 1677 participants; HR 0.34, 95% CI 0.28 to 0.42; high-certainty evidence)(no evidence of disease progression at 12 months 37% with PARPi versus 5.5% for placebo). PARPi maintenance therapy may result in a large increase in any SevAE (51%) (grade 3 or higher) than placebo (19%)(four studies, 1665 participants, RR 2.62, 95%CI 1.85 to 3.72; low-certainty evidence). PARPi compared with chemotherapy may result in little or no change in QoL (one study, 229 participants, MD 1.20, 95%CI -1.75 to 4.16; low-certainty evidence). Recurrent, platinum-resistant EOC Two studies compared PARPi with chemotherapy. The certainty of evidence in both studies was graded as very low. Overall, there was minimal information on the QoL and adverse events.
AUTHORS' CONCLUSIONS
PARPi maintenance treatment after chemotherapy may improve PFS in women with newly-diagnosed and recurrent platinum-sensitive EOC; there may be little to no effect on OS, although OS data are immature. Overall, this is likely at the expense of an increase in SevAE. It is disappointing that data on quality of life outcomes are relatively sparse. More research is needed to determine whether PARPi have a role to play in platinum-resistant disease.
Topics: Carcinoma, Ovarian Epithelial; Female; Humans; Neoplasm Recurrence, Local; Ovarian Neoplasms; Poly(ADP-ribose) Polymerase Inhibitors; Poly(ADP-ribose) Polymerases
PubMed: 35170751
DOI: 10.1002/14651858.CD007929.pub4 -
Schizophrenia Bulletin Jan 2024Long-acting injectable antipsychotic drugs (LAIs) are mainly used for relapse prevention but could also be advantageous for acutely ill patients with schizophrenia. (Meta-Analysis)
Meta-Analysis
Long-Acting Injectable Second-Generation Antipsychotics vs Placebo and Their Oral Formulations in Acute Schizophrenia: A Systematic Review and Meta-Analysis of Randomized-Controlled-Trials.
BACKGROUND AND HYPOTHESIS
Long-acting injectable antipsychotic drugs (LAIs) are mainly used for relapse prevention but could also be advantageous for acutely ill patients with schizophrenia.
STUDY DESIGN
We conducted a systematic review and meta-analysis of randomized-controlled-trials (RCTs) comparing the second-generation long-acting injectable antipsychotics (SGA-LAIs) olanzapine, risperidone, paliperidone, and aripiprazole with placebo or their oral counterparts in acutely ill patients with schizophrenia. We analyzed 23 efficacy and tolerability outcomes, with the primary outcome being overall symptoms of schizophrenia. The results were obtained through random effects, pairwise meta-analyses, and subgroup tests. The study quality was assessed using the Cochrane-Risk-of-Bias-Tool version-1.
STUDY RESULTS
Sixty-six studies with 16 457 participants were included in the analysis. Eleven studies compared second-generation long-acting injectable antipsychotics (SGA-LAIs) with a placebo, 54 compared second-generation oral antipsychotics (SGA-orals) with a placebo, and one compared an SGA-LAI (aripiprazole) with its oral formulation. All 4 SGA-LAIs reduced overall symptoms more than placebo, with mean standardized differences of -0.66 (95% CI: -0.90; -0.43) for olanzapine, -0.64 (-0.80; -0.48) for aripiprazole, -0.62 (-0.76; -0.48) for risperidone and -0.42 (-0.53; -0.31) for paliperidone. The side-effect profiles of the LAIs corresponded to the patterns known from the oral formulations. In subgroup tests compared to placebo, some side effects were less pronounced under LAIs than under their oral formulations.
CONCLUSIONS
SGA-LAIs effectively treat acute schizophrenia. Some side effects may be less frequent than under oral drugs, but due to the indirect nature of the comparisons, this finding must be confirmed by RCTs comparing LAIs and orals head-to-head.
Topics: Humans; Antipsychotic Agents; Paliperidone Palmitate; Aripiprazole; Olanzapine; Risperidone; Delayed-Action Preparations; Schizophrenia
PubMed: 37350486
DOI: 10.1093/schbul/sbad089 -
BioMed Research International 2020Osteoarthritis is the most common musculoskeletal disease. Extracorporeal shockwave therapy had shown an effect on osteoarthritis in both some animal experiments and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Osteoarthritis is the most common musculoskeletal disease. Extracorporeal shockwave therapy had shown an effect on osteoarthritis in both some animal experiments and clinical studies, but there was no systematic review to confirm the value of shockwave therapy in the treatment of all types of osteoarthritis and compare it with other traditional therapies (especially traditional Chinese medicine).
METHOD
PubMed, Medline, the Cochrane Central Register of Controlled Trials, Web of Science, Chinese National Knowledge Infrastructure, WANFANG database, and VIP database were searched up to December 10, 2019, to identify randomized controlled trials comparing shockwave therapy and other treatments for osteoarthritis. Visual analogue scale and the Western Ontario and McMaster Universities Osteoarthritis Index were extracted and analyzed by RevMan and STATA software as outcomes of pain reduction and functional improvement. Adverse reactions were recorded to evaluate the safety of shockwave therapy.
RESULTS
Shockwave therapy had significant improvement in both pain reduction and functional improvement compared with placebo, corticosteroid, hyaluronic acid, medication, and ultrasound ( < 0.05). In functional improvement, shockwave therapy showed statistical improvement compared with kinesiotherapy and moxibustion ( < 0.05) but not with acupotomy surgery ( = 0.24). A significant difference between shockwave therapy and platelet-rich plasma was observed in pain reduction ( < 0.05) but not in functional improvement ( = 0.89). Meanwhile, a statistical difference was found between shockwave therapy and fumigation in functional improvement ( < 0.05) but not in pain reduction ( = 0.26). Additionally, there was no statistically significant difference between shockwave therapy and manipulation in both pain reduction ( = 0.21) and functional improvement ( = 0.45). No serious adverse reaction occurred in all of studies.
CONCLUSIONS
Extracorporeal shockwave therapy could be recommended in the treatment of osteoarthritis as a noninvasive therapy with safety and effectiveness, but the grade of recommendations needs to be discussed in a further study.
Topics: Animals; Databases, Factual; Extracorporeal Shockwave Therapy; Humans; Hyaluronic Acid; Injections, Intra-Articular; Medicine, Chinese Traditional; Osteoarthritis; Osteoarthritis, Knee; Pain; Pain Measurement; Placebos; Platelet-Rich Plasma; Ultrasonic Therapy
PubMed: 32309424
DOI: 10.1155/2020/1907821 -
The Cochrane Database of Systematic... Jan 2021Chronic obstructive pulmonary disease (COPD) is a chronic respiratory condition characterised by persistent respiratory symptoms and airflow limitation. Acute... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Chronic obstructive pulmonary disease (COPD) is a chronic respiratory condition characterised by persistent respiratory symptoms and airflow limitation. Acute exacerbations punctuate the natural history of COPD and are associated with increased morbidity and mortality and disease progression. Chronic airflow limitation is caused by a combination of small airways (bronchitis) and parenchymal destruction (emphysema), which can impact day-to-day activities and overall quality of life. In carefully selected patients with COPD, long-term, prophylactic use of antibiotics may reduce bacterial load, inflammation of the airways, and the frequency of exacerbations.
OBJECTIVES
To assess effects of different prophylactic antibiotics on exacerbations, quality of life, and serious adverse events in people with COPD in three separate network meta-analyses (NMAs), and to provide rankings of identified antibiotics.
SEARCH METHODS
To identify eligible randomised controlled trials (RCTs), we searched the Cochrane Airways Group Specialised Register of trials and clinical trials registries. We conducted the most recent search on 22 January 2020.
SELECTION CRITERIA
We included RCTs with a parallel design of at least 12 weeks' duration evaluating long-term administration of antibiotics prophylactically compared with other antibiotics, or placebo, for patients with COPD.
DATA COLLECTION AND ANALYSIS
This Cochrane Review collected and updated pair-wise data from two previous Cochrane Reviews. Searches were updated and additional studies included. We conducted three separate network meta-analyses (NMAs) within a Bayesian framework to assess three outcomes: exacerbations, quality of life, and serious adverse events. For quality of life, we collected data from St George's Respiratory Questionnaire (SGRQ). Using previously validated methods, we selected the simplest model that could adequately fit the data for every analysis. We used threshold analysis to indicate which results were robust to potential biases, taking into account each study's contributions to the overall results and network structure. Probability ranking was performed for each antibiotic class for exacerbations, quality of life, and serious adverse events.
MAIN RESULTS
Characteristics of studies and participants Eight trials were conducted at multiple sites that included hospital clinics or academic health centres. Seven were single-centre trials conducted in hospital clinics. Two trials did not report settings. Trials durations ranged from 12 to 52 weeks. Most participants had moderate to severe disease. Mean age ranged from 64 years to 73 years, and more males were recruited (51% to 100%). Forced expiratory volume in one second (FEV₁) ranged from 0.935 to 1.36 L. Most participants had previous exacerbations. Data from 12 studies were included in the NMAs (3405 participants; 16 treatment arms including placebo). Prophylactic antibiotics evaluated were macrolides (azithromycin and erythromycin), tetracyclines (doxycyclines), quinolones (moxifloxacin) and macrolides plus tetracyclines (roxithromycin plus doxycycline). Risk of bias and threshold analysis Most studies were at low risk across domains, except detection bias, for which only seven studies were judged at low risk. In the threshold analysis for exacerbations, all comparisons in which one antibiotic was compared with another were robust to sampling variation, especially macrolide comparisons. Comparisons of classes with placebo were sensitive to potential bias, especially macrolide versus placebo, therefore, any bias in the comparison was likely to favour the active class, so any adjustment would bring the estimated relative effect closer to the null value, thus quinolone may become the best class to prevent exacerbations. Exacerbations Nine studies were included (2732 participants) in this NMA (exacerbations analysed as time to first exacerbation or people with one or more exacerbations). Macrolides and quinolones reduced exacerbations. Macrolides had a greater effect in reducing exacerbations compared with placebo (macrolides: hazard ratio (HR) 0.67, 95% credible interval (CrI) 0.60 to 0.75; quinolones: HR 0.89, 95% CrI 0.75 to 1.04), resulting in 127 fewer people per 1000 experiencing exacerbations on macrolides. The difference in exacerbations between tetracyclines and placebo was uncertain (HR 1.29, 95% CrI 0.66 to 2.41). Macrolides ranked first (95% CrI first to second), with quinolones ranked second (95% CrI second to third). Tetracyclines ranked fourth, which was lower than placebo (ranked third). Contributing studies were considered as low risk of bias in a threshold analysis. Quality of life (SGRQ) Seven studies were included (2237 participants) in this NMA. SGRQ scores improved with macrolide treatment compared with placebo (fixed effect-fixed class effect: mean difference (MD) -2.30, 95% CrI -3.61 to -0.99), but the mean difference did not reach the minimally clinical important difference (MCID) of 4 points. Tetracyclines and quinolones did not improve quality of life any more than placebo, and we did not detect a difference between antibiotic classes. Serious adverse events Nine studies were included (3180 participants) in the NMA. Macrolides reduced the odds of a serious adverse event compared with placebo (fixed effect-fixed class effect: odds ratio (OR) 0.76, 95% CrI 0.62 to 0.93). There was probably little to no difference in the effect of quinolone compared with placebo or tetracycline plus macrolide compared with placebo. There was probably little to no difference in serious adverse events between quinolones or tetracycline plus macrolide. With macrolide treatment 49 fewer people per 1000 experienced a serious adverse event compared with those given placebo. Macrolides ranked first, followed by quinolones. Tetracycline did not rank better than placebo. Drug resistance Ten studies reported drug resistance. Results were not combined due to variation in outcome measures. All studies concluded that prophylactic antibiotic administration was associated with the development of antimicrobial resistance.
AUTHORS' CONCLUSIONS
This NMA evaluated the safety and efficacy of different antibiotics used prophylactically for COPD patients. Compared to placebo, prolonged administration of macrolides (ranked first) appeared beneficial in prolonging the time to next exacerbation, improving quality of life, and reducing serious adverse events. No clear benefits were associated with use of quinolones or tetracyclines. In addition, antibiotic resistance was a concern and could not be thoroughly assessed in this review. Given the trade-off between effectiveness, safety, and risk of antibiotic resistance, prophylactic administration of antibiotics may be best reserved for selected patients, such as those experiencing frequent exacerbations. However, none of the eligible studies excluded patients with previously isolated non-tuberculous mycobacteria, which would contraindicate prophylactic administration of antibiotics, due to the risk of developing resistant non-tuberculous mycobacteria.
Topics: Adult; Aged; Anti-Bacterial Agents; Antibiotic Prophylaxis; Bacterial Load; Bayes Theorem; Bias; Disease Progression; Female; Forced Expiratory Volume; Humans; Macrolides; Male; Middle Aged; Network Meta-Analysis; Pulmonary Disease, Chronic Obstructive; Quality of Life; Quinolones; Randomized Controlled Trials as Topic; Tetracyclines; Treatment Outcome
PubMed: 33448349
DOI: 10.1002/14651858.CD013198.pub2 -
The Cochrane Database of Systematic... Feb 2021Vascular cognitive impairment (VCI) describes a broad spectrum of cognitive impairments caused by cerebrovascular disease, ranging from mild cognitive impairment to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Vascular cognitive impairment (VCI) describes a broad spectrum of cognitive impairments caused by cerebrovascular disease, ranging from mild cognitive impairment to dementia. There are currently no pharmacological treatments recommended for improving either cognition or function in people with VCI. Three cholinesterase inhibitors (donepezil, galantamine, and rivastigmine) are licenced for the treatment of dementia due to Alzheimer's disease. They are thought to work by compensating for reduced cholinergic neurotransmission, which is also a feature of VCI. Through pairwise comparisons with placebo and a network meta-analysis, we sought to determine whether these medications are effective in VCI and whether there are differences between them with regard to efficacy or adverse events.
OBJECTIVES
(1) To assess the efficacy and safety of cholinesterase inhibitors in the treatment of adults with vascular dementia and other VCI. (2) To compare the effects of different cholinesterase inhibitors on cognition and adverse events, using network meta-analysis.
SEARCH METHODS
We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group's register, MEDLINE (OvidSP), Embase (OvidSP), PsycINFO (OvidSP), CINAHL (EBSCOhost), Web of Science Core Collection (ISI Web of Science), LILACS (BIREME), ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform on 19 August 2020.
SELECTION CRITERIA
We included randomised controlled trials in which donepezil, galantamine, or rivastigmine was compared with placebo or in which the drugs were compared with each other in adults with vascular dementia or other VCI (excluding cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)). We included all drug doses and routes of administration.
DATA COLLECTION AND ANALYSIS
Two review authors independently identified eligible trials, extracted data, assessed risk of bias, and applied the GRADE approach to assess the certainty of the evidence. The primary outcomes were cognition, clinical global impression, function (performance of activities of daily living), and adverse events. Secondary outcomes were serious adverse events, incidence of development of new dementia, behavioural disturbance, carer burden, institutionalisation, quality of life and death. For the pairwise analyses, we pooled outcome data at similar time points using random-effects methods. We also performed a network meta-analysis using Bayesian methods.
MAIN RESULTS
We included eight trials (4373 participants) in the review. Three trials studied donepezil 5 mg or 10 mg daily (n= 2193); three trials studied rivastigmine at a maximum daily dose of 3 to 12 mg (n= 800); and two trials studied galantamine at a maximum daily dose of 16 to 24 mg (n= 1380). The trials included participants with possible or probable vascular dementia or cognitive impairment following stroke. Mean ages were between 72.2 and 73.9 years. All of the trials were at low or unclear risk of bias in all domains, and the evidence ranged from very low to high level of certainty. For cognition, the results showed that donepezil 5 mg improves cognition slightly, although the size of the effect is unlikely to be clinically important (mean difference (MD) -0.92 Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) points (range 0 to 70), 95% confidence interval (CI) -1.44 to -0.40; high-certainty evidence). Donepezil 10 mg (MD -2.21 ADAS-Cog points, 95% CI -3.07 to -1.35; moderate-certainty evidence) and galantamine 16 to 24 mg (MD -2.01 ADAS-Cog point, 95%CI -3.18 to -0.85; moderate-certainty evidence) probably also improve cognition, although the larger effect estimates still may not be clinically important. With low certainty, there may be little to no effect of rivastigmine 3 to 12 mg daily on cognition (MD 0.03 ADAS-Cog points, 95% CI -3.04 to 3.10; low-certainty evidence). Adverse events reported in the studies included nausea and/or vomiting, diarrhoea, dizziness, headache, and hypertension. The results showed that there was probably little to no difference between donepezil 5 mg and placebo in the number of adverse events (odds ratio (OR) 1.22, 95% CI 0.94 to 1.58; moderate-certainty evidence), but there were slightly more adverse events with donepezil 10 mg than with placebo (OR 1.95, 95% CI 1.20 to 3.15; high-certainty evidence). The effect of rivastigmine 3 to 12 mg on adverse events was very uncertain (OR 3.21, 95% CI 0.36 to 28.88; very low-certainty evidence). Galantamine 16 to 24 mg is probably associated with a slight excess of adverse events over placebo (OR 1.57, 95% CI 1.02 to 2.43; moderate-certainty evidence). In the network meta-analysis (NMA), we included cognition to represent benefit, and adverse events to represent harm. All drugs ranked above placebo for cognition and below placebo for adverse events. We found donepezil 10 mg to rank first in terms of benefit, but third in terms of harms, when considering the network estimates and quality of evidence. Galantamine was ranked second in terms of both benefit and harm. Rivastigmine had the lowest ranking of the cholinesterase inhibitors in both benefit and harm NMA estimates, but this may reflect possibly inadequate doses received by some trial participants and small trial sample sizes.
AUTHORS' CONCLUSIONS
We found moderate- to high-certainty evidence that donepezil 5 mg, donepezil 10 mg, and galantamine have a slight beneficial effect on cognition in people with VCI, although the size of the change is unlikely to be clinically important. Donepezil 10 mg and galantamine 16 to 24 mg are probably associated with more adverse events than placebo. The evidence for rivastigmine was less certain. The data suggest that donepezil 10 mg has the greatest effect on cognition, but at the cost of adverse effects. The effect is modest, but in the absence of any other treatments, people living with VCI may still wish to consider the use of these agents. Further research into rivastigmine is needed, including the use of transdermal patches.
Topics: Activities of Daily Living; Bias; Cholinesterase Inhibitors; Cognition; Dementia, Vascular; Donepezil; Galantamine; Humans; Network Meta-Analysis; Nootropic Agents; Physical Functional Performance; Placebos; Randomized Controlled Trials as Topic; Rivastigmine
PubMed: 33704781
DOI: 10.1002/14651858.CD013306.pub2 -
The Cochrane Database of Systematic... Apr 2023Attention deficit hyperactivity disorder (ADHD) is a major problem in children and adolescents, characterised by age-inappropriate levels of inattention, hyperactivity,... (Review)
Review
BACKGROUND
Attention deficit hyperactivity disorder (ADHD) is a major problem in children and adolescents, characterised by age-inappropriate levels of inattention, hyperactivity, and impulsivity, and is associated with long-term social, academic, and mental health problems. The stimulant medications methylphenidate and amphetamine are the most frequently used treatments for ADHD, but these are not always effective and can be associated with side effects. Clinical and biochemical evidence suggests that deficiencies of polyunsaturated fatty acids (PUFA) could be related to ADHD. Research has shown that children and adolescents with ADHD have significantly lower plasma and blood concentrations of PUFA and, in particular, lower levels of omega-3 PUFA. These findings suggest that PUFA supplementation may reduce the attention and behaviour problems associated with ADHD. This review is an update of a previously published Cochrane Review. Overall, there was little evidence that PUFA supplementation improved symptoms of ADHD in children and adolescents.
OBJECTIVES
To compare the efficacy of PUFA to other forms of treatment or placebo in treating the symptoms of ADHD in children and adolescents.
SEARCH METHODS
We searched 13 databases and two trials registers up to October 2021. We also checked the reference lists of relevant studies and reviews for additional references.
SELECTION CRITERIA
We included randomised and quasi-randomised controlled trials that compared PUFA with placebo or PUFA plus alternative therapy (medication, behavioural therapy, or psychotherapy) with the same alternative therapy alone in children and adolescents (aged 18 years and under) diagnosed with ADHD.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcome was severity or improvement of ADHD symptoms. Our secondary outcomes were severity or incidence of behavioural problems; quality of life; severity or incidence of depressive symptoms; severity or incidence of anxiety symptoms; side effects; loss to follow-up; and cost. We used GRADE to assess the certainty of evidence for each outcome.
MAIN RESULTS
We included 37 trials with more than 2374 participants, of which 24 trials were new to this update. Five trials (seven reports) used a cross-over design, while the remaining 32 trials (52 reports) used a parallel design. Seven trials were conducted in Iran, four each in the USA and Israel, and two each in Australia, Canada, New Zealand, Sweden, and the UK. Single studies were conducted in Brazil, France, Germany, India, Italy, Japan, Mexico, the Netherlands, Singapore, Spain, Sri Lanka, and Taiwan. Of the 36 trials that compared a PUFA to placebo, 19 used an omega-3 PUFA, six used a combined omega-3/omega-6 supplement, and two used an omega-6 PUFA. The nine remaining trials were included in the comparison of PUFA to placebo, but also had the same co-intervention in the PUFA and placebo groups. Of these, four trials compared a combination of omega-3 PUFA plus methylphenidate to methylphenidate. One trial each compared omega-3 PUFA plus atomoxetine to atomoxetine; omega-3 PUFA plus physical training to physical training; and an omega-3 or omega-6 supplement plus methylphenidate to methylphenidate; and two trials compared omega-3 PUFA plus dietary supplement to dietary supplement. Supplements were given for a period of between two weeks and six months. Although we found low-certainty evidence that PUFA compared to placebo may improve ADHD symptoms in the medium term (risk ratio (RR) 1.95, 95% confidence interval (CI) 1.47 to 2.60; 3 studies, 191 participants), there was high-certainty evidence that PUFA had no effect on parent-rated total ADHD symptoms compared to placebo in the medium term (standardised mean difference (SMD) -0.08, 95% CI -0.24 to 0.07; 16 studies, 1166 participants). There was also high-certainty evidence that parent-rated inattention (medium-term: SMD -0.01, 95% CI -0.20 to 0.17; 12 studies, 960 participants) and hyperactivity/impulsivity (medium-term: SMD 0.09, 95% CI -0.04 to 0.23; 10 studies, 869 participants) scores were no different compared to placebo. There was moderate-certainty evidence that overall side effects likely did not differ between PUFA and placebo groups (RR 1.02, 95% CI 0.69 to 1.52; 8 studies, 591 participants). There was also moderate-certainty evidence that medium-term loss to follow-up was likely similar between groups (RR 1.03, 95% CI 0.77 to 1.37; 13 studies, 1121 participants).
AUTHORS' CONCLUSIONS
Although we found low-certainty evidence that children and adolescents receiving PUFA may be more likely to improve compared to those receiving placebo, there was high-certainty evidence that PUFA had no effect on total parent-rated ADHD symptoms. There was also high-certainty evidence that inattention and hyperactivity/impulsivity did not differ between PUFA and placebo groups. We found moderate-certainty evidence that overall side effects likely did not differ between PUFA and placebo groups. There was also moderate-certainty evidence that follow-up was similar between groups. It is important that future research addresses the current weaknesses in this area, which include small sample sizes, variability of selection criteria, variability of the type and dosage of supplementation, and short follow-up times.
Topics: Child; Humans; Adolescent; Attention Deficit Disorder with Hyperactivity; Atomoxetine Hydrochloride; Quality of Life; Fatty Acids, Unsaturated; Methylphenidate; Fatty Acids, Omega-3; Amphetamine
PubMed: 37058600
DOI: 10.1002/14651858.CD007986.pub3 -
The Cochrane Database of Systematic... Sep 2020Pain after caesarean sections (CS) can affect the well-being of the mother and her ability with her newborn. Conventional pain-relieving strategies are often underused... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pain after caesarean sections (CS) can affect the well-being of the mother and her ability with her newborn. Conventional pain-relieving strategies are often underused because of concerns about the adverse maternal and neonatal effects. Complementary alternative therapies (CAM) may offer an alternative for post-CS pain.
OBJECTIVES
To assess the effects of CAM for post-caesarean pain.
SEARCH METHODS
We searched Cochrane Pregnancy and Childbirth's Trials Register, LILACS, PEDro, CAMbase, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) (6 September 2019), and checked the reference lists of retrieved articles.
SELECTION CRITERIA
Randomised controlled trials (RCTs), including quasi-RCTs and cluster-RCTs, comparing CAM, alone or associated with other forms of pain relief, versus other treatments or placebo or no treatment, for the treatment of post-CS pain.
DATA COLLECTION AND ANALYSIS
Two review authors independently performed study selection, extracted data, assessed risk of bias and assessed the certainty of evidence using GRADE.
MAIN RESULTS
We included 37 studies (3076 women) which investigated eight different CAM therapies for post-CS pain relief. There is substantial heterogeneity among the trials. We downgraded the certainty of evidence due to small numbers of women participating in the trials and to risk of bias related to lack of blinding and inadequate reporting of randomisation processes. None of the trials reported pain at six weeks after discharge. Primary outcomes were pain and adverse effects, reported per intervention below. Secondary outcomes included vital signs, rescue analgesic requirement at six weeks after discharge; all of which were poorly reported, not reported, or we are uncertain as to the effect Acupuncture or acupressure We are very uncertain if acupuncture or acupressure (versus no treatment) or acupuncture or acupressure plus analgesia (versus placebo plus analgesia) has any effect on pain because the quality of evidence is very low. Acupuncture or acupressure plus analgesia (versus analgesia) may reduce pain at 12 hours (standardised mean difference (SMD) -0.28, 95% confidence interval (CI) -0.64 to 0.07; 130 women; 2 studies; low-certainty evidence) and 24 hours (SMD -0.63, 95% CI -0.99 to -0.26; 2 studies; 130 women; low-certainty evidence). It is uncertain whether acupuncture or acupressure (versus no treatment) or acupuncture or acupressure plus analgesia (versus analgesia) has any effect on the risk of adverse effects because the quality of evidence is very low. Aromatherapy Aromatherapy plus analgesia may reduce pain when compared with placebo plus analgesia at 12 hours (mean difference (MD) -2.63 visual analogue scale (VAS), 95% CI -3.48 to -1.77; 3 studies; 360 women; low-certainty evidence) and 24 hours (MD -3.38 VAS, 95% CI -3.85 to -2.91; 1 study; 200 women; low-certainty evidence). We are uncertain if aromatherapy plus analgesia has any effect on adverse effects (anxiety) compared with placebo plus analgesia. Electromagnetic therapy Electromagnetic therapy may reduce pain compared with placebo plus analgesia at 12 hours (MD -8.00, 95% CI -11.65 to -4.35; 1 study; 72 women; low-certainty evidence) and 24 hours (MD -13.00 VAS, 95% CI -17.13 to -8.87; 1 study; 72 women; low-certainty evidence). Massage We identified six studies (651 women), five of which were quasi-RCTs, comparing massage (foot and hand) plus analgesia versus analgesia. All the evidence relating to pain, adverse effects (anxiety), vital signs and rescue analgesic requirement was very low-certainty. Music Music plus analgesia may reduce pain when compared with placebo plus analgesia at one hour (SMD -0.84, 95% CI -1.23 to -0.46; participants = 115; studies = 2; I = 0%; low-certainty evidence), 24 hours (MD -1.79, 95% CI -2.67 to -0.91; 1 study; 38 women; low-certainty evidence), and also when compared with analgesia at one hour (MD -2.11, 95% CI -3.11 to -1.10; 1 study; 38 women; low-certainty evidence) and at 24 hours (MD -2.69, 95% CI -3.67 to -1.70; 1 study; 38 women; low-certainty evidence). It is uncertain whether music plus analgesia has any effect on adverse effects (anxiety), when compared with placebo plus analgesia because the quality of evidence is very low. Reiki We are uncertain if Reiki plus analgesia compared with analgesia alone has any effect on pain, adverse effects, vital signs or rescue analgesic requirement because the quality of evidence is very low (one study, 90 women). Relaxation Relaxation may reduce pain compared with standard care at 24 hours (MD -0.53 VAS, 95% CI -1.05 to -0.01; 1 study; 60 women; low-certainty evidence). Transcutaneous electrical nerve stimulation TENS (versus no treatment) may reduce pain at one hour (MD -2.26, 95% CI -3.35 to -1.17; 1 study; 40 women; low-certainty evidence). TENS plus analgesia (versus placebo plus analgesia) may reduce pain compared with placebo plus analgesia at one hour (SMD -1.10 VAS, 95% CI -1.37 to -0.82; 3 studies; 238 women; low-certainty evidence) and at 24 hours (MD -0.70 VAS, 95% CI -0.87 to -0.53; 108 women; 1 study; low-certainty evidence). TENS plus analgesia (versus placebo plus analgesia) may reduce heart rate (MD -7.00 bpm, 95% CI -7.63 to -6.37; 108 women; 1 study; low-certainty evidence) and respiratory rate (MD -1.10 brpm, 95% CI -1.26 to -0.94; 108 women; 1 study; low-certainty evidence). We are uncertain if TENS plus analgesia (versus analgesia) has any effect on pain at six hours or 24 hours, or vital signs because the quality of evidence is very low (two studies, 92 women).
AUTHORS' CONCLUSIONS
Some CAM therapies may help reduce post-CS pain for up to 24 hours. The evidence on adverse events is too uncertain to make any judgements on safety and we have no evidence about the longer-term effects on pain. Since pain control is the most relevant outcome for post-CS women and their clinicians, it is important that future studies of CAM for post-CS pain measure pain as a primary outcome, preferably as the proportion of participants with at least moderate (30%) or substantial (50%) pain relief. Measuring pain as a dichotomous variable would improve the certainty of evidence and it is easy to understand for non-specialists. Future trials also need to be large enough to detect effects on clinical outcomes; measure other important outcomes as listed lin this review, and use validated scales.
Topics: Acupressure; Acupuncture Analgesia; Adolescent; Adult; Analgesia, Obstetrical; Analgesics; Aromatherapy; Bias; Cesarean Section; Combined Modality Therapy; Complementary Therapies; Female; Humans; Massage; Music Therapy; Pain, Postoperative; Placebos; Pregnancy; Randomized Controlled Trials as Topic; Relaxation Therapy; Therapeutic Touch; Transcutaneous Electric Nerve Stimulation; Young Adult
PubMed: 32871021
DOI: 10.1002/14651858.CD011216.pub2 -
The Cochrane Database of Systematic... Jun 2021Misoprostol given orally is a commonly used labour induction method. Our Cochrane Review is restricted to studies with low-dose misoprostol (initially ≤ 50 µg), as... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Misoprostol given orally is a commonly used labour induction method. Our Cochrane Review is restricted to studies with low-dose misoprostol (initially ≤ 50 µg), as higher doses pose unacceptably high risks of uterine hyperstimulation.
OBJECTIVES
To assess the efficacy and safety of low-dose oral misoprostol for labour induction in women with a viable fetus in the third trimester of pregnancy.
SEARCH METHODS
We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (14 February 2021) and reference lists of retrieved studies.
SELECTION CRITERIA
Randomised trials comparing low-dose oral misoprostol (initial dose ≤ 50 µg) versus placebo, vaginal dinoprostone, vaginal misoprostol, oxytocin, or mechanical methods; or comparing oral misoprostol protocols (one- to two-hourly versus four- to six-hourly; 20 µg to 25 µg versus 50 µg; or 20 µg hourly titrated versus 25 µg two-hourly static).
DATA COLLECTION AND ANALYSIS
Using Covidence, two review authors independently screened reports, extracted trial data, and performed quality assessments. Our primary outcomes were vaginal birth within 24 hours, caesarean section, and hyperstimulation with foetal heart changes.
MAIN RESULTS
We included 61 trials involving 20,026 women. GRADE assessments ranged from moderate- to very low-certainty evidence, with downgrading decisions based on imprecision, inconsistency, and study limitations. Oral misoprostol versus placebo/no treatment (four trials; 594 women) Oral misoprostol may make little to no difference in the rate of caesarean section (risk ratio (RR) 0.81, 95% confidence interval (CI) 0.59 to 1.11; 4 trials; 594 women; moderate-certainty evidence), while its effect on uterine hyperstimulation with foetal heart rate changes is uncertain (RR 5.15, 95% CI 0.25 to 105.31; 3 trials; 495 women; very low-certainty evidence). Vaginal births within 24 hours was not reported. In all trials, oxytocin could be commenced after 12 to 24 hours and all women had pre-labour ruptured membranes. Oral misoprostol versus vaginal dinoprostone (13 trials; 9676 women) Oral misoprostol probably results in fewer caesarean sections (RR 0.84, 95% CI 0.78 to 0.90; 13 trials, 9676 women; moderate-certainty evidence). Subgroup analysis indicated that 10 µg to 25 µg (RR 0.80, 95% CI 0.74 to 0.87; 9 trials; 8652 women) may differ from 50 µg (RR 1.10, 95% CI 0.91 to 1.34; 4 trials; 1024 women) for caesarean section. Oral misoprostol may decrease vaginal births within 24 hours (RR 0.93, 95% CI 0.87 to 1.00; 10 trials; 8983 women; low-certainty evidence) and hyperstimulation with foetal heart rate changes (RR 0.49, 95% CI 0.40 to 0.59; 11 trials; 9084 women; low-certainty evidence). Oral misoprostol versus vaginal misoprostol (33 trials; 6110 women) Oral use may result in fewer vaginal births within 24 hours (average RR 0.81, 95% CI 0.68 to 0.95; 16 trials, 3451 women; low-certainty evidence), and less hyperstimulation with foetal heart rate changes (RR 0.69, 95% CI 0.53 to 0.92, 25 trials, 4857 women, low-certainty evidence), with subgroup analysis suggesting that 10 µg to 25 µg orally (RR 0.28, 95% CI 0.14 to 0.57; 6 trials, 957 women) may be superior to 50 µg orally (RR 0.82, 95% CI 0.61 to 1.11; 19 trials; 3900 women). Oral misoprostol probably does not increase caesarean sections overall (average RR 1.00, 95% CI 0.86 to 1.16; 32 trials; 5914 women; low-certainty evidence) but likely results in fewer caesareans for foetal distress (RR 0.74, 95% CI 0.55 to 0.99; 24 trials, 4775 women). Oral misoprostol versus intravenous oxytocin (6 trials; 737 women, 200 with ruptured membranes) Misoprostol may make little or no difference to vaginal births within 24 hours (RR 1.12, 95% CI 0.95 to 1.33; 3 trials; 466 women; low-certainty evidence), but probably results in fewer caesarean sections (RR 0.67, 95% CI 0.50 to 0.90; 6 trials; 737 women; moderate-certainty evidence). The effect on hyperstimulation with foetal heart rate changes is uncertain (RR 0.66, 95% CI 0.19 to 2.26; 3 trials, 331 women; very low-certainty evidence). Oral misoprostol versus mechanical methods (6 trials; 2993 women) Six trials compared oral misoprostol to transcervical Foley catheter. Misoprostol may increase vaginal birth within 24 hours (RR 1.32, 95% CI 0.98 to 1.79; 4 trials; 1044 women; low-certainty evidence), and probably reduces the risk of caesarean section (RR 0.84, 95% CI 0.75 to 0.95; 6 trials; 2993 women; moderate-certainty evidence). There may be little or no difference in hyperstimulation with foetal heart rate changes (RR 1.31, 95% CI 0.78 to 2.21; 4 trials; 2828 women; low-certainty evidence). Oral misoprostol one- to two-hourly versus four- to six-hourly (1 trial; 64 women) The evidence on hourly titration was very uncertain due to the low numbers reported. Oral misoprostol 20 µg hourly titrated versus 25 µg two-hourly static (2 trials; 296 women) The difference in regimen may have little or no effect on the rate of vaginal births in 24 hours (RR 0.97, 95% CI 0.80 to 1.16; low-certainty evidence). The evidence is of very low certainty for all other reported outcomes.
AUTHORS' CONCLUSIONS
Low-dose oral misoprostol is probably associated with fewer caesarean sections (and therefore more vaginal births) than vaginal dinoprostone, and lower rates of hyperstimulation with foetal heart rate changes. However, time to birth may be increased, as seen by a reduced number of vaginal births within 24 hours. Compared to transcervical Foley catheter, low-dose oral misoprostol is associated with fewer caesarean sections, but equivalent rates of hyperstimulation. Low-dose misoprostol given orally rather than vaginally is probably associated with similar rates of vaginal birth, although rates may be lower within the first 24 hours. However, there is likely less hyperstimulation with foetal heart changes, and fewer caesarean sections performed due to foetal distress. The best available evidence suggests that low-dose oral misoprostol probably has many benefits over other methods for labour induction. This review supports the use of low-dose oral misoprostol for induction of labour, and demonstrates the lower risks of hyperstimulation than when misoprostol is given vaginally. More trials are needed to establish the optimum oral misoprostol regimen, but these findings suggest that a starting dose of 25 µg may offer a good balance of efficacy and safety.
Topics: Administration, Intravaginal; Administration, Oral; Apgar Score; Cesarean Section; Dinoprostone; Drug Administration Schedule; Female; Heart Rate, Fetal; Humans; Intensive Care, Neonatal; Labor, Induced; Misoprostol; Oxytocics; Oxytocin; Parturition; Placebos; Pregnancy; Randomized Controlled Trials as Topic; Time Factors; Uterus
PubMed: 34155622
DOI: 10.1002/14651858.CD014484