-
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 -
Seminars in Arthritis and Rheumatism Aug 2021To assess how patient characteristics and study design influence the effectiveness of control interventions in hand OA trials. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To assess how patient characteristics and study design influence the effectiveness of control interventions in hand OA trials.
METHODS
The study protocol was registered in PROSPERO (CRD42020163473). Two authors independently searched four electronic databases from their inception to December 31, 2019. Randomized and non-randomized controlled hand OA trials were included if pain intensity was assessed using a validated scale. We allocated control groups into one of the following: placebo, add-on treatment, no treatment, or active treatment. The standardized mean differences (d) of pain, as well as subjective function and hand strength, were pooled with 95% confidence intervals (CI) and 90% prediction intervals using random-effects models. Meta-regression and post-hoc subgroup analyses were performed to investigate which factors potentially impacted placebo analgesia and between-study heterogeneity.
RESULTS
Thirty-one placebo, 11 add-on, 12 no-treatment, and 10 active-treatment controls were included in meta-analyses. Effective pain relief was observed in placebo (d = -0.50, 95% CI -0.63 to -0.37), add-on (d = -0.35, 95% CI -0.59 to -0.12), and active-treatment (d = -0.92, 95% CI -1.35 to -0.48) groups. In subjective function, these treatments had smaller but beneficial effects; hand strength, contrastingly, was not improved. Placebo effects were larger when flare designs were used (d = -0.96) and more homogeneous when minimum pain thresholds were set (d = -0.46, 90% prediction intervals -0.79 to -0.14).
CONCLUSION
Placebo, add-on, and active control treatments were more effective than the no treatment control in relieving hand pain and improving subjective function. By choosing minimum pain thresholds and flare requirements at patient enrollment, moderate pain relief may be replicated among control participants in future randomized placebo-controlled trials.
Topics: Control Groups; Hand; Humans; Osteoarthritis; Pain; Randomized Controlled Trials as Topic
PubMed: 34146952
DOI: 10.1016/j.semarthrit.2021.04.006 -
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 -
European Journal of Clinical... Jul 2022Randomized controlled trials (RCT) in mental disorders research commonly use active control groups including psychotherapeutic shams or inactive medication. This... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Randomized controlled trials (RCT) in mental disorders research commonly use active control groups including psychotherapeutic shams or inactive medication. This meta-analysis assessed whether placebo conditions (active controls) had an effect compared to no treatment or usual care (passive controls).
METHODS
PubMed, Scopus, PsycINFO, PsycARTICLES, Ovid, the Cochrane Central Register of Controlled Trials and Web of Science were searched from inception to April 2021 and reference lists of relevant articles. Three-arm RCTs, including active and passive control groups, were selected. Where individual standardized mean difference (SMD) was calculable, random effects meta-analyses were performed to estimate an overall effect size with 95% confidence intervals (CI) comparing active vs passive controls. Heterogeneity was assessed using I² statistic and meta-regression. Funnel asymmetry was evaluated using Egger's test (Prospero registration: CRD42021242940).
RESULTS
24 articles with 25 relevant RCTs were included in the review, of which 11 studies were of high risk of bias. There was an improvement in outcomes favouring the placebo conditions, compared to passive controls, overall (25 studies, SMD 0.24, 95% CI 0.06-0.42, I² = 43%) and in subgroups with anxiety (SMD 0.45, 95% CI 0.07-0.84, I² = 59%) or depression (SMD 0.22, 95% CI 0.04-0.39, I² = 0%). Meta-regression did not show a significant explanation for heterogeneity. Egger's test showed no asymmetry (p = .200).
CONCLUSIONS
A small placebo effect was observed in mental disorders research overall, and in patients with anxiety or depression. These findings should be interpreted with caution in the light of heterogeneity and risk of bias.
Topics: Anxiety; Humans; Mental Disorders; Placebo Effect
PubMed: 35224726
DOI: 10.1111/eci.13762 -
The Cochrane Database of Systematic... Apr 2020Cesarean delivery is one of the most common surgical procedures performed by obstetricians. Infectious morbidity after cesarean delivery can have a tremendous impact on... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cesarean delivery is one of the most common surgical procedures performed by obstetricians. Infectious morbidity after cesarean delivery can have a tremendous impact on the postpartum woman's return to normal function and her ability to care for her baby. Despite the widespread use of prophylactic antibiotics, postoperative infectious morbidity still complicates cesarean deliveries. This is an update of a Cochrane Review first published in 2010 and subsequently updated in 2012, twice in 2014, in 2017 and 2018.
OBJECTIVES
To determine if cleansing the vagina with an antiseptic solution before a cesarean delivery decreases the risk of maternal infectious morbidities, including endometritis and wound complications. We also assessed the side effects of vaginal cleansing solutions to determine adverse events associated with the intervention.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (7 July 2019), and reference lists of retrieved studies.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) and quasi-RCTs assessing the impact of vaginal cleansing immediately before cesarean delivery with any type of antiseptic solution versus a placebo solution/standard of care on post-cesarean infectious morbidity. Cluster-RCTs were eligible for inclusion, but we did not identify any. We excluded trials that utilized vaginal preparation during labor or that did not use antibiotic surgical prophylaxis. We also excluded any trials using a cross-over design. We included trials published in abstract form only if sufficient information was present in the abstract on methods and outcomes to analyze.
DATA COLLECTION AND ANALYSIS
At least three of the review authors independently assessed eligibility of the studies. Two review authors were assigned to extract study characteristics, quality assessments, and data from eligible studies.
MAIN RESULTS
We included 21 trials, reporting results for 7038 women evaluating the effects of vaginal cleansing (17 using povidone-iodine, 3 chlorhexidine, 1 benzalkonium chloride) on post-cesarean infectious morbidity. Trials used vaginal preparations administered by sponge sticks, douches, or soaked gauze wipes. The control groups were typically no vaginal preparation (17 trials) or the use of a saline vaginal preparation (4 trials). One trial did not report on any outcomes of interest. Trials were performed in 10 different countries (Saudi Arabia, Pakistan, Iran, Thailand, Turkey, USA, Egypt, UK, Kenya and India). The overall risk of bias was low for areas of attrition, reporting, and other bias. About half of the trials had low risk of selection bias, with most of the remainder rated as unclear. Due to lack of blinding, we rated performance bias as high risk in nearly one-third of the trials, low risk in one-third, and unclear in one-third. Vaginal preparation with antiseptic solution immediately before cesarean delivery probably reduces the incidence of post-cesarean endometritis from 7.1% in control groups to 3.1% in vaginal cleansing groups (average risk ratio (aRR) 0.41, 95% confidence interval (CI) 0.29 to 0.58; 20 trials, 6918 women; moderate-certainty evidence). This reduction in endometritis was seen for both iodine-based solutions and chlorhexidine-based solutions. Risks of postoperative fever and postoperative wound infection are also probably reduced by vaginal antiseptic preparation (fever: aRR 0.64, 0.50 to 0.82; 16 trials, 6163 women; and wound infection: RR 0.62, 95% CI 0.50 to 0.77; 18 trials, 6385 women; both moderate-certainty evidence). Two trials found that there may be a lower risk of a composite outcome of wound complication or endometritis in women receiving preoperative vaginal preparation (RR 0.46, 95% CI 0.26 to 0.82; 2 trials, 499 women; low-certainty evidence). No adverse effects were reported with either the povidone-iodine or chlorhexidine vaginal cleansing. Subgroup analysis suggested a greater effect with vaginal preparations for those women in labour versus those not in labour for four out of five outcomes examined (post-cesarean endometritis; postoperative fever; postoperative wound infection; composite wound complication or endometritis). This apparent difference needs to be investigated further in future trials. We did not observe any subgroup differences between women with ruptured membranes and women with intact membranes.
AUTHORS' CONCLUSIONS
Vaginal preparation with povidone-iodine or chlorhexidine solution compared to saline or not cleansing immediately before cesarean delivery probably reduces the risk of post-cesarean endometritis, postoperative fever, and postoperative wound infection. Subgroup analysis found that these benefits were typically present whether iodine-based or chlorhexidine-based solutions were used and when women were in labor before the cesarean. The suggested benefit in women in labor needs further investigation in future trials. There was moderate-certainty evidence using GRADE for all reported outcomes, with downgrading decisions based on limitations in study design or imprecision. As a simple intervention, providers may consider implementing preoperative vaginal cleansing with povidone-iodine or chlorhexidine before performing cesarean deliveries. Future research on this intervention being incorporated into bundles of care plans for women receiving cesarean delivery will be needed.
Topics: Administration, Intravaginal; Anti-Infective Agents, Local; Benzalkonium Compounds; Cesarean Section; Chlorhexidine; Disinfection; Endometritis; Female; Fever; Humans; Povidone-Iodine; Pregnancy; Preoperative Care; Randomized Controlled Trials as Topic; Surgical Wound Infection
PubMed: 32335895
DOI: 10.1002/14651858.CD007892.pub7 -
Obesity Reviews : An Official Journal... Feb 2024There is evidence that placebo and nocebo effects are significant for many conditions, but their impact on weight loss has not yet been well described. (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
There is evidence that placebo and nocebo effects are significant for many conditions, but their impact on weight loss has not yet been well described.
MATERIAL AND METHODS
A systematic review of studies indexed on PubMed, Cochrane, PsycINFO, PsycARTICLES, TripDatabase, and Embase was carried out. Studies (1) with at least two study groups - placebo and a corresponding control group; (2) published in English; and (3) focusing on adults participating in weight loss programs or on placebo/nocebo effects in weight loss were included. Synthesis and meta-analysis of the results of studies with comparable research plans were performed.
RESULTS
Some preliminary trends suggesting placebo and nocebo effects in weight loss were found. Placebo effects manifested in trends towards a slightly greater reduction of Body Mass Index (BMI) and body fat ratio in the placebo compared with the control groups. On the other hand, in one study, it was found that the expectancy effects of taking oral weight-loss agents might be disadvantageous (i.e., because they elicit a nocebo effect on weight loss).
CONCLUSION
The findings suggest a possibility that the nocebo effect may occur when an intervention has a medical context. In contrast, the placebo effect can be observed in cases where the intervention is of a different nature. However, considering the low number of studies analyzing the use of placebos in weight loss, new primary research is needed.
Topics: Adult; Humans; Nocebo Effect; Dietary Supplements; Research Design; Diet; Exercise
PubMed: 37950372
DOI: 10.1111/obr.13660 -
PloS One 2015Previous clinical trials indicate that probiotic consumption may improve blood glucose control, however, results from randomized trials on glycemic control have been... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Previous clinical trials indicate that probiotic consumption may improve blood glucose control, however, results from randomized trials on glycemic control have been inconsistent.
OBJECTIVE
To investigate the effects of probiotics on glycemic control in a systematic review and meta-analysis of randomized controlled trials.
DATA SOURCES
PubMed, Embase, Cochrane Library, and Clinicaltrial.gov through October 2014.
DATA EXTRACTION AND SYNTHESIS
Two independent reviewers extracted relevant data and assessed study quality and risk of bias. Data were pooled using a random-effects model and expressed as mean differences (MD) with 95% CI. Heterogeneity was assessed (Cochran Q-statistic) and quantified (I2).
RESULTS
Seventeen randomized controlled trials were included, in which 17 fasting blood glucose (n = 1105), 11 fasting plasma insulin (n = 788), 8 homeostasis model assessment of insulin resistance (n = 635) comparisons were reported. Probiotic consumption, compared with placebo, significantly reduced fasting glucose (MD = -0.31 mmol/L; 95% CI 0.56, 0.06; p = 0.02), fasting plasma insulin (MD = -1.29 μU/mL; 95% CI -2.17, -0.41; p = 0.004), and HOMA-IR (MD = 0.48; 95% CI -0.83, -0.13; p = 0.007).
CONCLUSIONS
Probiotic consumption may improve glycemic control modestly. Modification of gut microbiota by probiotic supplementation may be a method for preventing and control hyperglycemia in clinical practice.
Topics: Adolescent; Adult; Aged; Blood Glucose; Fasting; Female; Homeostasis; Humans; Hyperglycemia; Insulin; Insulin Resistance; Male; Middle Aged; Placebos; Probiotics; Publication Bias; Randomized Controlled Trials as Topic; Young Adult
PubMed: 26161741
DOI: 10.1371/journal.pone.0132121 -
The Cochrane Database of Systematic... Dec 2020The use of insulin-sensitising agents, such as metformin, in women with polycystic ovary syndrome (PCOS) who are undergoing ovulation induction or in vitro fertilisation... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The use of insulin-sensitising agents, such as metformin, in women with polycystic ovary syndrome (PCOS) who are undergoing ovulation induction or in vitro fertilisation (IVF) cycles has been widely studied. Metformin reduces hyperinsulinaemia and suppresses the excessive ovarian production of androgens. It is suggested that as a consequence metformin could improve assisted reproductive techniques (ART) outcomes, such as ovarian hyperstimulation syndrome (OHSS), pregnancy, and live birth rates.
OBJECTIVES
To determine the effectiveness and safety of metformin as a co-treatment during IVF or intracytoplasmic sperm injection (ICSI) in achieving pregnancy or live birth in women with PCOS.
SEARCH METHODS
We searched the Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL via the Cochrane Register of Studies Online (CRSO), MEDLINE, Embase, PsycINFO, LILACS, the trial registries for ongoing trials, and reference lists of articles (from inception to 13 February 2020).
SELECTION CRITERIA
Types of studies: randomised controlled trials (RCTs) comparing metformin treatment with placebo or no treatment in women with PCOS who underwent IVF or ICSI treatment.
TYPES OF PARTICIPANTS
women of reproductive age with anovulation due to PCOS with or without co-existing infertility factors. Types of interventions: metformin administered before and during IVF or ICSI treatment.
PRIMARY OUTCOME MEASURES
live birth rate, incidence of ovarian hyperstimulation syndrome.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected the studies, extracted the data according to the protocol, and assessed study quality. We assessed the overall quality of the evidence using the GRADE approach.
MAIN RESULTS
This updated review includes 13 RCTs involving a total of 1132 women with PCOS undergoing IVF/ICSI treatments. We stratified the analysis by type of ovarian stimulation protocol used (long gonadotrophin-releasing hormone agonist (GnRH-agonist) or short gonadotrophin-releasing hormone antagonist (GnRH-antagonist)) to determine whether the type of stimulation used influenced the outcomes. We did not perform meta-analysis on the overall (both ovarian stimulation protocols combined) data for the outcomes of live birth and clinical pregnancy rates per woman because of substantial heterogeneity. In the long protocol GnRH-agonist subgroup, the pooled evidence showed that we are uncertain of the effect of metformin on live birth rate per woman when compared with placebo/no treatment (risk ratio (RR) 1.30, 95% confidence interval (CI) 0.94 to 1.79; 6 RCTs; 651 women; I = 47%; low-quality evidence). This suggests that if the chance for live birth following placebo/no treatment is 28%, the chance following metformin would be between 27% and 51%. Only one study used short protocol GnRH-antagonist and reported live birth rate. Metformin may reduce live birth rate compared with placebo/no treatment (RR 0.48, 95% CI 0.29 to 0.79; 1 RCT; 153 women; low-quality evidence). This suggests that if the chance for live birth following placebo/no treatment is 43%, the chance following metformin would be between 13% and 34% (short GnRH-antagonist protocol). We found that metformin may reduce the incidence of OHSS (RR 0.46, 95% CI 0.29 to 0.72; 11 RCTs; 1091 women; I = 38%; low-quality evidence). This suggests that for a woman with a 20% risk of OHSS without metformin, the corresponding risk using metformin would be between 6% and 14%. Using long protocol GnRH-agonist stimulation, metformin may increase clinical pregnancy rate per woman compared with placebo/no treatment (RR 1.32, 95% CI 1.08 to 1.63; 10 RCTs; 915 women; I = 13%; low-quality evidence). Using short protocol GnRH-antagonist, we are uncertain of the effect of metformin on clinical pregnancy rate per woman compared with placebo/no treatment (RR 1.38, 95% CI 0.21 to 9.14; 2 RCTs; 177 women; I = 87%; very low-quality evidence). We are uncertain of the effect of metformin on miscarriage rate per woman when compared with placebo/no treatment (RR 0.86, 95% CI 0.56 to 1.32; 8 RCTs; 821 women; I = 0%; low-quality evidence). Metformin may result in an increase in side effects compared with placebo/no treatment (RR 3.35, 95% CI 2.34 to 4.79; 8 RCTs; 748 women; I = 0%; low-quality evidence). The overall quality of evidence ranged from very low to low. The main limitations were inconsistency, risk of bias, and imprecision.
AUTHORS' CONCLUSIONS
This updated review on metformin versus placebo/no treatment before or during IVF/ICSI treatment in women with PCOS found no conclusive evidence that metformin improves live birth rates. In a long GnRH-agonist protocol, we are uncertain whether metformin improves live birth rates, but metformin may increase the clinical pregnancy rate. In a short GnRH-antagonist protocol, metformin may reduce live birth rates, although we are uncertain about the effect of metformin on clinical pregnancy rate. Metformin may reduce the incidence of OHSS but may result in a higher incidence of side effects. We are uncertain of the effect of metformin on miscarriage rate per woman.
Topics: Abortion, Spontaneous; Bias; Confidence Intervals; Female; Fertilization in Vitro; Humans; Hyperandrogenism; Hyperinsulinism; Hypoglycemic Agents; Live Birth; Metformin; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Placebos; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate; Randomized Controlled Trials as Topic; Sperm Injections, Intracytoplasmic
PubMed: 33347618
DOI: 10.1002/14651858.CD006105.pub4 -
European Journal of Clinical... Nov 2019Poorly described placebo/sham controls make it difficult to appraise active intervention benefits and harms. The 12-item Template for Intervention Description and...
BACKGROUND
Poorly described placebo/sham controls make it difficult to appraise active intervention benefits and harms. The 12-item Template for Intervention Description and Replication (TIDieR) checklist was developed to improve the reporting of active interventions. The extent to which TIDieR has been used to improve description of placebo or sham control is not known.
MATERIALS AND METHODS
We systematically identified and examined all placebo/sham-controlled randomised trials published in 2018 in the top six general medical journals. We reported how many of the TIDieR checklist items were used to describe the placebo/sham control(s). We supplemented this with a sample of 100 placebo/sham-controlled trials from any journal and searched Google Scholar to identify placebo/sham-controlled trials citing TIDieR.
RESULTS
We identified 94 placebo/sham-controlled trials published in the top journals in 2018. None reported using TIDieR, and none reported placebo or sham components completely. On average eight TIDieR items were addressed, with placebo/sham control name (100%) and when and how much was administered (97.9%) most commonly reported. Some items (rationale, 8.5%, whether there were modifications, 25.5%) were less often reported. In our sample of less well-cited journals, reporting was poorer (average of six items) and followed a similar pattern. Since TIDieR's first publication, six placebo-controlled trials have cited it according to Google Scholar. Two of these used the checklist to describe placebo controls; neither one completely desribed the placebo intervention.
CONCLUSIONS
Placebo and sham controls are poorly described within randomised trials, and TIDieR is rarely used to guide these descriptions. We recommend developing guidelines to promote better descriptions of placebo/sham control components within clinical trials.
Topics: Checklist; Control Groups; Humans; Placebos; Randomized Controlled Trials as Topic; Research Report
PubMed: 31519047
DOI: 10.1111/eci.13169 -
PloS One 2016There are few drugs with proven efficacy in cutaneous leishmaniasis (CL), and pentavalent antimonial derivatives are still the main first-line therapeutic agents... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
There are few drugs with proven efficacy in cutaneous leishmaniasis (CL), and pentavalent antimonial derivatives are still the main first-line therapeutic agents worldwide, despite their recognized high toxicities. Randomized controlled clinical trials assessing the efficacy and safety of new therapeutic modalities are of high priority, and the definition of the design of such trials raises debate about the use of placebo as a comparator. To support the use of placebo as a comparator, two main points need to be addressed: 1--the cure rate without any therapeutic intervention and 2--the damage caused by CL and its impact on patients.
OBJECTIVE
The aim of this study was to systematically assess the spontaneous cure rate for American CL and to broaden the discussion about placebo use in CL trials.
METHODS
The PRISMA guidelines for systematic reviews and the Cochrane manual were followed. The sources used were the PubMed and LILACS databases. Studies were included if they reported cure rates using placebo or no treatment in American CL.
RESULTS
Thirteen studies of a total of 352 patients were ultimately included in this review. The summarized global cure rates for all Leishmania species according to the intention-to-treat analyses performed at approximately three ("initial cure") and nine ("definitive cure") months after "no treatment" or placebo use were 26% (CI95%: 16 to 40%) and 26% (CI95%:16 to 38%), respectively. Notably, a significantly lower cure rate was observed for L. braziliensis infection (6.4%, CI95%:0.2 to 20%) than for L. mexicana infection (44%, CI95%:19 to 72%), p = 0.002. Of note, relapse occurred in 20% of patients with initial healing (CI95%:9.2 to 38.9%).
CONCLUSION
These results clearly demonstrate a low spontaneous cure rate following no-treatment or placebo use, confirming that this strategy for the control group in CL studies expose patients to greater morbidity, especially for CL caused by L. braziliensis. Therefore, from this point, the crucial question to consider regarding placebo use is the seriousness of the suffering caused by this disease.
Topics: Antiprotozoal Agents; Humans; Leishmaniasis, Cutaneous; Placebos; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 26894430
DOI: 10.1371/journal.pone.0149697