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JAMA Oncology Mar 2022The Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019) provided systematic estimates of incidence, morbidity, and mortality to inform local and...
Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life Years for 29 Cancer Groups From 2010 to 2019: A Systematic Analysis for the Global Burden of Disease Study 2019.
IMPORTANCE
The Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019) provided systematic estimates of incidence, morbidity, and mortality to inform local and international efforts toward reducing cancer burden.
OBJECTIVE
To estimate cancer burden and trends globally for 204 countries and territories and by Sociodemographic Index (SDI) quintiles from 2010 to 2019.
EVIDENCE REVIEW
The GBD 2019 estimation methods were used to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life years (DALYs) in 2019 and over the past decade. Estimates are also provided by quintiles of the SDI, a composite measure of educational attainment, income per capita, and total fertility rate for those younger than 25 years. Estimates include 95% uncertainty intervals (UIs).
FINDINGS
In 2019, there were an estimated 23.6 million (95% UI, 22.2-24.9 million) new cancer cases (17.2 million when excluding nonmelanoma skin cancer) and 10.0 million (95% UI, 9.36-10.6 million) cancer deaths globally, with an estimated 250 million (235-264 million) DALYs due to cancer. Since 2010, these represented a 26.3% (95% UI, 20.3%-32.3%) increase in new cases, a 20.9% (95% UI, 14.2%-27.6%) increase in deaths, and a 16.0% (95% UI, 9.3%-22.8%) increase in DALYs. Among 22 groups of diseases and injuries in the GBD 2019 study, cancer was second only to cardiovascular diseases for the number of deaths, years of life lost, and DALYs globally in 2019. Cancer burden differed across SDI quintiles. The proportion of years lived with disability that contributed to DALYs increased with SDI, ranging from 1.4% (1.1%-1.8%) in the low SDI quintile to 5.7% (4.2%-7.1%) in the high SDI quintile. While the high SDI quintile had the highest number of new cases in 2019, the middle SDI quintile had the highest number of cancer deaths and DALYs. From 2010 to 2019, the largest percentage increase in the numbers of cases and deaths occurred in the low and low-middle SDI quintiles.
CONCLUSIONS AND RELEVANCE
The results of this systematic analysis suggest that the global burden of cancer is substantial and growing, with burden differing by SDI. These results provide comprehensive and comparable estimates that can potentially inform efforts toward equitable cancer control around the world.
Topics: Disability-Adjusted Life Years; Global Burden of Disease; Global Health; Humans; Incidence; Neoplasms; Prevalence; Quality-Adjusted Life Years; Risk Factors
PubMed: 34967848
DOI: 10.1001/jamaoncol.2021.6987 -
JAMA Pediatrics Dec 2019Reliable estimates of the prevalence of childhood hypertension serve as the basis for adequate prevention and treatment. However, the prevalence of childhood... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Reliable estimates of the prevalence of childhood hypertension serve as the basis for adequate prevention and treatment. However, the prevalence of childhood hypertension has rarely been synthesized at the global level.
OBJECTIVE
To conduct a systematic review and meta-analysis to assess the prevalence of hypertension in the general pediatric population.
DATA SOURCES
PubMed, MEDLINE, Embase, Global Health, and Global Health Library were searched from inception until June 2018, using search terms related to hypertension (hypertension OR high blood pressure OR elevated blood pressure), children (children OR adolescents), and prevalence (prevalence OR epidemiology).
STUDY SELECTION
Studies that were conducted in the general pediatric population and quantified the prevalence of childhood hypertension were eligible. Included studies had blood pressure measurements from at least 3 separate occasions.
DATA EXTRACTION AND SYNTHESIS
Two authors independently extracted data. Random-effects meta-analysis was used to derive the pooled prevalence. Variations in the prevalence estimates in different subgroups, including age group, sex, setting, device, investigation period, BMI group, World Health Organization region and World Bank region, were examined by subgroup meta-analysis. Meta-regression was used to establish the age-specific prevalence of childhood hypertension and to assess its secular trend.
MAIN OUTCOMES AND MEASURES
Prevalence of childhood hypertension overall and by subgroup.
RESULTS
A total of 47 articles were included in the meta-analysis. The pooled prevalence was 4.00% (95% CI, 3.29%-4.78%) for hypertension, 9.67% (95% CI, 7.26%-12.38%) for prehypertension, 4.00% (95% CI, 2.10%-6.48%) for stage 1 hypertension, and 0.95% (95% CI, 0.48%-1.57%) for stage 2 hypertension in children 19 years and younger. In subgroup meta-analyses, the prevalence of childhood hypertension was higher when measured by aneroid sphygmomanometer (7.23% vs 4.59% by mercury sphygmomanometer vs 2.94% by oscillometric sphygmomanometer) and among overweight and obese children (15.27% and 4.99% vs 1.90% among normal-weight children). A trend of increasing prevalence of childhood hypertension was observed during the past 2 decades, with a relative increasing rate of 75% to 79% from 2000 to 2015. In 2015, the prevalence of hypertension ranged from 4.32% (95% CI, 2.79%-6.63%) among children aged 6 years to 3.28% (95% CI, 2.25%-4.77%) among those aged 19 years and peaked at 7.89% (95% CI, 5.75%-10.75%) among those aged 14 years.
CONCLUSIONS AND RELEVANCE
This study provides a global estimation of childhood hypertension prevalence based on blood pressure measurements in at least 3 separate visits. More high-quality epidemiologic investigations on childhood hypertension are still needed.
Topics: Child; Global Health; Humans; Hypertension; Prevalence
PubMed: 31589252
DOI: 10.1001/jamapediatrics.2019.3310 -
American Journal of Hematology Jul 2020COVID-19 is a systemic infection with a significant impact on the hematopoietic system and hemostasis. Lymphopenia may be considered as a cardinal laboratory finding,...
COVID-19 is a systemic infection with a significant impact on the hematopoietic system and hemostasis. Lymphopenia may be considered as a cardinal laboratory finding, with prognostic potential. Neutrophil/lymphocyte ratio and peak platelet/lymphocyte ratio may also have prognostic value in determining severe cases. During the disease course, longitudinal evaluation of lymphocyte count dynamics and inflammatory indices, including LDH, CRP and IL-6 may help to identify cases with dismal prognosis and prompt intervention in order to improve outcomes. Biomarkers, such high serum procalcitonin and ferritin have also emerged as poor prognostic factors. Furthermore, blood hypercoagulability is common among hospitalized COVID-19 patients. Elevated D-Dimer levels are consistently reported, whereas their gradual increase during disease course is particularly associated with disease worsening. Other coagulation abnormalities such as PT and aPTT prolongation, fibrin degradation products increase, with severe thrombocytopenia lead to life-threatening disseminated intravascular coagulation (DIC), which necessitates continuous vigilance and prompt intervention. So, COVID-19 infected patients, whether hospitalized or ambulatory, are at high risk for venous thromboembolism, and an early and prolonged pharmacological thromboprophylaxis with low molecular weight heparin is highly recommended. Last but not least, the need for assuring blood donations during the pandemic is also highlighted.
Topics: Anticoagulants; Betacoronavirus; Biomarkers; Blood Coagulation Tests; Blood Donors; C-Reactive Protein; COVID-19; COVID-19 Testing; Clinical Laboratory Techniques; Coronavirus Infections; Cytokine Release Syndrome; Cytokines; Disseminated Intravascular Coagulation; Early Diagnosis; Ferritins; Fibrin Fibrinogen Degradation Products; Humans; Lymphopenia; Meta-Analysis as Topic; Pandemics; Pneumonia, Viral; Risk; SARS-CoV-2; Thrombophilia; Venous Thromboembolism
PubMed: 32282949
DOI: 10.1002/ajh.25829 -
The Cochrane Database of Systematic... May 2017For centuries, there has been controversy around whether being upright (sitting, birthing stools, chairs, squatting, kneeling) or lying down (lateral (Sim's) position,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
For centuries, there has been controversy around whether being upright (sitting, birthing stools, chairs, squatting, kneeling) or lying down (lateral (Sim's) position, semi-recumbent, lithotomy position, Trendelenburg's position) have advantages for women giving birth to their babies. This is an update of a review previously published in 2012, 2004 and 1999.
OBJECTIVES
To determine the possible benefits and risks of the use of different birth positions during the second stage of labour without epidural anaesthesia, on maternal, fetal, neonatal and caregiver outcomes.
SEARCH METHODS
We searched Cochrane Pregnancy and Childbirth's Trials Register (30 November 2016) and reference lists of retrieved studies.
SELECTION CRITERIA
Randomised, quasi-randomised or cluster-randomised controlled trials of any upright position assumed by pregnant women during the second stage of labour compared with supine or lithotomy positions. Secondary comparisons include comparison of different upright positions and the supine position. Trials in abstract form were included.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for inclusion and assessed trial quality. At least two review authors extracted the data. Data were checked for accuracy. The quality of the evidence was assessed using the GRADE approach.
MAIN RESULTS
Results should be interpreted with caution because risk of bias of the included trials was variable. We included eleven new trials for this update; there are now 32 included studies, and one trial is ongoing. Thirty trials involving 9015 women contributed to the analysis. Comparisons include any upright position, birth or squat stool, birth cushion, and birth chair versus supine positions.In all women studied (primigravid and multigravid), when compared with supine positions, the upright position was associated with a reduction in duration of second stage in the upright group (MD -6.16 minutes, 95% CI -9.74 to -2.59 minutes; 19 trials; 5811 women; P = 0.0007; random-effects; I² = 91%; very low-quality evidence); however, this result should be interpreted with caution due to large differences in size and direction of effect in individual studies. Upright positions were also associated with no clear difference in the rates of caesarean section (RR 1.22, 95% CI 0.81 to 1.81; 16 trials; 5439 women; low-quality evidence), a reduction in assisted deliveries (RR 0.75, 95% CI 0.66 to 0.86; 21 trials; 6481 women; moderate-quality evidence), a reduction in episiotomies (average RR 0.75, 95% CI 0.61 to 0.92; 17 trials; 6148 women; random-effects; I² = 88%), a possible increase in second degree perineal tears (RR 1.20, 95% CI 1.00 to 1.44; 18 trials; 6715 women; I² = 43%; low-quality evidence), no clear difference in the number of third or fourth degree perineal tears (RR 0.72, 95% CI 0.32 to 1.65; 6 trials; 1840 women; very low-quality evidence), increased estimated blood loss greater than 500 mL (RR 1.48, 95% CI 1.10 to 1.98; 15 trials; 5615 women; I² = 33%; moderate-quality evidence), fewer abnormal fetal heart rate patterns (RR 0.46, 95% CI 0.22 to 0.93; 2 trials; 617 women), no clear difference in the number of babies admitted to neonatal intensive care (RR 0.79, 95% CI 0.51 to 1.21; 4 trials; 2565 infants; low-quality evidence). On sensitivity analysis excluding trials with high risk of bias, these findings were unchanged except that there was no longer a clear difference in duration of second stage of labour (MD -4.34, 95% CI -9.00 to 0.32; 21 trials; 2499 women; I² = 85%).The main reasons for downgrading of GRADE assessment was that several studies had design limitations (inadequate randomisation and allocation concealment) with high heterogeneity and wide CIs.
AUTHORS' CONCLUSIONS
The findings of this review suggest several possible benefits for upright posture in women without epidural anaesthesia, such as a very small reduction in the duration of second stage of labour (mainly from the primigravid group), reduction in episiotomy rates and assisted deliveries. However, there is an increased risk blood loss greater than 500 mL and there may be an increased risk of second degree tears, though we cannot be certain of this. In view of the variable risk of bias of the trials reviewed, further trials using well-designed protocols are needed to ascertain the true benefits and risks of various birth positions.
Topics: Anesthesia, Epidural; Cesarean Section; Delivery, Obstetric; Episiotomy; Female; Hemorrhage; Humans; Labor Stage, Second; Patient Positioning; Perineum; Pregnancy; Randomized Controlled Trials as Topic; Supine Position; Time Factors; Uterine Hemorrhage
PubMed: 28539008
DOI: 10.1002/14651858.CD002006.pub4 -
PLoS Medicine Oct 2021Suboptimal diets are a leading risk factor for death and disability. Nutrition labelling is a potential method to encourage consumers to improve dietary behaviour. This... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Suboptimal diets are a leading risk factor for death and disability. Nutrition labelling is a potential method to encourage consumers to improve dietary behaviour. This systematic review and network meta-analysis (NMA) summarises evidence on the impact of colour-coded interpretive labels and warning labels on changing consumers' purchasing behaviour.
METHODS AND FINDINGS
We conducted a literature review of peer-reviewed articles published between 1 January 1990 and 24 May 2021 in PubMed, Embase via Ovid, Cochrane Central Register of Controlled Trials, and SCOPUS. Randomised controlled trials (RCTs) and quasi-experimental studies were included for the primary outcomes (measures of changes in consumers' purchasing and consuming behaviour). A frequentist NMA method was applied to pool the results. A total of 156 studies (including 101 RCTs and 55 non-RCTs) nested in 138 articles were incorporated into the systematic review, of which 134 studies in 120 articles were eligible for meta-analysis. We found that the traffic light labelling system (TLS), nutrient warning (NW), and health warning (HW) were associated with an increased probability of selecting more healthful products (odds ratios [ORs] and 95% confidence intervals [CIs]: TLS, 1.5 [1.2, 1.87]; NW, 3.61 [2.82, 4.63]; HW, 1.65 [1.32, 2.06]). Nutri-Score (NS) and warning labels appeared effective in reducing consumers' probability of selecting less healthful products (NS, 0.66 [0.53, 0.82]; NW,0.65 [0.54, 0.77]; HW,0.64 [0.53, 0.76]). NS and NW were associated with an increased overall healthfulness (healthfulness ratings of products purchased using models such as FSAm-NPS/HCSP) by 7.9% and 26%, respectively. TLS, NS, and NW were associated with a reduced energy (total energy: TLS, -6.5%; NS, -6%; NW, -12.9%; energy per 100 g/ml: TLS, -3%; NS, -3.5%; NW, -3.8%), sodium (total sodium/salt: TLS, -6.4%; sodium/salt per 100 g/ml: NS: -7.8%), fat (total fat: NS, -15.7%; fat per 100 g/ml: TLS: -2.6%; NS: -3.2%), and total saturated fat (TLS, -12.9%; NS: -17.1%; NW: -16.3%) content of purchases. The impact of TLS, NS, and NW on purchasing behaviour could be explained by improved understanding of the nutrition information, which further elicits negative perception towards unhealthful products or positive attitudes towards healthful foods. Comparisons across label types suggested that colour-coded labels performed better in nudging consumers towards the purchase of more healthful products (NS versus NW: 1.51 [1.08, 2.11]), while warning labels have the advantage in discouraging unhealthful purchasing behaviour (NW versus TLS: 0.81 [0.67, 0.98]; HW versus TLS: 0.8 [0.63, 1]). Study limitations included high heterogeneity and inconsistency in the comparisons across different label types, limited number of real-world studies (95% were laboratory studies), and lack of long-term impact assessments.
CONCLUSIONS
Our systematic review provided comprehensive evidence for the impact of colour-coded labels and warnings in nudging consumers' purchasing behaviour towards more healthful products and the underlying psychological mechanism of behavioural change. Each type of label had different attributes, which should be taken into consideration when making front-of-package nutrition labelling (FOPL) policies according to local contexts. Our study supported mandatory front-of-pack labelling policies in directing consumers' choice and encouraging the food industry to reformulate their products.
PROTOCOL REGISTRY
PROSPERO (CRD42020161877).
Topics: Adolescent; Adult; Attention; Child; Color; Consumer Behavior; Female; Food Labeling; Health Communication; Humans; Logic; Male; Nutritive Value; Perception; Risk Factors; Self Report
PubMed: 34610024
DOI: 10.1371/journal.pmed.1003765 -
Nutrients Jan 2021Calcium supplementation and fortification are strategies widely used to prevent adverse outcome in population with low-calcium intake which is highly frequent in... (Meta-Analysis)
Meta-Analysis Review
Calcium supplementation and fortification are strategies widely used to prevent adverse outcome in population with low-calcium intake which is highly frequent in low-income settings. We aimed to determine the effectiveness and cost-effectiveness of calcium fortified foods on calcium intake and related health, or economic outcomes. We performed a systematic review and meta-analysis involving participants of any age or gender, drawn from the general population. We searched PubMed, Agricola, EMBASE, CINAHL, Global Health, EconLit, the FAO website and Google until June 2019, without language restrictions. Pair of reviewers independently selected, extracted data and assessed the risk of bias of included studies using Covidence software. Disagreements were resolved by consensus. We performed meta-analyses using RevMan 5.4 and subgroup analyses by study design, age group, and fortification levels. We included 20 studies of which 15 were randomized controlled trials (RCTs), three were non-randomised studies and two were economic evaluations. Most RCTs had high risk of bias on randomization or blinding. Most represented groups were women and children from 1 to 72 months, most common intervention vehicles were milk and bakery products with a fortification levels between 96 and 1200 mg per 100 g of food. Calcium intake increased in the intervention groups between 460 mg (children) and 1200 mg (postmenopausal women). Most marked effects were seen in children. Compared to controls, height increased 0.83 cm (95% CI 0.00; 1.65), plasma parathyroid hormone decreased -1.51 pmol/L, (-2.37; -0.65), urine:calcium creatinine ratio decreased -0.05, (-0.07; -0.03), femoral neck and hip bone mineral density increased 0.02 g/cm (0.01; 0.04) and 0.03 g/cm (0.00; 0.06), respectively. The largest cost savings (43%) reported from calcium fortification programs came from prevented hip fractures in older women from Germany. Our study highlights that calcium fortification leads to a higher calcium intake, small benefits in children's height and bone health and also important evidence gaps for other outcomes and populations that could be solved with high quality experimental or quasi-experimental studies in relevant groups, especially as some evidence of calcium supplementation show controversial results on the bone health benefit on older adults.
Topics: Aged; Bone Density; Calcium; Calcium, Dietary; Child; Child, Preschool; Female; Food, Fortified; Hip Fractures; Humans; Infant; Male
PubMed: 33499250
DOI: 10.3390/nu13020316 -
Annals of Internal Medicine Jul 2012Although approximately 85 million units of red blood cells (RBCs) are transfused annually worldwide, transfusion practices vary widely. The AABB (formerly, the American... (Review)
Review
DESCRIPTION
Although approximately 85 million units of red blood cells (RBCs) are transfused annually worldwide, transfusion practices vary widely. The AABB (formerly, the American Association of Blood Banks) developed this guideline to provide clinical recommendations about hemoglobin concentration thresholds and other clinical variables that trigger RBC transfusions in hemodynamically stable adults and children.
METHODS
These guidelines are based on a systematic review of randomized clinical trials evaluating transfusion thresholds. We performed a literature search from 1950 to February 2011 with no language restrictions. We examined the proportion of patients who received any RBC transfusion and the number of RBC units transfused to describe the effect of restrictive transfusion strategies on RBC use. To determine the clinical consequences of restrictive transfusion strategies, we examined overall mortality, nonfatal myocardial infarction, cardiac events, pulmonary edema, stroke, thromboembolism, renal failure, infection, hemorrhage, mental confusion, functional recovery, and length of hospital stay. RECOMMENDATION 1: The AABB recommends adhering to a restrictive transfusion strategy (7 to 8 g/dL) in hospitalized, stable patients (Grade: strong recommendation; high-quality evidence). RECOMMENDATION 2: The AABB suggests adhering to a restrictive strategy in hospitalized patients with preexisting cardiovascular disease and considering transfusion for patients with symptoms or a hemoglobin level of 8 g/dL or less (Grade: weak recommendation; moderate-quality evidence). RECOMMENDATION 3: The AABB cannot recommend for or against a liberal or restrictive transfusion threshold for hospitalized, hemodynamically stable patients with the acute coronary syndrome (Grade: uncertain recommendation; very low-quality evidence). RECOMMENDATION 4: The AABB suggests that transfusion decisions be influenced by symptoms as well as hemoglobin concentration (Grade: weak recommendation; low-quality evidence).
Topics: Acute Coronary Syndrome; Adult; Blood Banks; Child; Decision Support Techniques; Erythrocyte Transfusion; Guideline Adherence; Hemoglobin A; Hospitalization; Humans; Randomized Controlled Trials as Topic; United States
PubMed: 22751760
DOI: 10.7326/0003-4819-157-1-201206190-00429 -
PloS One 2018School food environment policies may be a critical tool to promote healthy diets in children, yet their effectiveness remains unclear. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
School food environment policies may be a critical tool to promote healthy diets in children, yet their effectiveness remains unclear.
OBJECTIVE
To systematically review and quantify the impact of school food environment policies on dietary habits, adiposity, and metabolic risk in children.
METHODS
We systematically searched online databases for randomized or quasi-experimental interventions assessing effects of school food environment policies on children's dietary habits, adiposity, or metabolic risk factors. Data were extracted independently and in duplicate, and pooled using inverse-variance random-effects meta-analysis. Habitual (within+outside school) dietary intakes were the primary outcome. Heterogeneity was explored using meta-regression and subgroup analysis. Funnel plots, Begg's and Egger's test evaluated potential publication bias.
RESULTS
From 6,636 abstracts, 91 interventions (55 in US/Canada, 36 in Europe/New Zealand) were included, on direct provision of healthful foods/beverages (N = 39 studies), competitive food/beverage standards (N = 29), and school meal standards (N = 39) (some interventions assessed multiple policies). Direct provision policies, which largely targeted fruits and vegetables, increased consumption of fruits by 0.27 servings/d (n = 15 estimates (95%CI: 0.17, 0.36)) and combined fruits and vegetables by 0.28 servings/d (n = 16 (0.17, 0.40)); with a slight impact on vegetables (n = 11; 0.04 (0.01, 0.08)), and no effects on total calories (n = 6; -56 kcal/d (-174, 62)). In interventions targeting water, habitual intake was unchanged (n = 3; 0.33 glasses/d (-0.27, 0.93)). Competitive food/beverage standards reduced sugar-sweetened beverage intake by 0.18 servings/d (n = 3 (-0.31, -0.05)); and unhealthy snacks by 0.17 servings/d (n = 2 (-0.22, -0.13)), without effects on total calories (n = 5; -79 kcal/d (-179, 21)). School meal standards (mainly lunch) increased fruit intake (n = 2; 0.76 servings/d (0.37, 1.16)) and reduced total fat (-1.49%energy; n = 6 (-2.42, -0.57)), saturated fat (n = 4; -0.93%energy (-1.15, -0.70)) and sodium (n = 4; -170 mg/d (-242, -98)); but not total calories (n = 8; -38 kcal/d (-137, 62)). In 17 studies evaluating adiposity, significant decreases were generally not identified; few studies assessed metabolic factors (blood lipids/glucose/pressure), with mixed findings. Significant sources of heterogeneity or publication bias were not identified.
CONCLUSIONS
Specific school food environment policies can improve targeted dietary behaviors; effects on adiposity and metabolic risk require further investigation. These findings inform ongoing policy discussions and debates on best practices to improve childhood dietary habits and health.
Topics: Adiposity; Child; Child Behavior; Child Nutritional Physiological Phenomena; Cost-Benefit Analysis; Feeding Behavior; Food Services; Guidelines as Topic; Humans; Nutrition Policy; Obesity; Program Evaluation; Schools
PubMed: 29596440
DOI: 10.1371/journal.pone.0194555 -
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 -
The Cochrane Database of Systematic... Nov 2020Postpartum haemorrhage (PPH), defined as a blood loss of 500 mL or more after birth, is the leading cause of maternal death worldwide. The World Health Organization... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Postpartum haemorrhage (PPH), defined as a blood loss of 500 mL or more after birth, is the leading cause of maternal death worldwide. The World Health Organization (WHO) recommends that all women giving birth should receive a prophylactic uterotonic agent. Despite the routine administration of a uterotonic agent for prevention, PPH remains a common complication causing one-quarter of all maternal deaths globally. When prevention fails and PPH occurs, further administration of uterotonic agents as 'first-line' treatment is recommended. However, there is uncertainty about which uterotonic agent is best for the 'first-line' treatment of PPH.
OBJECTIVES
To identify the most effective uterotonic agent(s) with the least side-effects for PPH treatment, and generate a meaningful ranking among all available agents according to their relative effectiveness and side-effect profile.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (5 May 2020), and the reference lists of all retrieved studies.
SELECTION CRITERIA
All randomised controlled trials or cluster-randomised trials comparing the effectiveness and safety of uterotonic agents with other uterotonic agents for the treatment of PPH were eligible for inclusion.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed all trials for inclusion, extracted data and assessed each trial for risk of bias. Our primary outcomes were additional blood loss of 500 mL or more after recruitment to the trial until cessation of active bleeding and the composite outcome of maternal death or severe morbidity. Secondary outcomes included blood loss-related outcomes, morbidity outcomes, and patient-reported outcomes. We performed pairwise meta-analyses and indirect comparisons, where possible, but due to the limited number of included studies, we were unable to conduct the planned network meta-analysis. We used the GRADE approach to assess the certainty of evidence.
MAIN RESULTS
Seven trials, involving 3738 women in 10 countries, were included in this review. All trials were conducted in hospital settings. Randomised women gave birth vaginally, except in one small trial, where women gave birth either vaginally or by caesarean section. Across the seven trials (14 trial arms) the following agents were used: six trial arms used oxytocin alone; four trial arms used misoprostol plus oxytocin; three trial arms used misoprostol; one trial arm used Syntometrine® (oxytocin and ergometrine fixed-dose combination) plus oxytocin infusion. Pairwise meta-analysis of two trials (1787 participants), suggests that misoprostol, as first-line treatment uterotonic agent, probably increases the risk of blood transfusion (risk ratio (RR) 1.47, 95% confidence interval (CI) 1.02 to 2.14, moderate-certainty) compared with oxytocin. Low-certainty evidence suggests that misoprostol administration may increase the incidence of additional blood loss of 1000 mL or more (RR 2.57, 95% CI 1.00 to 6.64). The data comparing misoprostol with oxytocin is imprecise, with a wide range of treatment effects for the additional blood loss of 500 mL or more (RR 1.66, 95% CI 0.69 to 4.02, low-certainty), maternal death or severe morbidity (RR 1.98, 95% CI 0.36 to 10.72, low-certainty, based on one study n = 809 participants, as the second study had zero events), and the use of additional uterotonics (RR 1.30, 95% CI 0.57 to 2.94, low-certainty). The risk of side-effects may be increased with the use of misoprostol compared with oxytocin: vomiting (2 trials, 1787 participants, RR 2.47, 95% CI 1.37 to 4.47, high-certainty) and fever (2 trials, 1787 participants, RR 3.43, 95% CI 0.65 to 18.18, low-certainty). According to pairwise meta-analysis of four trials (1881 participants) generating high-certainty evidence, misoprostol plus oxytocin makes little or no difference to the use of additional uterotonics (RR 0.99, 95% CI 0.94 to 1.05) and to blood transfusion (RR 0.95, 95% CI 0.77 to 1.17) compared with oxytocin. We cannot rule out an important benefit of using the misoprostol plus oxytocin combination over oxytocin alone, for additional blood loss of 500 mL or more (RR 0.84, 95% CI 0.66 to 1.06, moderate-certainty). We also cannot rule out important benefits or harms for additional blood loss of 1000 mL or more (RR 0.76, 95% CI 0.43 to 1.34, moderate-certainty, 3 trials, 1814 participants, one study reported zero events), and maternal mortality or severe morbidity (RR 1.09, 95% CI 0.35 to 3.39, moderate-certainty). Misoprostol plus oxytocin increases the incidence of fever (4 trials, 1866 participants, RR 3.07, 95% CI 2.62 to 3.61, high-certainty), and vomiting (2 trials, 1482 participants, RR 1.85, 95% CI 1.16 to 2.95, high-certainty) compared with oxytocin alone. For all outcomes of interest, the available evidence on the misoprostol versus Syntometrine® plus oxytocin combination was of very low-certainty and these effects remain unclear. Although network meta-analysis was not performed, we were able to compare the misoprostol plus oxytocin combination with misoprostol alone through the common comparator of oxytocin. This indirect comparison suggests that the misoprostol plus oxytocin combination probably reduces the risk of blood transfusion (RR 0.65, 95% CI 0.42 to 0.99, moderate-certainty) and may reduce the risk of additional blood loss of 1000 mL or more (RR 0.30, 95% CI 0.10 to 0.89, low-certainty) compared with misoprostol alone. The combination makes little or no difference to vomiting (RR 0.75, 95% CI 0.35 to 1.59, high-certainty) compared with misoprostol alone. Misoprostol plus oxytocin compared to misoprostol alone are compatible with a wide range of treatment effects for additional blood loss of 500 mL or more (RR 0.51, 95% CI 0.20 to 1.26, low-certainty), maternal mortality or severe morbidity (RR 0.55, 95% CI 0.07 to 4.24, low-certainty), use of additional uterotonics (RR 0.76, 95% CI 0.33 to 1.73, low-certainty), and fever (RR 0.90, 95% CI 0.17 to 4.77, low-certainty).
AUTHORS' CONCLUSIONS
The available evidence suggests that oxytocin used as first-line treatment of PPH probably is more effective than misoprostol with less side-effects. Adding misoprostol to the conventional treatment of oxytocin probably makes little or no difference to effectiveness outcomes, and is also associated with more side-effects. The evidence for most uterotonic agents used as first-line treatment of PPH is limited, with no evidence found for commonly used agents, such as injectable prostaglandins, ergometrine, and Syntometrine®.
Topics: Bias; Blood Transfusion; Confidence Intervals; Drug Therapy, Combination; Ergonovine; Female; Humans; Misoprostol; Network Meta-Analysis; Oxytocics; Oxytocin; Postpartum Hemorrhage; Pregnancy; Randomized Controlled Trials as Topic
PubMed: 33232518
DOI: 10.1002/14651858.CD012754.pub2