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Lancet (London, England) May 2017Corrosive ingestion is a rare but potentially devastating event and, despite the availability of effective preventive public health strategies, injuries continue to... (Review)
Review
Corrosive ingestion is a rare but potentially devastating event and, despite the availability of effective preventive public health strategies, injuries continue to occur. Most clinicians have limited personal experience and rely on guidelines; however, uncertainty persists about best clinical practice. Ingestions range from mild cases with no injury to severe cases with full thickness necrosis of the oesophagus and stomach. CT scan is superior to traditional endoscopy for stratification of patients to emergency resection or observation. Oesophageal stricture is a common consequence of ingestion and newer stents show some promise; however, the place of endoscopic stenting for corrosive strictures is yet to be defined. We summarise the evidence to provide a plan for managing these potentially life-threatening injuries and discuss the areas where further research is required to improve outcomes.
Topics: Burns, Chemical; Caustics; Digestive System Surgical Procedures; Disease Management; Esophageal Stenosis; Humans; Practice Guidelines as Topic; Stomach; Tomography, X-Ray Computed; Treatment Outcome; Watchful Waiting
PubMed: 28045663
DOI: 10.1016/S0140-6736(16)30313-0 -
The New England Journal of Medicine Mar 2023Cyclooxygenase inhibitors are commonly used in infants with patent ductus arteriosus (PDA), but the benefit of these drugs is uncertain. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Cyclooxygenase inhibitors are commonly used in infants with patent ductus arteriosus (PDA), but the benefit of these drugs is uncertain.
METHODS
In this multicenter, noninferiority trial, we randomly assigned infants with echocardiographically confirmed PDA (diameter, >1.5 mm, with left-to-right shunting) who were extremely preterm (<28 weeks' gestational age) to receive either expectant management or early ibuprofen treatment. The composite primary outcome included necrotizing enterocolitis (Bell's stage IIa or higher), moderate to severe bronchopulmonary dysplasia, or death at 36 weeks' postmenstrual age. The noninferiority of expectant management as compared with early ibuprofen treatment was defined as an absolute risk difference with an upper boundary of the one-sided 95% confidence interval of less than 10 percentage points.
RESULTS
A total of 273 infants underwent randomization. The median gestational age was 26 weeks, and the median birth weight was 845 g. A primary-outcome event occurred in 63 of 136 infants (46.3%) in the expectant-management group and in 87 of 137 (63.5%) in the early-ibuprofen group (absolute risk difference, -17.2 percentage points; upper boundary of the one-sided 95% confidence interval [CI], -7.4; P<0.001 for noninferiority). Necrotizing enterocolitis occurred in 24 of 136 infants (17.6%) in the expectant-management group and in 21 of 137 (15.3%) in the early-ibuprofen group (absolute risk difference, 2.3 percentage points; two-sided 95% CI, -6.5 to 11.1); bronchopulmonary dysplasia occurred in 39 of 117 infants (33.3%) and in 57 of 112 (50.9%), respectively (absolute risk difference, -17.6 percentage points; two-sided 95% CI, -30.2 to -5.0). Death occurred in 19 of 136 infants (14.0%) and in 25 of 137 (18.2%), respectively (absolute risk difference, -4.3 percentage points; two-sided 95% CI, -13.0 to 4.4). Rates of other adverse outcomes were similar in the two groups.
CONCLUSIONS
Expectant management for PDA in extremely premature infants was noninferior to early ibuprofen treatment with respect to necrotizing enterocolitis, bronchopulmonary dysplasia, or death at 36 weeks' postmenstrual age. (Funded by the Netherlands Organization for Health Research and Development and the Belgian Health Care Knowledge Center; BeNeDuctus ClinicalTrials.gov number, NCT02884219; EudraCT number, 2017-001376-28.).
Topics: Humans; Infant; Infant, Newborn; Bronchopulmonary Dysplasia; Ductus Arteriosus, Patent; Echocardiography; Enterocolitis, Necrotizing; Ibuprofen; Indomethacin; Infant, Extremely Premature; Infant, Low Birth Weight; Infant, Newborn, Diseases; Watchful Waiting
PubMed: 36477458
DOI: 10.1056/NEJMoa2207418 -
Otolaryngology--head and Neck Surgery :... Apr 2015This update of a 2007 guideline from the American Academy of Otolaryngology--Head and Neck Surgery Foundation provides evidence-based recommendations to manage adult...
OBJECTIVE
This update of a 2007 guideline from the American Academy of Otolaryngology--Head and Neck Surgery Foundation provides evidence-based recommendations to manage adult rhinosinusitis, defined as symptomatic inflammation of the paranasal sinuses and nasal cavity. Changes from the prior guideline include a consumer added to the update group, evidence from 42 new systematic reviews, enhanced information on patient education and counseling, a new algorithm to clarify action statement relationships, expanded opportunities for watchful waiting (without antibiotic therapy) as initial therapy of acute bacterial rhinosinusitis (ABRS), and 3 new recommendations for managing chronic rhinosinusitis (CRS).
PURPOSE
The purpose of this multidisciplinary guideline is to identify quality improvement opportunities in managing adult rhinosinusitis and to create explicit and actionable recommendations to implement these opportunities in clinical practice. Specifically, the goals are to improve diagnostic accuracy for adult rhinosinusitis, promote appropriate use of ancillary tests to confirm diagnosis and guide management, and promote judicious use of systemic and topical therapy, which includes radiography, nasal endoscopy, computed tomography, and testing for allergy and immune function. Emphasis was also placed on identifying multiple chronic conditions that would modify management of rhinosinusitis, including asthma, cystic fibrosis, immunocompromised state, and ciliary dyskinesia.
ACTION STATEMENTS
The update group made strong recommendations that clinicians (1) should distinguish presumed ABRS from acute rhinosinusitis (ARS) caused by viral upper respiratory infections and noninfectious conditions and (2) should confirm a clinical diagnosis of CRS with objective documentation of sinonasal inflammation, which may be accomplished using anterior rhinoscopy, nasal endoscopy, or computed tomography. The update group made recommendations that clinicians (1) should either offer watchful waiting (without antibiotics) or prescribe initial antibiotic therapy for adults with uncomplicated ABRS; (2) should prescribe amoxicillin with or without clavulanate as first-line therapy for 5 to 10 days (if a decision is made to treat ABRS with an antibiotic); (3) should reassess the patient to confirm ABRS, exclude other causes of illness, and detect complications if the patient worsens or fails to improve with the initial management option by 7 days after diagnosis or worsens during the initial management; (4) should distinguish CRS and recurrent ARS from isolated episodes of ABRS and other causes of sinonasal symptoms; (5) should assess the patient with CRS or recurrent ARS for multiple chronic conditions that would modify management, such as asthma, cystic fibrosis, immunocompromised state, and ciliary dyskinesia; (6) should confirm the presence or absence of nasal polyps in a patient with CRS; and (7) should recommend saline nasal irrigation, topical intranasal corticosteroids, or both for symptom relief of CRS. The update group stated as options that clinicians may (1) recommend analgesics, topical intranasal steroids, and/or nasal saline irrigation for symptomatic relief of viral rhinosinusitis; (2) recommend analgesics, topical intranasal steroids, and/or nasal saline irrigation) for symptomatic relief of ABRS; and (3) obtain testing for allergy and immune function in evaluating a patient with CRS or recurrent ARS. The update group made recommendations that clinicians (1) should not obtain radiographic imaging for patients who meet diagnostic criteria for ARS, unless a complication or alternative diagnosis is suspected, and (2) should not prescribe topical or systemic antifungal therapy for patients with CRS.
Topics: Academies and Institutes; Adult; Anti-Bacterial Agents; Humans; Otolaryngology; Rhinitis; Sinusitis; Societies, Medical; United States; Watchful Waiting
PubMed: 25832968
DOI: 10.1177/0194599815572097 -
European Journal of Obstetrics,... Sep 2023A Cesarean Scar Pregnancy (CSP) is a variant of uterine ectopic pregnancy defined by full or partial implantation of the gestational sac in the scar of a previous... (Review)
Review
A Cesarean Scar Pregnancy (CSP) is a variant of uterine ectopic pregnancy defined by full or partial implantation of the gestational sac in the scar of a previous cesarean section. The continuous increase of Cesarean Deliveries is causing a parallel increase in CSP and its complications. Considering its high morbidity, the most usual recommendation has been termination of pregnancy in the first trimester; however, several cases progress to viable births. The aim of this systematic review is to evaluate the outcome of CSP managed expectantly and understand whether sonographic signs could correlate to the outcomes. An online-based search of PubMed and Cochrane Library Databases was used to gather studies including women diagnosed with a CSP who were managed expectantly. The description of all cases was analysed by the authors in order to obtain information for each outcome. 47 studies of different types were retrieved, and the gestational outcome was available in 194 patients. Out of these, 39 patients (20,1%) had a miscarriage and 16 (8,3%) suffered foetal death. 50 patients (25,8%) had a term delivery and 81 (41,8%) patients had a preterm birth, out of which 27 (13,9%) delivered before 34 weeks of gestation. In 102 (52,6%) patients, a hysterectomy was performed. Placenta Accreta Spectrum (PAS) was a common disorder among CSP and was linked to a higher rate of complications such as foetal death, preterm birth, hysterectomy, haemorrhagic morbidity and surgical complications. Some of the analysed articles showed that sonographic signs with specific characteristics, such as type II and III CSP classification, Crossover Sign - 1, "In the niche" implantation and lower myometrial thickness could be related to worse outcomes of CSP. This article provides a good understanding of CSP as an entity that, although rare, presents with a high rate of relevant morbidity. It is also understood that pregnancies with confirmed PAS had an even higher rate of morbidity. Some sonographic signs were shown to predict the prognosis of these pregnancies and further investigation is necessary to validate one or more signs so they can be used for a more reliable counselling of women with CSP.
Topics: Pregnancy; Infant, Newborn; Humans; Female; Cesarean Section; Premature Birth; Cicatrix; Watchful Waiting; Pregnancy, Ectopic; Pregnancy Outcome; Placenta Accreta; Fetal Death; Retrospective Studies
PubMed: 37421745
DOI: 10.1016/j.ejogrb.2023.06.030 -
JAMA Jan 2024Adverse outcomes associated with treatments for localized prostate cancer remain unclear. (Comparative Study)
Comparative Study Observational Study
IMPORTANCE
Adverse outcomes associated with treatments for localized prostate cancer remain unclear.
OBJECTIVE
To compare rates of adverse functional outcomes between specific treatments for localized prostate cancer.
DESIGN, SETTING, AND PARTICIPANTS
An observational cohort study using data from 5 US Surveillance, Epidemiology, and End Results Program registries. Participants were treated for localized prostate cancer between 2011 and 2012. At baseline, 1877 had favorable-prognosis prostate cancer (defined as cT1-cT2bN0M0, prostate-specific antigen level <20 ng/mL, and grade group 1-2) and 568 had unfavorable-prognosis prostate cancer (defined as cT2cN0M0, prostate-specific antigen level of 20-50 ng/mL, or grade group 3-5). Follow-up data were collected by questionnaire through February 1, 2022.
EXPOSURES
Radical prostatectomy (n = 1043), external beam radiotherapy (n = 359), brachytherapy (n = 96), or active surveillance (n = 379) for favorable-prognosis disease and radical prostatectomy (n = 362) or external beam radiotherapy with androgen deprivation therapy (n = 206) for unfavorable-prognosis disease.
MAIN OUTCOMES AND MEASURES
Outcomes were patient-reported sexual, urinary, bowel, and hormone function measured using the 26-item Expanded Prostate Cancer Index Composite (range, 0-100; 100 = best). Associations of specific therapies with each outcome were estimated and compared at 10 years after treatment, adjusting for corresponding baseline scores, and patient and tumor characteristics. Minimum clinically important differences were 10 to 12 for sexual function, 6 to 9 for urinary incontinence, 5 to 7 for urinary irritation, and 4 to 6 for bowel and hormone function.
RESULTS
A total of 2445 patients with localized prostate cancer (median age, 64 years; 14% Black, 8% Hispanic) were included and followed up for a median of 9.5 years. Among 1877 patients with favorable prognosis, radical prostatectomy was associated with worse urinary incontinence (adjusted mean difference, -12.1 [95% CI, -16.2 to -8.0]), but not worse sexual function (adjusted mean difference, -7.2 [95% CI, -12.3 to -2.0]), compared with active surveillance. Among 568 patients with unfavorable prognosis, radical prostatectomy was associated with worse urinary incontinence (adjusted mean difference, -26.6 [95% CI, -35.0 to -18.2]), but not worse sexual function (adjusted mean difference, -1.4 [95% CI, -11.1 to 8.3), compared with external beam radiotherapy with androgen deprivation therapy. Among patients with unfavorable prognosis, external beam radiotherapy with androgen deprivation therapy was associated with worse bowel (adjusted mean difference, -4.9 [95% CI, -9.2 to -0.7]) and hormone (adjusted mean difference, -4.9 [95% CI, -9.5 to -0.3]) function compared with radical prostatectomy.
CONCLUSIONS AND RELEVANCE
Among patients treated for localized prostate cancer, radical prostatectomy was associated with worse urinary incontinence but not worse sexual function at 10-year follow-up compared with radiotherapy or surveillance among people with more favorable prognosis and compared with radiotherapy for those with unfavorable prognosis. Among men with unfavorable-prognosis disease, external beam radiotherapy with androgen deprivation therapy was associated with worse bowel and hormone function at 10-year follow-up compared with radical prostatectomy.
Topics: Humans; Male; Middle Aged; Androgen Antagonists; Prostate-Specific Antigen; Prostatic Neoplasms; Urinary Incontinence; United States; SEER Program; Aged; Prostatectomy; Patient Reported Outcome Measures; Prognosis; Watchful Waiting; Radiotherapy
PubMed: 38261043
DOI: 10.1001/jama.2023.26491 -
The Cochrane Database of Systematic... Jun 2021Miscarriage, defined as the spontaneous loss of a pregnancy before 24 weeks' gestation, is common with approximately 25% of women experiencing a miscarriage in their... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Miscarriage, defined as the spontaneous loss of a pregnancy before 24 weeks' gestation, is common with approximately 25% of women experiencing a miscarriage in their lifetime. An estimated 15% of pregnancies end in miscarriage. Miscarriage can lead to serious morbidity, including haemorrhage, infection, and even death, particularly in settings without adequate healthcare provision. Early miscarriages occur during the first 14 weeks of pregnancy, and can be managed expectantly, medically or surgically. However, there is uncertainty about the relative effectiveness and risks of each option.
OBJECTIVES
To estimate the relative effectiveness and safety profiles for the different management methods for early miscarriage, and to provide rankings of the available methods according to their effectiveness, safety, and side-effect profile using a network meta-analysis.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth's Trials Register (9 February 2021), ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) (12 February 2021), and reference lists of retrieved studies.
SELECTION CRITERIA
We included all randomised controlled trials assessing the effectiveness or safety of methods for miscarriage management. Early miscarriage was defined as less than or equal to 14 weeks of gestation, and included missed and incomplete miscarriage. Management of late miscarriages after 14 weeks of gestation (often referred to as intrauterine fetal deaths) was not eligible for inclusion in the review. Cluster- and quasi-randomised trials were eligible for inclusion. Randomised trials published only as abstracts were eligible if sufficient information could be retrieved. We excluded non-randomised trials.
DATA COLLECTION AND ANALYSIS
At least three review authors independently assessed the trials for inclusion and risk of bias, extracted data and checked them for accuracy. We estimated the relative effects and rankings for the primary outcomes of complete miscarriage and composite outcome of death or serious complications. The certainty of evidence was assessed using GRADE. Relative effects for the primary outcomes are reported subgrouped by the type of miscarriage (incomplete and missed miscarriage). We also performed pairwise meta-analyses and network meta-analysis to determine the relative effects and rankings of all available methods.
MAIN RESULTS
Our network meta-analysis included 78 randomised trials involving 17,795 women from 37 countries. Most trials (71/78) were conducted in hospital settings and included women with missed or incomplete miscarriage. Across 158 trial arms, the following methods were used: 51 trial arms (33%) used misoprostol; 50 (32%) used suction aspiration; 26 (16%) used expectant management or placebo; 17 (11%) used dilatation and curettage; 11 (6%) used mifepristone plus misoprostol; and three (2%) used suction aspiration plus cervical preparation. Of these 78 studies, 71 (90%) contributed data in a usable form for meta-analysis. Complete miscarriage Based on the relative effects from the network meta-analysis of 59 trials (12,591 women), we found that five methods may be more effective than expectant management or placebo for achieving a complete miscarriage: · suction aspiration after cervical preparation (risk ratio (RR) 2.12, 95% confidence interval (CI) 1.41 to 3.20, low-certainty evidence), · dilatation and curettage (RR 1.49, 95% CI 1.26 to 1.75, low-certainty evidence), · suction aspiration (RR 1.44, 95% CI 1.29 to 1.62, low-certainty evidence), · mifepristone plus misoprostol (RR 1.42, 95% CI 1.22 to 1.66, moderate-certainty evidence), · misoprostol (RR 1.30, 95% CI 1.16 to 1.46, low-certainty evidence). The highest ranked surgical method was suction aspiration after cervical preparation. The highest ranked non-surgical treatment was mifepristone plus misoprostol. All surgical methods were ranked higher than medical methods, which in turn ranked above expectant management or placebo. Composite outcome of death and serious complications Based on the relative effects from the network meta-analysis of 35 trials (8161 women), we found that four methods with available data were compatible with a wide range of treatment effects compared with expectant management or placebo: · dilatation and curettage (RR 0.43, 95% CI 0.17 to 1.06, low-certainty evidence), · suction aspiration (RR 0.55, 95% CI 0.23 to 1.32, low-certainty evidence), · misoprostol (RR 0.50, 95% CI 0.22 to 1.15, low-certainty evidence), · mifepristone plus misoprostol (RR 0.76, 95% CI 0.31 to 1.84, low-certainty evidence). Importantly, no deaths were reported in these studies, thus this composite outcome was entirely composed of serious complications, including blood transfusions, uterine perforations, hysterectomies, and intensive care unit admissions. Expectant management and placebo ranked the lowest when compared with alternative treatment interventions. Subgroup analyses by type of miscarriage (missed or incomplete) agreed with the overall analysis in that surgical methods were the most effective treatment, followed by medical methods and then expectant management or placebo, but there are possible subgroup differences in the effectiveness of the available methods. AUTHORS' CONCLUSIONS: Based on relative effects from the network meta-analysis, all surgical and medical methods for managing a miscarriage may be more effective than expectant management or placebo. Surgical methods were ranked highest for managing a miscarriage, followed by medical methods, which in turn ranked above expectant management or placebo. Expectant management or placebo had the highest chance of serious complications, including the need for unplanned or emergency surgery. A subgroup analysis showed that surgical and medical methods may be more beneficial in women with missed miscarriage compared to women with incomplete miscarriage. Since type of miscarriage (missed and incomplete) appears to be a source of inconsistency and heterogeneity within these data, we acknowledge that the main network meta-analysis may be unreliable. However, we plan to explore this further in future updates and consider the primary analysis as separate networks for missed and incomplete miscarriage.
Topics: Abortion, Incomplete; Abortion, Missed; Abortion, Spontaneous; Drug Therapy, Combination; Female; Humans; Mifepristone; Misoprostol; Network Meta-Analysis; Oxytocics; Placebos; Pregnancy; Pregnancy Trimester, First; Randomized Controlled Trials as Topic; Suction; Vacuum Curettage; Watchful Waiting
PubMed: 34061352
DOI: 10.1002/14651858.CD012602.pub2 -
JAMA May 2019Intravitreous injections of antivascular endothelial growth factor agents are effective for treating diabetic macular edema (DME) involving the center of the macula... (Comparative Study)
Comparative Study Randomized Controlled Trial
Effect of Initial Management With Aflibercept vs Laser Photocoagulation vs Observation on Vision Loss Among Patients With Diabetic Macular Edema Involving the Center of the Macula and Good Visual Acuity: A Randomized Clinical Trial.
IMPORTANCE
Intravitreous injections of antivascular endothelial growth factor agents are effective for treating diabetic macular edema (DME) involving the center of the macula (center-involved DME [CI-DME]) with visual acuity impairment (20/32 or worse). The best approach to treating patients with CI-DME and good visual acuity (20/25 or better) is unknown.
OBJECTIVE
To compare vision loss at 2 years among eyes initially managed with aflibercept, laser photocoagulation, or observation.
DESIGN, SETTING, AND PARTICIPANTS
Randomized clinical trial conducted at 91 US and Canadian sites among 702 adults with type 1 or type 2 diabetes. Participants had 1 study eye with CI-DME and visual acuity of 20/25 or better. The first participant was randomized on November 8, 2013, and the final date of follow-up was September 11, 2018.
INTERVENTIONS
Eyes were randomly assigned to 2.0 mg of intravitreous aflibercept (n = 226) as frequently as every 4 weeks, focal/grid laser photocoagulation (n = 240), or observation (n = 236). Aflibercept was required for eyes in the laser photocoagulation or observation groups that had decreased visual acuity from baseline by at least 10 letters (≥ 2 lines on an eye chart) at any visit or by 5 to 9 letters (1-2 lines) at 2 consecutive visits.
MAIN OUTCOMES AND MEASURES
The primary outcome was at least a 5-letter visual acuity decrease from baseline at 2 years. Antiplatelet Trialists' Collaboration adverse events (defined as myocardial infarction, stroke, or vascular or unknown death) were reported.
RESULTS
Among 702 randomized participants (mean age, 59 years; 38% female [n=264]), 625 of 681 (92% excluding deaths) completed the 2-year visit. For eyes with visual acuity that decreased from baseline, aflibercept was initiated in 25% (60/240) and 34% (80/236) in the laser photocoagulation and observation groups, respectively. At 2 years, the percentage of eyes with at least a 5-letter visual acuity decrease was 16% (33/205), 17% (36/212), and 19% (39/208) in the aflibercept, laser photocoagulation, and observation groups, respectively (aflibercept vs laser photocoagulation risk difference, -2% [95% CI, -9% to 5%]; relative risk, 0.88 [95% CI, 0.57-1.35; P = .79]; aflibercept vs observation risk difference, -3% [95% CI, -11% to 4%]; relative risk, 0.83 [95% CI, 0.55-1.27; P = .79]; laser photocoagulation vs observation risk difference, -1% [95% CI, -9% to 6%]; relative risk, 0.95 [95% CI, 0.64-1.41; P = .79]). Antiplatelet Trialists' Collaboration vascular events occurred in 15 (7%), 13 (5%), and 8 (3%) participants in the aflibercept, laser photocoagulation, and observation groups.
CONCLUSIONS AND RELEVANCE
Among eyes with CI-DME and good visual acuity, there was no significant difference in vision loss at 2 years whether eyes were initially managed with aflibercept or with laser photocoagulation or observation and given aflibercept only if visual acuity worsened. Observation without treatment unless visual acuity worsens may be a reasonable strategy for CI-DME.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT01909791.
Topics: Aged; Angiogenesis Inhibitors; Diabetic Retinopathy; Disease Progression; Female; Humans; Laser Coagulation; Macular Edema; Male; Middle Aged; Receptors, Vascular Endothelial Growth Factor; Recombinant Fusion Proteins; Vision Disorders; Visual Acuity; Watchful Waiting
PubMed: 31037289
DOI: 10.1001/jama.2019.5790 -
The Cochrane Database of Systematic... Jul 2020Risks of stillbirth or neonatal death increase as gestation continues beyond term (around 40 weeks' gestation). It is unclear whether a policy of labour induction can... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Risks of stillbirth or neonatal death increase as gestation continues beyond term (around 40 weeks' gestation). It is unclear whether a policy of labour induction can reduce these risks. This Cochrane Review is an update of a review that was originally published in 2006 and subsequently updated in 2012 and 2018.
OBJECTIVES
To assess the effects of a policy of labour induction at or beyond 37 weeks' gestation compared with a policy of awaiting spontaneous labour indefinitely (or until a later gestational age, or until a maternal or fetal indication for induction of labour arises) on pregnancy outcomes for the infant and the mother.
SEARCH METHODS
For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) (17 July 2019), and reference lists of retrieved studies.
SELECTION CRITERIA
Randomised controlled trials (RCTs) conducted in pregnant women at or beyond 37 weeks, comparing a policy of labour induction with a policy of awaiting spontaneous onset of labour (expectant management). We also included trials published in abstract form only. Cluster-RCTs, quasi-RCTs and trials using a cross-over design were not eligible for inclusion in this review. We included pregnant women at or beyond 37 weeks' gestation. Since risk factors at this stage of pregnancy would normally require intervention, only trials including women at low risk for complications, as defined by trialists, were eligible. The trials of induction of labour in women with prelabour rupture of membranes at or beyond term were not considered in this review but are considered in a separate Cochrane Review.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for inclusion, assessed risk of bias and extracted data. Data were checked for accuracy. We assessed the certainty of evidence using the GRADE approach.
MAIN RESULTS
In this updated review, we included 34 RCTs (reporting on over 21,000 women and infants) mostly conducted in high-income settings. The trials compared a policy to induce labour usually after 41 completed weeks of gestation (> 287 days) with waiting for labour to start and/or waiting for a period before inducing labour. The trials were generally at low to moderate risk of bias. Compared with a policy of expectant management, a policy of labour induction was associated with fewer (all-cause) perinatal deaths (risk ratio (RR) 0.31, 95% confidence interval (CI) 0.15 to 0.64; 22 trials, 18,795 infants; high-certainty evidence). There were four perinatal deaths in the labour induction policy group compared with 25 perinatal deaths in the expectant management group. The number needed to treat for an additional beneficial outcome (NNTB) with induction of labour, in order to prevent one perinatal death, was 544 (95% CI 441 to 1042). There were also fewer stillbirths in the induction group (RR 0.30, 95% CI 0.12 to 0.75; 22 trials, 18,795 infants; high-certainty evidence); two in the induction policy group and 16 in the expectant management group. For women in the policy of induction arms of trials, there were probably fewer caesarean sections compared with expectant management (RR 0.90, 95% CI 0.85 to 0.95; 31 trials, 21,030 women; moderate-certainty evidence); and probably little or no difference in operative vaginal births with induction (RR 1.03, 95% CI 0.96 to 1.10; 22 trials, 18,584 women; moderate-certainty evidence). Induction may make little or difference to perineal trauma (severe perineal tear: RR 1.04, 95% CI 0.85 to 1.26; 5 trials; 11,589 women; low-certainty evidence). Induction probably makes little or no difference to postpartum haemorrhage (RR 1.02, 95% CI 0.91 to 1.15, 9 trials; 12,609 women; moderate-certainty evidence), or breastfeeding at discharge (RR 1.00, 95% CI 0.96 to 1.04; 2 trials, 7487 women; moderate-certainty evidence). Very low certainty evidence means that we are uncertain about the effect of induction or expectant management on the length of maternal hospital stay (average mean difference (MD) -0.19 days, 95% CI -0.56 to 0.18; 7 trials; 4120 women; Tau² = 0.20; I² = 94%). Rates of neonatal intensive care unit (NICU) admission were lower (RR 0.88, 95% CI 0.80 to 0.96; 17 trials, 17,826 infants; high-certainty evidence), and probably fewer babies had Apgar scores less than seven at five minutes in the induction groups compared with expectant management (RR 0.73, 95% CI 0.56 to 0.96; 20 trials, 18,345 infants; moderate-certainty evidence). Induction or expectant management may make little or no difference for neonatal encephalopathy (RR 0.69, 95% CI 0.37 to 1.31; 2 trials, 8851 infants; low-certainty evidence, and probably makes little or no difference for neonatal trauma (RR 0.97, 95% CI 0.63 to 1.49; 5 trials, 13,106 infants; moderate-certainty evidence) for induction compared with expectant management. Neurodevelopment at childhood follow-up and postnatal depression were not reported by any trials. In subgroup analyses, no differences were seen for timing of induction (< 40 versus 40-41 versus > 41 weeks' gestation), by parity (primiparous versus multiparous) or state of cervix for any of the main outcomes (perinatal death, stillbirth, NICU admission, caesarean section, operative vaginal birth, or perineal trauma).
AUTHORS' CONCLUSIONS
There is a clear reduction in perinatal death with a policy of labour induction at or beyond 37 weeks compared with expectant management, though absolute rates are small (0.4 versus 3 deaths per 1000). There were also lower caesarean rates without increasing rates of operative vaginal births and there were fewer NICU admissions with a policy of induction. Most of the important outcomes assessed using GRADE had high- or moderate-certainty ratings. While existing trials have not yet reported on childhood neurodevelopment, this is an important area for future research. The optimal timing of offering induction of labour to women at or beyond 37 weeks' gestation needs further investigation, as does further exploration of risk profiles of women and their values and preferences. Offering women tailored counselling may help them make an informed choice between induction of labour for pregnancies, particularly those continuing beyond 41 weeks - or waiting for labour to start and/or waiting before inducing labour.
Topics: Cesarean Section; Female; Gestational Age; Humans; Infant; Infant Mortality; Infant, Newborn; Intensive Care Units, Neonatal; Labor, Induced; Perinatal Death; Pregnancy; Pregnancy, Prolonged; Randomized Controlled Trials as Topic; Risk; Stillbirth; Watchful Waiting
PubMed: 32666584
DOI: 10.1002/14651858.CD004945.pub5 -
Human Reproduction (Oxford, England) Apr 2021Does septum resection improve reproductive outcomes in women with a septate uterus? (Randomized Controlled Trial)
Randomized Controlled Trial
STUDY QUESTION
Does septum resection improve reproductive outcomes in women with a septate uterus?
SUMMARY ANSWER
Hysteroscopic septum resection does not improve reproductive outcomes in women with a septate uterus.
WHAT IS KNOWN ALREADY
A septate uterus is a congenital uterine anomaly. Women with a septate uterus are at increased risk of subfertility, pregnancy loss and preterm birth. Hysteroscopic resection of a septum may improve the chance of a live birth in affected women, but this has never been evaluated in randomized clinical trials. We assessed whether septum resection improves reproductive outcomes in women with a septate uterus, wanting to become pregnant.
STUDY DESIGN, SIZE, DURATION
We performed an international, multicentre, open-label, randomized controlled trial in 10 centres in The Netherlands, UK, USA and Iran between October 2010 and September 2018.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Women with a septate uterus and a history of subfertility, pregnancy loss or preterm birth were randomly allocated to septum resection or expectant management. The primary outcome was conception leading to live birth within 12 months after randomization, defined as the birth of a living foetus beyond 24 weeks of gestational age. We analysed the data on an intention-to-treat basis and calculated relative risks with 95% CI.
MAIN RESULTS AND THE ROLE OF CHANCE
We randomly assigned 80 women with a septate uterus to septum resection (n = 40) or expectant management (n = 40). We excluded one woman who underwent septum resection from the intention-to-treat analysis, because she withdrew informed consent for the study shortly after randomization. Live birth occurred in 12 of 39 women allocated to septum resection (31%) and in 14 of 40 women allocated to expectant management (35%) (relative risk (RR) 0.88 (95% CI 0.47 to 1.65)). There was one uterine perforation which occurred during surgery (1/39 = 2.6%).
LIMITATIONS, REASONS FOR CAUTION
Although this was a major international trial, the sample size was still limited and recruitment took a long period. Since surgical techniques did not fundamentally change over time, we consider the latter of limited clinical significance.
WIDER IMPLICATIONS OF THE FINDINGS
The trial generated high-level evidence in addition to evidence from a recently published large cohort study. Both studies unequivocally do not reveal any improvements in reproductive outcomes, thereby questioning any rationale behind surgery.
STUDY FUNDING/COMPETING INTEREST(S)
There was no study funding. M.H.E. reports a patent on a surgical endoscopic cutting device and process for the removal of tissue from a body cavity licensed to Medtronic, outside the scope of the submitted work. H.A.v.V. reports personal fees from Medtronic, outside the submitted work. B.W.J.M. reports grants from NHMRC, personal fees from ObsEva, personal fees from Merck Merck KGaA, personal fees from Guerbet, personal fees from iGenomix, outside the submitted work. M.G. reports several research and educational grants from Guerbet, Merck and Ferring (location VUMC) outside the scope of the submitted work. The remaining authors have nothing to declare.
TRIAL REGISTRATION NUMBER
Dutch trial registry: NTR 1676.
TRIAL REGISTRATION DATE
18 February 2009.
DATE OF FIRST PATIENT’S ENROLMENT
20 October 2010.
Topics: Cohort Studies; Female; Humans; Infant, Newborn; Iran; Netherlands; Pregnancy; Premature Birth; Uterus; Watchful Waiting
PubMed: 33793794
DOI: 10.1093/humrep/deab037 -
World Journal of Urology Jan 2022In the past two decades, new biomarkers for prostate cancer detection and risk prediction have become available for clinical use. While tissue-based gene expression... (Review)
Review
PURPOSE
In the past two decades, new biomarkers for prostate cancer detection and risk prediction have become available for clinical use. While tissue-based gene expression assays offer molecular risk assessment after diagnoses, several serum- and urine-based 'liquid' biomarkers are available for the pre-biopsy setting which may also play a role for active surveillance (AS).
METHODS
The medical literature was queried utilizing PubMed (pubmed.ncbi.nlm.nih.gov) for all relevant original publications describing prostate cancer biomarkers that can be identified in the blood, urine, or semen. Referenced studies must have defined patient inclusion criteria and descriptions of the biomarkers. Included studies investigated the utility of liquid biomarkers for selection or monitoring of men with prostate cancer for active surveillance.
RESULTS
PSA is the most common and readily available biomarker for prostate cancer diagnosis and treatment. Contemporary AS guidelines consider diagnostic PSA level in addition to other clinical factors when selecting men for this approach, with most recommending that initial PSA should be under 10 ng/ml. Serum PSA changes are associated with outcomes on AS but are not adequately sensitive so drive men to secondary treatment in isolation. PSA derivates including the Prostate Health Index (phi) and the 4K Score can predict higher grade cancer and may help tailor repeat prostate biopsy strategies, but further data are needed prior to routine clinic use. Several urine-based biomarkers including PCA3 and TMPRSS2:ERG levels have also been studied in the AS setting.
CONCLUSIONS
Multiple serum- and urine-based liquid biomarkers are available for use in men with prostate cancer. For AS, serum PSA is utilized in part for patient selection as well as to monitor disease over time. Models that incorporate PSA kinetics with other clinical characteristics may help tailor surveillance strategies to reduce disease burden and health care costs over time. Several novel liquid biomarkers demonstrate promise and may eventually have applications for prostate cancer surveillance as well.
Topics: Biomarkers, Tumor; Humans; Male; Prostatic Neoplasms; Semen; Watchful Waiting
PubMed: 33590279
DOI: 10.1007/s00345-021-03609-5