Interventions for supporting pregnant women's decision-making about mode of birth after a caesarean.

Pregnant women who have previously had a caesarean birth and who have no contraindication for vaginal birth after caesarean (VBAC) may need to decide whether to choose between a repeat caesarean birth or to commence labour with the intention of achieving a VBAC. Women need information about their options and interventions designed to support decision-making may be helpful. Decision support interventions can be implemented independently, or shared with health professionals during clinical encounters or used in mediated social encounters with others, such as telephone decision coaching services. Decision support interventions can include decision aids, one-on-one counselling, group information or support sessions and decision protocols or algorithms. This review considers any decision support intervention for pregnant women making birth choices after a previous caesarean birth. To examine the effectiveness of interventions to support decision-making about vaginal birth after a caesarean birth.Secondary objectives are to identify issues related to the acceptability of any interventions to parents and the feasibility of their implementation. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 June 2013), Current Controlled Trials (22 July 2013), the WHO International Clinical Trials Registry Platform Search Portal (ICTRP) (22 July 2013) and reference lists of retrieved articles. We also conducted citation searches of included studies to identify possible concurrent qualitative studies. All published, unpublished, and ongoing randomised controlled trials (RCTs) and quasi-randomised trials with reported data of any intervention designed to support pregnant women who have previously had a caesarean birth make decisions about their options for birth. Studies using a cluster-randomised design were eligible for inclusion but none were identified. Studies using a cross-over design were not eligible for inclusion. Studies published in abstract form only would have been eligible for inclusion if data were able to be extracted. Two review authors independently applied the selection criteria and carried out data extraction and quality assessment of studies. Data were checked for accuracy. We contacted authors of included trials for additional information. All included interventions were classified as independent, shared or mediated decision supports. Consensus was obtained for classifications. Verification of the final list of included studies was undertaken by three review authors. Three randomised controlled trials involving 2270 women from high-income countries were eligible for inclusion in the review. Outcomes were reported for 1280 infants in one study. The interventions assessed in the trials were designed to be used either independently by women or mediated through the involvement of independent support. No studies looked at shared decision supports, that is, interventions designed to facilitate shared decision-making with health professionals during clinical encounters.We found no difference in planned mode of birth: VBAC (risk ratio (RR) 1.03, 95% confidence interval (CI) 0.97 to 1.10; I² = 0%) or caesarean birth (RR 0.96, 95% CI 0.84 to 1.10; I² = 0%). The proportion of women unsure about preference did not change (RR 0.87, 95% CI 0.62 to 1.20; I² = 0%).There was no difference in adverse outcomes reported between intervention and control groups (one trial, 1275 women/1280 babies): permanent (RR 0.66, 95% CI 0.32 to 1.36); severe (RR 1.02, 95% CI 0.77 to 1.36); unclear (0.66, 95% CI 0.27, 1.61). Overall, 64.8% of those indicating preference for VBAC achieved it, while 97.1% of those planning caesarean birth achieved this mode of birth. We found no difference in the proportion of women achieving congruence between preferred and actual mode of birth (RR 1.02, 95% CI 0.96 to 1.07) (three trials, 1921 women).More women had caesarean births (57.3%), including 535 women where it was unplanned (42.6% all caesarean deliveries and 24.4% all births). We found no difference in actual mode of birth between groups, (average RR 0.97, 95% CI 0.89 to 1.06) (three trials, 2190 women).Decisional conflict about preferred mode of birth was lower (less uncertainty) for women with decisional support (standardised mean difference (SMD) -0.25, 95% CI -0.47 to -0.02; two trials, 787 women; I² = 48%). There was also a significant increase in knowledge among women with decision support compared with those in the control group (SMD 0.74, 95% CI 0.46 to 1.03; two trials, 787 women; I² = 65%). However, there was considerable heterogeneity between the two studies contributing to this outcome ( I² = 65%) and attrition was greater than 15 per cent and the evidence for this outcome is considered to be moderate quality only. There was no difference in satisfaction between women with decision support and those without it (SMD 0.06, 95% CI -0.09 to 0.20; two trials, 797 women; I² = 0%). No study assessed decisional regret or whether women's information needs were met.Qualitative data gathered in interviews with women and health professionals provided information about acceptability of the decision support and its feasibility of implementation. While women liked the decision support there was concern among health professionals about their impact on their time and workload. Evidence is limited to independent and mediated decision supports. Research is needed on shared decision support interventions for women considering mode of birth in a pregnancy after a caesarean birth to use with their care providers.

Horey D ，Kealy M ，Davey MA ，Small R ，Crowther CA ... -  《Cochrane Database of Systematic Reviews》

Antioxidants for female subfertility.

M.G. Showell, R. Mackenzie‐Proctor, V. Jordan, and R.J. Hart, “Antioxidants for Female Subfertility,” Cochrane Database of Systematic Reviews, no. 8 (2020): CD007807, https://doi.org/10.1002/14651858.CD007807.pub4 This Editorial Note is for the above article, published online on August 27, 2020, in Cochrane Library (cochranelibrary.com), and has been issued by the Publisher, John Wiley & Sons Ltd, in agreement with Cochrane. The Editorial note has been agreed due to concerns discovered by the Cochrane managing editor regarding the retraction of six studies in the Review (Badawy et al. 2006, 10.1016/j.fertnstert.2006.02.097; El Refaeey et al. 2014, 10.1016/j.rbmo.2014.03.011; El Sharkwy & Abd El Aziz 2019a, https://doi.org/10.1002/ijgo.12902; Gerli et al. 2007, https://doi.org/10.26355/eurrev_202309_33752, full text: https://europepmc.org/article/MED/18074942; Ismail et al. 2014, http://dx.doi.org/10.1016/j.ejogrb.2014.06.008; Hashemi et al. 2017, https://doi.org/10.1080/14767058.2017.1372413). In addition, expressions of concern have been published for two studies (Jamilian et al. 2018, https://doi.org/10.1007/s12011-017-1236-3; Zadeh Modarres 2018, https://doi.org/10.1007/s12011-017-1148-2). The retracted studies will be moved to the Excluded Studies table, and their impact on the review findings will be investigated and acted on accordingly in a future update. Initial checks indicate that removal of the six retracted studies did not make an appreciable difference to the results. Likewise, the studies for which Expressions of Concern were issued will be moved to the Awaiting classification table; they did not report any review outcomes, so removal will have no impact on the review findings. A couple may be considered to have fertility problems if they have been trying to conceive for over a year with no success. This may affect up to a quarter of all couples planning a child. It is estimated that for 40% to 50% of couples, subfertility may result from factors affecting women. Antioxidants are thought to reduce the oxidative stress brought on by these conditions. Currently, limited evidence suggests that antioxidants improve fertility, and trials have explored this area with varied results. This review assesses the evidence for the effectiveness of different antioxidants in female subfertility. To determine whether supplementary oral antioxidants compared with placebo, no treatment/standard treatment or another antioxidant improve fertility outcomes for subfertile women. We searched the following databases (from their inception to September 2019), with no language or date restriction: Cochrane Gynaecology and Fertility Group (CGFG) specialised register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL and AMED. We checked reference lists of relevant studies and searched the trial registers. We included randomised controlled trials (RCTs) that compared any type, dose or combination of oral antioxidant supplement with placebo, no treatment or treatment with another antioxidant, among women attending a reproductive clinic. We excluded trials comparing antioxidants with fertility drugs alone and trials that only included fertile women attending a fertility clinic because of male partner infertility. We used standard methodological procedures expected by Cochrane. The primary review outcome was live birth; secondary outcomes included clinical pregnancy rates and adverse events. We included 63 trials involving 7760 women. Investigators compared oral antioxidants, including: combinations of antioxidants, N-acetylcysteine, melatonin, L-arginine, myo-inositol, carnitine, selenium, vitamin E, vitamin B complex, vitamin C, vitamin D+calcium, CoQ10, and omega-3-polyunsaturated fatty acids versus placebo, no treatment/standard treatment or another antioxidant. Only 27 of the 63 included trials reported funding sources. Due to the very low-quality of the evidence we are uncertain whether antioxidants improve live birth rate compared with placebo or no treatment/standard treatment (odds ratio (OR) 1.81, 95% confidence interval (CI) 1.36 to 2.43; P < 0.001, I2 = 29%; 13 RCTs, 1227 women). This suggests that among subfertile women with an expected live birth rate of 19%, the rate among women using antioxidants would be between 24% and 36%. Low-quality evidence suggests that antioxidants may improve clinical pregnancy rate compared with placebo or no treatment/standard treatment (OR 1.65, 95% CI 1.43 to 1.89; P < 0.001, I2 = 63%; 35 RCTs, 5165 women). This suggests that among subfertile women with an expected clinical pregnancy rate of 19%, the rate among women using antioxidants would be between 25% and 30%. Heterogeneity was moderately high. Overall 28 trials reported on various adverse events in the meta-analysis. The evidence suggests that the use of antioxidants makes no difference between the groups in rates of miscarriage (OR 1.13, 95% CI 0.82 to 1.55; P = 0.46, I2 = 0%; 24 RCTs, 3229 women; low-quality evidence). There was also no evidence of a difference between the groups in rates of multiple pregnancy (OR 1.00, 95% CI 0.63 to 1.56; P = 0.99, I2 = 0%; 9 RCTs, 1886 women; low-quality evidence). There was also no evidence of a difference between the groups in rates of gastrointestinal disturbances (OR 1.55, 95% CI 0.47 to 5.10; P = 0.47, I2 = 0%; 3 RCTs, 343 women; low-quality evidence). Low-quality evidence showed that there was also no difference between the groups in rates of ectopic pregnancy (OR 1.40, 95% CI 0.27 to 7.20; P = 0.69, I2 = 0%; 4 RCTs, 404 women). In the antioxidant versus antioxidant comparison, low-quality evidence shows no difference in a lower dose of melatonin being associated with an increased live-birth rate compared with higher-dose melatonin (OR 0.94, 95% CI 0.41 to 2.15; P = 0.89, I2 = 0%; 2 RCTs, 140 women). This suggests that among subfertile women with an expected live-birth rate of 24%, the rate among women using a lower dose of melatonin compared to a higher dose would be between 12% and 40%. Similarly with clinical pregnancy, there was no evidence of a difference between the groups in rates between a lower and a higher dose of melatonin (OR 0.94, 95% CI 0.41 to 2.15; P = 0.89, I2 = 0%; 2 RCTs, 140 women). Three trials reported on miscarriage in the antioxidant versus antioxidant comparison (two used doses of melatonin and one compared N-acetylcysteine versus L-carnitine). There were no miscarriages in either melatonin trial. Multiple pregnancy and gastrointestinal disturbances were not reported, and ectopic pregnancy was reported by only one trial, with no events. The study comparing N-acetylcysteine with L-carnitine did not report live birth rate. Very low-quality evidence shows no evidence of a difference in clinical pregnancy (OR 0.81, 95% CI 0.33 to 2.00; 1 RCT, 164 women; low-quality evidence). Low quality evidence shows no difference in miscarriage (OR 1.54, 95% CI 0.42 to 5.67; 1 RCT, 164 women; low-quality evidence). The study did not report multiple pregnancy, gastrointestinal disturbances or ectopic pregnancy. The overall quality of evidence was limited by serious risk of bias associated with poor reporting of methods, imprecision and inconsistency. In this review, there was low- to very low-quality evidence to show that taking an antioxidant may benefit subfertile women. Overall, there is no evidence of increased risk of miscarriage, multiple births, gastrointestinal effects or ectopic pregnancies, but evidence was of very low quality. At this time, there is limited evidence in support of supplemental oral antioxidants for subfertile women.

Showell MG ，Mackenzie-Proctor R ，Jordan V ，Hart RJ ... -  《Cochrane Database of Systematic Reviews》

Antioxidants for female subfertility.

Showell MG ，Mackenzie-Proctor R ，Jordan V ，Hart RJ ... -  《Cochrane Database of Systematic Reviews》

Falls prevention interventions for community-dwelling older adults: systematic review and meta-analysis of benefits, harms, and patient values and preferences.

About 20-30% of older adults (≥ 65 years old) experience one or more falls each year, and falls are associated with substantial burden to the health care system, individuals, and families from resulting injuries, fractures, and reduced functioning and quality of life. Many interventions for preventing falls have been studied, and their effectiveness, factors relevant to their implementation, and patient preferences may determine which interventions to use in primary care. The aim of this set of reviews was to inform recommendations by the Canadian Task Force on Preventive Health Care (task force) on fall prevention interventions. We undertook three systematic reviews to address questions about the following: (i) the benefits and harms of interventions, (ii) how patients weigh the potential outcomes (outcome valuation), and (iii) patient preferences for different types of interventions, and their attributes, shown to offer benefit (intervention preferences). We searched four databases for benefits and harms (MEDLINE, Embase, AgeLine, CENTRAL, to August 25, 2023) and three for outcome valuation and intervention preferences (MEDLINE, PsycINFO, CINAHL, to June 9, 2023). For benefits and harms, we relied heavily on a previous review for studies published until 2016. We also searched trial registries, references of included studies, and recent reviews. Two reviewers independently screened studies. The population of interest was community-dwelling adults ≥ 65 years old. We did not limit eligibility by participant fall history. The task force rated several outcomes, decided on their eligibility, and provided input on the effect thresholds to apply for each outcome (fallers, falls, injurious fallers, fractures, hip fractures, functional status, health-related quality of life, long-term care admissions, adverse effects, serious adverse effects). For benefits and harms, we included a broad range of non-pharmacological interventions relevant to primary care. Although usual care was the main comparator of interest, we included studies comparing interventions head-to-head and conducted a network meta-analysis (NMAs) for each outcome, enabling analysis of interventions lacking direct comparisons to usual care. For benefits and harms, we included randomized controlled trials with a minimum 3-month follow-up and reporting on one of our fall outcomes (fallers, falls, injurious fallers); for the other questions, we preferred quantitative data but considered qualitative findings to fill gaps in evidence. No date limits were applied for benefits and harms, whereas for outcome valuation and intervention preferences we included studies published in 2000 or later. All data were extracted by one trained reviewer and verified for accuracy and completeness. For benefits and harms, we relied on the previous review team's risk-of-bias assessments for benefit outcomes, but otherwise, two reviewers independently assessed the risk of bias (within and across study). For the other questions, one reviewer verified another's assessments. Consensus was used, with adjudication by a lead author when necessary. A coding framework, modified from the ProFANE taxonomy, classified interventions and their attributes (e.g., supervision, delivery format, duration/intensity). For benefit outcomes, we employed random-effects NMA using a frequentist approach and a consistency model. Transitivity and coherence were assessed using meta-regressions and global and local coherence tests, as well as through graphical display and descriptive data on the composition of the nodes with respect to major pre-planned effect modifiers. We assessed heterogeneity using prediction intervals. For intervention-related adverse effects, we pooled proportions except for vitamin D for which we considered data in the control groups and undertook random-effects pairwise meta-analysis using a relative risk (any adverse effects) or risk difference (serious adverse effects). For outcome valuation, we pooled disutilities (representing the impact of a negative event, e.g. fall, on one's usual quality of life, with 0 = no impact and 1 = death and ~ 0.05 indicating important disutility) from the EQ-5D utility measurement using the inverse variance method and a random-effects model and explored heterogeneity. When studies only reported other data, we compared the findings with our main analysis. For intervention preferences, we used a coding schema identifying whether there were strong, clear, no, or variable preferences within, and then across, studies. We assessed the certainty of evidence for each outcome using CINeMA for benefit outcomes and GRADE for all other outcomes. A total of 290 studies were included across the reviews, with two studies included in multiple questions. For benefits and harms, we included 219 trials reporting on 167,864 participants and created 59 interventions (nodes). Transitivity and coherence were assessed as adequate. Across eight NMAs, the number of contributing trials ranged between 19 and 173, and the number of interventions ranged from 19 to 57. Approximately, half of the interventions in each network had at least low certainty for benefit. The fallers outcome had the highest number of interventions with moderate certainty for benefit (18/57). For the non-fall outcomes (fractures, hip fracture, long-term care [LTC] admission, functional status, health-related quality of life), many interventions had very low certainty evidence, often from lack of data. We prioritized findings from 21 interventions where there was moderate certainty for at least some benefit. Fourteen of these had a focus on exercise, the majority being supervised (for > 2 sessions) and of long duration (> 3 months), and with balance/resistance and group Tai Chi interventions generally having the most outcomes with at least low certainty for benefit. None of the interventions having moderate certainty evidence focused on walking. Whole-body vibration or home-hazard assessment (HHA) plus exercise provided to everyone showed moderate certainty for some benefit. No multifactorial intervention alone showed moderate certainty for any benefit. Six interventions only had very-low certainty evidence for the benefit outcomes. Two interventions had moderate certainty of harmful effects for at least one benefit outcome, though the populations across studies were at high risk for falls. Vitamin D and most single-component exercise interventions are probably associated with minimal adverse effects. Some uncertainty exists about possible adverse effects from other interventions. For outcome valuation, we included 44 studies of which 34 reported EQ-5D disutilities. Admission to long-term care had the highest disutility (1.0), but the evidence was rated as low certainty. Both fall-related hip (moderate certainty) and non-hip (low certainty) fracture may result in substantial disutility (0.53 and 0.57) in the first 3 months after injury. Disutility for both hip and non-hip fractures is probably lower 12 months after injury (0.16 and 0.19, with high and moderate certainty, respectively) compared to within the first 3 months. No study measured the disutility of an injurious fall. Fractures are probably more important than either falls (0.09 over 12 months) or functional status (0.12). Functional status may be somewhat more important than falls. For intervention preferences, 29 studies (9 qualitative) reported on 17 comparisons among single-component interventions showing benefit. Exercise interventions focusing on balance and/or resistance training appear to be clearly preferred over Tai Chi and other forms of exercise (e.g., yoga, aerobic). For exercise programs in general, there is probably variability among people in whether they prefer group or individual delivery, though there was high certainty that individual was preferred over group delivery of balance/resistance programs. Balance/resistance exercise may be preferred over education, though the evidence was low certainty. There was low certainty for a slight preference for education over cognitive-behavioral therapy, and group education may be preferred over individual education. To prevent falls among community-dwelling older adults, evidence is most certain for benefit, at least over 1-2 years, from supervised, long-duration balance/resistance and group Tai Chi interventions, whole-body vibration, high-intensity/dose education or cognitive-behavioral therapy, and interventions of comprehensive multifactorial assessment with targeted treatment plus HHA, HHA plus exercise, or education provided to everyone. Adding other interventions to exercise does not appear to substantially increase benefits. Overall, effects appear most applicable to those with elevated fall risk. Choice among effective interventions that are available may best depend on individual patient preferences, though when implementing new balance/resistance programs delivering individual over group sessions when feasible may be most acceptable. Data on more patient-important outcomes including fall-related fractures and adverse effects would be beneficial, as would studies focusing on equity-deserving populations and on programs delivered virtually. Not registered.

Pillay J ，Gaudet LA ，Saba S ，Vandermeer B ，Ashiq AR ，Wingert A ，Hartling L ... -  《Systematic Reviews》

Tranexamic acid for preventing postpartum haemorrhage after caesarean section.

Postpartum haemorrhage (PPH) is common and potentially life-threatening. The antifibrinolytic drug tranexamic acid (TXA) is recommended for treating PPH; it reduces the risk of death from haemorrhage by one-third when given soon after bleeding onset, but not overall risk of death. Interest in whether TXA may be effective in preventing PPH is growing. Evidence indicates that TXA given more than three hours after injury to bleeding trauma patients increases mortality. Potential harm becomes critical in prophylactic use of TXA. Reliable evidence of the effect and safety profile of TXA is required before widespread prophylactic use can be considered. To assess the effects of TXA for preventing PPH compared to placebo or no treatment (with or without uterotonic co-treatment) in women during caesarean birth. We searched CENTRAL, MEDLINE, Embase, and WHO ICTRP to 20 February 2024 and searched reference lists of retrieved studies. We included randomised controlled trials (RCTs) evaluating the use of TXA alone or plus uterotonics during caesarean birth for preventing PPH. Trials needed to be prospectively registered (i.e. before starting recruitment). We applied a trustworthiness checklist. The critical outcome was blood loss ≥ 1000 mL, measured using estimated or calculated methods. Important outcomes included maternal death, severe morbidity, blood transfusion, the use of additional surgical interventions to control PPH, thromboembolic events, use of additional uterotonics, hysterectomy, maternal satisfaction, and breastfeeding at discharge. We assessed risk of bias in the included studies using Cochrane's RoB 1 tool. Two review authors independently selected trials, extracted data, and assessed risk of bias and trial trustworthiness. We pooled data using random-effects meta-analysis. We assessed the certainty of the evidence using GRADE. We included six RCTs with 15,981 participants. All 12 trials in the previous version of this review were not included after review of trial registrations and trustworthiness checklists. Most included studies involved women at low risk of PPH and were conducted in high-resource settings. Prophylactic TXA in addition to standard care compared to placebo in addition to standard care or standard care alone TXA results in little to no difference in estimated blood loss ≥ 1000 mL (risk ratio (RR) 0.94, 95% confidence interval (CI) 0.79 to 1.11; 4 RCTs; n = 13,042; high certainty evidence), resulting in 8 fewer per 1000 women having estimated blood loss ≥ 1000 mL (from 30 fewer to 16 more). TXA likely results in a slight reduction in calculated blood loss ≥ 1000 mL (RR 0.83, 95% CI 0.76 to 0.92; 2 RCTs; n = 4327; moderate certainty evidence), resulting in 53 fewer per 1000 having calculated blood loss ≥ 1000 mL (from 75 fewer to 25 fewer). The evidence is very uncertain about the effect of TXA on maternal death (one event in placebo group, none in TXA group). No trials measured severe morbidity. TXA likely results in little to no difference in blood transfusion (RR 0.88, 95% CI 0.72 to 1.08; 5 RCTs; n = 15,740; moderate certainty evidence), resulting in 4 fewer per 1000 women requiring a blood transfusion (from 10 fewer to 3 more). TXA results in little to no difference in additional surgical interventions to control PPH (RR 1.02, 95% CI 0.86 to 1.22; 4 RCTs; n = 15,631; high certainty evidence), resulting in 1 more per 1000 women requiring additional surgical intervention (from 4 fewer to 7 more). The evidence is very uncertain about the effect of TXA on thromboembolic events (RR 1.40, 95% CI 0.22 to 8.90; 4 RCTs; n = 14,480; very low certainty evidence), resulting in 1 more per 1000 women having a thromboembolic event (from 2 fewer to 17 more). TXA results in little to no difference in the need for additional uterotonics (RR 0.88, 95% CI 0.78 to 1.00; 4 RCTs; n = 15,728; high certainty evidence), resulting in 15 fewer per 1000 women requiring additional uterotonics (from 27 fewer to 0 fewer). The evidence is very uncertain about the effect of TXA on hysterectomy (RR 0.80, 95% CI 0.20 to 3.29; 2 RCTs; n = 4546; very low certainty evidence), resulting in 3 fewer per 10,000 women requiring a hysterectomy (from 11 fewer to 31 more). One trial measuring maternal satisfaction reported no difference between groups at day two postpartum. No data were available on breastfeeding. Overall, studies had low risk of bias. We downgraded the certainty of evidence mainly for imprecision. Prophylactic TXA in addition to standard care during caesarean birth results in little to no difference in estimated blood loss ≥ 1000 mL and likely results in a slight reduction in calculated blood loss ≥ 1000 mL compared to placebo. There were no data for severe morbidity due to PPH. Event rates for further interventions to control PPH were low and similar across groups. Prophylactic TXA thus results in little to no difference between groups for additional surgical interventions (32 versus 31 per 1000), and likely results in little to no difference between groups for blood transfusions (31 versus 36 per 1000) and use of additional uterotonics (107 versus 121 per 1000). There were very few events for the outcomes maternal death (1 in placebo group), thromboembolic events (2 versus 3 per 1000), and hysterectomy (1 per 1000 in each group). Evidence for these serious adverse events is therefore very uncertain. Decisions about implementing routine prophylactic TXA during caesarean birth should not only consider outcomes related to blood loss, but also the relatively low rates of PPH morbidity and uncertainty of serious adverse events. Most studies included women at low risk of PPH, thereby precluding any conclusions about women at high risk of PPH. Cost associated with routine use of an additional drug for all caesarean births needs to be considered. This Cochrane review was funded in part by the World Health Organization. The published protocol and updates to the review can be accessed: Protocol (2009) DOI: 10.1002/14651858.CD007872 Original Review (2010) DOI: 10.1002/14651858.CD007872.pub2 Review Update (2015) DOI: 10.1002/14651858.CD007872.pub3.

Rohwer C ，Rohwer A ，Cluver C ，Ker K ，Hofmeyr GJ ... -  《Cochrane Database of Systematic Reviews》