Summary Background Screening for congenital heart defects relies on antenatal ultrasonography and postnatal clinical examination; however, life-threatening defects often are not detected. We ...prospectively assessed the accuracy of pulse oximetry as a screening test for congenital heart defects. Methods In six maternity units in the UK, asymptomatic newborn babies (gestation >34 weeks) were screened with pulse oximetry before discharge. Infants who did not achieve predetermined oxygen saturation thresholds underwent echocardiography. All other infants were followed up to 12 months of age by use of regional and national registries and clinical follow-up. The main outcome was the sensitivity and specificity of pulse oximetry for detection of critical congenital heart defects (causing death or requiring invasive intervention before 28 days) or major congenital heart disease (causing death or requiring invasive intervention within 12 months of age). Findings 20 055 newborn babies were screened and 53 had major congenital heart disease (24 critical), a prevalence of 2·6 per 1000 livebirths. Analyses were done on all babies for whom a pulse oximetry reading was obtained. Sensitivity of pulse oximetry was 75·00% (95% CI 53·29–90·23) for critical cases and 49·06% (35·06–63·16) for all major congenital heart defects. In 35 cases, congenital heart defects were already suspected after antenatal ultrasonography, and exclusion of these reduced the sensitivity to 58·33% (27·67–84·83) for critical cases and 28·57% (14·64–46·30) for all cases of major congenital heart defects. False-positive results were noted for 169 (0·8%) babies (specificity 99·16%, 99·02–99·28), of which six cases were significant, but not major, congenital heart defects, and 40 were other illnesses that required urgent medical intervention. Interpretation Pulse oximetry is a safe, feasible test that adds value to existing screening. It identifies cases of critical congenital heart defects that go undetected with antenatal ultrasonography. The early detection of other diseases is an additional advantage. Funding National Institute for Health Research Health Technology Assessment programme.
Metformin for endometrial hyperplasia Shiwani, Hunain; Shiwani, Hunain; Clement, Naomi S ...
Cochrane database of systematic reviews,
05/2024, Letnik:
2024, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Background
Endometrial cancer is one of the most common gynaecological cancers in the world. Rates of endometrial cancer are rising, in part because of rising obesity rates. Endometrial hyperplasia ...is a precancerous condition in women that can lead to endometrial cancer if left untreated. Endometrial hyperplasia occurs more commonly than endometrial cancer. Progesterone tablets that are currently used to treat women with endometrial hyperplasia are associated with adverse effects in up to 84% of women. A levonorgestrel intrauterine device may improve compliance, but it is invasive, is not acceptable to all women, and is associated with irregular vaginal bleeding in 82% of cases. Therefore, an alternative treatment for women with endometrial hyperplasia is needed.
Metformin, a drug that is often used to treat people with diabetes, has been shown, in some human studies, to reverse endometrial hyperplasia. However, the effectiveness and safety of metformin for treatment of endometrial hyperplasia remain uncertain. This is an update of a review first published in 2017.
Objectives
To determine the effectiveness and safety of metformin in treating women with endometrial hyperplasia.
Search methods
We searched the Cochrane Gynaecology and Fertility Specialised Register, CENTRAL, MEDLINE, PubMed, Embase, Google Scholar, OpenGrey, LILACS, and two trials registers from inception to 5 September 2022. We searched the bibliographies of all relevant studies, and contacted experts in the field for any additional trials.
Selection criteria
We included randomised controlled trials (RCTs) and cross‐over trials comparing metformin (used alone or in combination with other medical therapies) versus placebo, no treatment, any conventional medical treatment, or any other active intervention for women with histologically confirmed endometrial hyperplasia of any type.
Data collection and analysis
Two review authors independently assessed studies for eligibility, extracted data from included studies, assessed the risk of bias in the included studies, and assessed the certainty of the evidence for each outcome. We resolved disagreements by discussion or by deferring to a third review author. When study details were missing, review authors contacted the study authors. The primary outcome of this review was regression of endometrial hyperplasia histology (with or without atypia) towards normal histology.
Main results
We included seven RCTs, in which a total of 387 women took part. In the comparison, Metformin plus megestrol versus megestrol alone, we rated the certainty of the evidence as low for the outcome, regression of endometrial hyperplasia. We rated the quality of the evidence as very low for the rest of the outcomes, in all three comparisons.
Although there was a low risk of selection bias, there was a high risk of bias in the blinding of personnel and outcome assessment (performance bias and detection bias) in many studies. This update identified four new RCTs and six ongoing RCTs.
Metformin versus megestrol
We are uncertain whether metformin increases the regression of endometrial hyperplasia towards normal histology over megestrol (odds ratio (OR) 4.89, 95% confidence interval (CI) 1.56 to 15.32; P = 0.006; 2 RCTs, 83 participants; I² = 7%; very low‐certainty evidence). This evidence suggests that if the rate of regression with megestrol is 61%, the rate of regression with metformin would be between 71% and 96%.
It is unresolved whether metformin results in different rates of abnormal uterine bleeding or hysterectomy compared to megestrol.
No study in this comparison reported progression of hyperplasia to endometrial cancer, recurrence of endometrial hyperplasia, health‐related quality of life, or adverse effects during treatment.
Metformin plus megestrol versus megestrol monotherapy
The combination of metformin and megestrol may enhance the regression of endometrial hyperplasia towards normal histology more than megestrol alone (OR 3.27, 95% CI 1.65 to 6.51; P = 0.0007; 4 RCTs, 258 participants; I² = 0%, low‐certainty evidence). This suggests that if the rate of regression with megestrol monotherapy is 54%, the rate of regression with the addition of metformin would be between 66% and 84%.
In one study, 3/8 (37.5%) of participants who took metformin had nausea that settled without further treatment.
It is unresolved whether the combination of metformin and megestrol results in different rates of recurrence of endometrial hyperplasia, progression of endometrial hyperplasia to endometrial cancer, or hysterectomy compared to megestrol monotherapy.
No study in this comparison reported abnormal uterine bleeding, or health‐related quality of life.
Metformin plus levonorgestrel (intrauterine system) versus levonorgestrel (intrauterine system) monotherapy
We are uncertain whether there is a difference between groups in the regression of endometrial hyperplasia towards normal histology (OR 0.29, 95% CI 0.01 to 7.56; 1 RCT, 46 participants; very low‐certainty evidence). This evidence suggests that if the rate of regression with levonorgestrel monotherapy is 96%, the rate of regression with the addition of metformin would be between 73% and 100%.
It is unresolved whether the combination of metformin and levonorgestrel results in different rates of abnormal uterine bleeding, hysterectomy, or the development of adverse effects during treatment compared to levonorgestrel monotherapy.
No study in this comparison reported recurrence of endometrial hyperplasia, progression of hyperplasia to endometrial cancer, or health‐related quality of life.
Authors' conclusions
Review authors found insufficient evidence to either support or refute the use of metformin, specifically megestrol acetate, given alone or in combination with standard therapy, for the treatment of women with endometrial hyperplasia.
Robustly designed and adequately powered randomised controlled trials, yielding long‐term outcome data are still needed to address this clinical question.
Summary Background Fetal lower urinary tract obstruction (LUTO) is associated with high perinatal and long-term childhood mortality and morbidity. We aimed to assess the effectiveness of ...vesicoamniotic shunting for treatment of LUTO. Methods In a randomised trial in the UK, Ireland, and the Netherlands, women whose pregnancies with a male fetus were complicated by isolated LUTO were randomly assigned by a central telephone and web-based randomisation service to receive either the intervention (placement of vesicoamniotic shunt) or conservative management. Allocation could not be masked from clinicians or participants because of the invasive nature of the intervention. Diagnosis was by prenatal ultrasound. The primary outcome was survival of the baby to 28 days postnatally. All primary analyses were done on an intention-to-treat basis, but these results were compared with those of an as-treated analysis to investigate the effect of a fairly large proportion of crossovers. We used Bayesian methods to estimate the posterior probability distribution of the effectiveness of vesicoamniotic shunting at 28 days. The study is registered with the ISRCTN Register, number ISRCTN53328556. Findings 31 women with singleton pregnancies complicated by LUTO were included in the trial and main analysis, with 16 allocated to the vesicoamniotic shunt group and 15 to the conservative management group. The study closed early because of poor recruitment. There were 12 livebirths in each group. In the vesicoamniotic shunt group one intrauterine death occurred and three pregnancies were terminated. In the conservative management group one intrauterine death occurred and two pregnancies were terminated. Of the 16 pregnancies randomly assigned to vesicoamniotic shunting, eight neonates survived to 28 days, compared with four from the 15 pregnancies assigned to conservative management (intention-to-treat relative risk RR 1·88, 95% CI 0·71–4·96; p=0·27). Analysis based on treatment received showed a larger effect (3·20, 1·06–9·62; p=0·03). All 12 deaths were caused by pulmonary hypoplasia in the early neonatal period. Sensitivity analysis in which non-treatment-related terminations of pregnancy were excluded made some slight changes to point estimates only. Bayesian analysis in which the trial data were combined with elicited priors from experts suggested an 86% probability that vesicoamniotic shunting increased survival at 28 days and a 25% probability that it had a large, clinically important effect (defined as a relative increase of 55% or more in the proportion of neonates who survived). There was substantial short-term and long-term morbidity in both groups, including poor renal function—only two babies (both in the shunt group) survived to 2 years with normal renal function. Seven complications occurred in six fetuses from the shunt group, including spontaneous ruptured membranes, shunt blockage, and dislodgement. These complications resulted in four pregnancy losses. Interpretation Survival seemed to be higher in the fetuses receiving vesicoamniotic shunting, but the size and direction of the effect remained uncertain, such that benefit could not be conclusively proven. Our results suggest that the chance of newborn babies surviving with normal renal function is very low irrespective of whether or not vesicoamniotic shunting is done. Funding UK National Institute of Health Research, Wellbeing of Women, Hannah Eliza Guy Charity (Birmingham Children's Hospital Charity).
In this multicenter, randomized, open-label trial that compared myomectomy with uterine-artery embolization in women who had symptomatic uterine fibroids and wanted to avoid hysterectomy, myomectomy ...resulted in a better fibroid-related quality of life at 2 years than uterine-artery embolization.
Pelvic venous disorders (PeVDs) in women can present with chronic pelvic pain, lower-extremity and vulvar varicosities, lower-extremity swelling and pain, and left-flank pain and hematuria. Multiple ...evidence gaps exist related to PeVDs with the consequence that nonvascular specialists rarely consider the diagnosis. Recognizing this, the Society of Interventional Radiology Foundation funded a Research Consensus Panel to prioritize a research agenda to address these gaps. This paper presents the proceedings and recommendations from that Panel.
In this multicenter, randomized, double-blind, placebo-controlled trial involving women with vaginal bleeding in early pregnancy, treatment with progesterone during the first trimester did not result ...in a significantly higher incidence of live births than placebo.
Excessive haemorrhage at cesarean section requires donor (allogeneic) blood transfusion. Cell salvage may reduce this requirement.
We conducted a pragmatic randomised controlled trial (at 26 ...obstetric units; participants recruited from 4 June 2013 to 17 April 2016) of routine cell salvage use (intervention) versus current standard of care without routine salvage use (control) in cesarean section among women at risk of haemorrhage. Randomisation was stratified, using random permuted blocks of variable sizes. In an intention-to-treat analysis, we used multivariable models, adjusting for stratification variables and prognostic factors identified a priori, to compare rates of donor blood transfusion (primary outcome) and fetomaternal haemorrhage ≥2 ml in RhD-negative women with RhD-positive babies (a secondary outcome) between groups. Among 3,028 women randomised (2,990 analysed), 95.6% of 1,498 assigned to intervention had cell salvage deployed (50.8% had salvaged blood returned; mean 259.9 ml) versus 3.9% of 1,492 assigned to control. Donor blood transfusion rate was 3.5% in the control group versus 2.5% in the intervention group (adjusted odds ratio OR 0.65, 95% confidence interval CI 0.42 to 1.01, p = 0.056; adjusted risk difference -1.03, 95% CI -2.13 to 0.06). In a planned subgroup analysis, the transfusion rate was 4.6% in women assigned to control versus 3.0% in the intervention group among emergency cesareans (adjusted OR 0.58, 95% CI 0.34 to 0.99), whereas it was 2.2% versus 1.8% among elective cesareans (adjusted OR 0.83, 95% CI 0.38 to 1.83) (interaction p = 0.46). No case of amniotic fluid embolism was observed. The rate of fetomaternal haemorrhage was higher with the intervention (10.5% in the control group versus 25.6% in the intervention group, adjusted OR 5.63, 95% CI 1.43 to 22.14, p = 0.013). We are unable to comment on long-term antibody sensitisation effects.
The overall reduction observed in donor blood transfusion associated with the routine use of cell salvage during cesarean section was not statistically significant.
This trial was prospectively registered on ISRCTN as trial number 66118656 and can be viewed on http://www.isrctn.com/ISRCTN66118656.
Pelvic congestion syndrome (PCS) is described as chronic pelvic pain (CPP) arising from dilated and refluxing pelvic veins, although the causal relationship between pelvic vein incompetence (PVI) and ...CPP is not established. Non-invasive screening methods such as Doppler ultrasound and magnetic resonance venography are used before confirmation by venography. Percutaneous embolisation has become the principal treatment for PCS, with high success rates often cited.
Our proposal aimed to systematically and critically review the definitions and diagnostic criteria of PCS, the association between PVI and CPP, the accuracy of various non-invasive imaging techniques and the effectiveness of embolisation for PVI; and to identify factors associated with successful outcome. We also wished to survey clinicians and patients to assess awareness and management of PCS and gauge the enthusiasm for further research.
A comprehensive search strategy encompassing various terms for pelvic congestion, pain, imaging techniques and embolisation was deployed in 17 bibliographic databases, including MEDLINE, EMBASE and Web of Science. There was no restriction on study design.
Methodological quality was assessed using appropriate tools. Online surveys were sent to clinicians and patients. The quality and heterogeneity generally precluded meta-analysis and so results were tabulated and described narratively.
We identified six association studies, 10 studies involving ultrasound, two studies involving magnetic resonance venography, 21 case series and one poor-quality randomised trial of embolisation. There were no consistent diagnostic criteria for PCS. We found that the associations between CPP and PVI were generally fairly similar, with three of five studies with sufficient data showing statistically significant associations (odds ratios of between 31 and 117). The prevalence of PVI ranged widely, although the majority of women with PVI had CPP. Transvaginal ultrasound with Doppler and magnetic resonance venography are both useful screening methods, although the data on accuracy are limited. Early substantial relief from pain symptoms was observed in approximately 75% of women undergoing embolisation, a figure which generally increased over time and was sustained. Reintervention rates were generally low. Transient pain was a common occurrence following foam embolisation, while there was a < 2% risk of coil migration. Confidence in the embolisation technique is reasonably high, although there is a desire to strengthen the evidence base. Even among women with CPP, fewer than half had any knowledge about PCS.
The data supporting the diagnosis and treatment of PCS are limited and of variable methodological quality. There is some evidence to tentatively support a causative association, but it cannot be categorically stated that PVI is the cause of CPP in women with no other pathology, as the six most pertinent drew on clinically disparate populations and defined PVI inconsistently. Embolisation appears to provide symptomatic relief in the majority of women and is safe. However, the majority of included studies of embolism were relatively small case series and only the randomised controlled trial was considered at risk of potential biases. There is scope and demand for considerable further research. The question of the association of PVI and CPP requires a well-designed and well-powered case-control study, which will also provide data to derive a diagnostic standard. An adequately powered randomised trial is essential to provide evidence on the effectiveness of embolisation, but this faces methodological challenges.
This study is registered as PROSPERO CRD42012002237 and CRD42012002238.
The National Institute for Health Research Health Technology Assessment programme.
Testing for group B streptococcus (GBS) requires a vaginal-rectal swab in late pregnancy.
A systematic review of the test accuracy of a self-collected swab compared with a health-care professional ...collected swab in the diagnosis of GBS colonisation.
The Cochrane Library (including the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects DARE and the Cochrane Central Register of Controlled Trials CENTRAL), EMBASE, MEDLINE and Trip were searched in May 2022.
Randomised trials, test accuracy studies or diagnostic yield studies that compared the accuracy of a self-collected vaginal-rectal swab, compared to that taken by a health-care professional, for the detection of GBS colonisation in the third trimester.
Two researchers independently screened, selected studies, extracted data and assessed study quality.
10 studies, with 2578 women were included. Pooled sensitivity of self-collected swabs was 0.90 (95% confidence interval CI 0.81 to 0.95) and pooled specificity was 0.98 (95% CI 0.96 to 0.99).
This study provides reassuring evidence that self-collected swabs for maternal GBS colonisation are highly accurate relative to swabs collected by health-care professionals. Women requiring a swab for GBS colonisation can self-swab with appropriate instructions if they choose.
Personal fellowship from the University of Nottingham for KFW.
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