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Andrology Mar 2022Male hypogonadism is a clinical and biochemical androgen insufficiency syndrome, becoming more prevalent with age. Exogenous testosterone is first-choice therapy, with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Male hypogonadism is a clinical and biochemical androgen insufficiency syndrome, becoming more prevalent with age. Exogenous testosterone is first-choice therapy, with several side effects, including negative feedback of the hypothalamic-pituitary-gonadal axis, resulting in suppression of intratesticular testosterone production and spermatogenesis. To preserve these testicular functions while treating male hypogonadism, clomiphene citrate is used as off-label therapy. This systematic review and meta-analysis aimed to evaluate the effectiveness and safety of clomiphene citrate therapy for men with hypogonadism.
METHODS
The EMBASE, PubMed, Cochrane databases were searched in May 2021, for effectiveness studies of men with hypogonadism treated with clomiphene citrate. Both intervention and observational studies were included. The Effective Public Health Practice Project Quality Assessment Tool, a validated instrument, was used to assess methodological study quality. The primary outcome measure was the evaluation of serum hormone concentration. Secondary outcomes were symptoms of hypogonadism, metabolic and lipid profile, side effects, safety aspects.
RESULTS
We included 19 studies, comprising four randomized controlled trials and 15 observational studies, resulting in 1642 patients. Seventeen studies were included in the meta-analysis, with a total of 1279 patients. Therapy and follow-up duration varied between one and a half and 52 months. Total testosterone increased with 2.60 (95% CI 1.82-3.38) during clomiphene citrate treatment. An increase was also seen in free testosterone, luteinizing hormone, follicle stimulating hormone, sex hormone-binding globulin and estradiol. Different symptom scoring methods were used in the included studies. The most frequently used instrument was the Androgen Deficiency in Aging Males questionnaire, whose improved during treatment. Reported side effects were only prevalent in less than 10% of the study populations and no serious adverse events were reported.
CONCLUSION
Clomiphene citrate is an effective therapy for improving both biochemical as well as clinical symptoms of males suffering from hypogonadism. Clomiphene citrate has few reported side effects and good safety aspects.
Topics: Clomiphene; Follicle Stimulating Hormone; Humans; Hypogonadism; Luteinizing Hormone; Male; Testosterone
PubMed: 34933414
DOI: 10.1111/andr.13146 -
Psychoneuroendocrinology Oct 2020Postpartum depression (PPD) is a significant mental health concern, especially for women in vulnerable populations. Oxytocin (OT), a hormone essential for a variety of...
Postpartum depression (PPD) is a significant mental health concern, especially for women in vulnerable populations. Oxytocin (OT), a hormone essential for a variety of maternal tasks, including labor, lactation, and infant bonding, has also been hypothesized to have a role in postpartum depression. Women are routinely given synthetic oxytocin to induce or augment labor and to prevent postpartum hemorrhage. The aim of this study was to review the quality and reliability of literature that examines potential relationships between OT and PPD to determine if there is sufficient data to reliably assess the strength of these relationships. We conducted a literature search in December of 2018 using five databases (PubMed, Web of Science, Embase, PsycInfo, and CINAHL). Eligible studies were identified, selected, and appraised using the Newcastle-Ottawa quality assessment scale and Cochrane Collaboration's tool for assessing risk of bias, as appropriate. Sixteen studies were included in the analysis and broken into two categories: correlations of endogenous OT with PPD and administration of synthetic OT with PPD. Depressive symptoms were largely measured using the Edinburgh Postnatal Depression Scale. OT levels were predominately measured in plasma, though there were differences in laboratory methodology and control of confounders (primarily breast feeding). Of the twelve studies focused on endogenous oxytocin, eight studies suggested an inverse relationship between plasma OT levels and depressive symptoms. We are not able to draw any conclusions regarding the relationship between intravenous synthetic oxytocin and postpartum depression based on current evidence due to the heterogeneity and small number of studies (n = 4). Considering limitations of the current literature and the current clinical prevalence of synthetic OT administration, we strongly recommend that rigorous studies examining the effects of synthetic OT exposure on PPD should be performed as well as continued work in defining the relationship between endogenous OT and PPD.
Topics: Adult; Anxiety; Breast Feeding; Depression; Depression, Postpartum; Female; Humans; Infant; Lactation; Mothers; Oxytocin; Postpartum Period; Pregnancy; Reproducibility of Results
PubMed: 32683141
DOI: 10.1016/j.psyneuen.2020.104793 -
Molecular Autism Mar 2022There is still no approved medication for the core symptoms of autism spectrum disorder (ASD). This network meta-analysis investigated pharmacological and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
There is still no approved medication for the core symptoms of autism spectrum disorder (ASD). This network meta-analysis investigated pharmacological and dietary-supplement treatments for ASD.
METHODS
We searched for randomized-controlled-trials (RCTs) with a minimum duration of seven days in ClinicalTrials.gov, EMBASE, MEDLINE, PsycINFO, WHO-ICTRP (from inception up to July 8, 2018), CENTRAL and PubMed (up to November 3, 2021). The co-primary outcomes were core symptoms (social-communication difficulties-SCD, repetitive behaviors-RB, overall core symptoms-OCS) measured by validated scales and standardized-mean-differences (SMDs). Associated symptoms, e.g., irritability/aggression and attention-deficit/hyperactivity disorder (ADHD) symptoms, dropouts and important side-effects, were investigated as secondary outcomes. Studies in children/adolescents and adults were analyzed separately in random-effects pairwise and network meta-analyses.
RESULTS
We analyzed data for 41 drugs and 17 dietary-supplements, from 125 RCTs (n = 7450 participants) in children/adolescents and 18 RCTs (n = 1104) in adults. The following medications could improve at least one core symptom domain in comparison with placebo: aripiprazole (k = 6 studies in analysis, SCD: SMD = 0.27 95% CI [0.09, 0.44], RB: 0.48 [0.26, 0.70]), atomoxetine (k = 3, RB:0.49 [0.18, 0.80]), bumetanide (k = 4, RB: 0.35 [0.09, 0.62], OCS: 0.61 [0.31, 0.91]), and risperidone (k = 4, SCM: 0.31 [0.06, 0.55], RB: 0.60 [0.29, 0.90]; k = 3, OCS: 1.18 [0.75, 1.61]) in children/adolescents; fluoxetine (k = 1, RB: 1.20 [0.45, 1.96]), fluvoxamine (k = 1, RB: 1.04 [0.27, 1.81]), oxytocin (k = 6, RB:0.41 [0.16, 0.66]) and risperidone (k = 1, RB: 0.97 [0.21,1.74]) in adults. There were some indications of improvement by carnosine, haloperidol, folinic acid, guanfacine, omega-3-fatty-acids, probiotics, sulforaphane, tideglusib and valproate, yet imprecise and not robust. Confidence in these estimates was very low or low, except moderate for oxytocin. Medications differed substantially in improving associated symptoms, and in their side-effect profiles.
LIMITATIONS
Most of the studies were inadequately powered (sample sizes of 20-80 participants), with short duration (8-13 weeks), and about a third focused on associated symptoms. Networks were mainly star-shaped, and there were indications of reporting bias. There was no optimal rating scale measuring change in core symptoms.
CONCLUSIONS
Some medications could improve core symptoms, although this could be likely secondary to the improvement of associated symptoms. Evidence on their efficacy and safety is preliminary; therefore, routine prescription of medications for the core symptoms cannot be recommended. Trial registration PROSPERO-ID CRD42019125317.
Topics: Adolescent; Adult; Attention Deficit Disorder with Hyperactivity; Autism Spectrum Disorder; Child; Humans; Network Meta-Analysis; Oxytocin; Risperidone
PubMed: 35246237
DOI: 10.1186/s13229-022-00488-4 -
Pharmacological Research Jul 2023We evaluated the efficacy, safety, adherence, quality of life (QoL) and cost-effectiveness of long-acting growth hormone (LAGH) vs daily growth hormone (GH) preparations... (Meta-Analysis)
Meta-Analysis Review
Efficacy, safety, quality of life, adherence and cost-effectiveness of long-acting growth hormone replacement therapy compared to daily growth hormone in children with growth hormone deficiency: A systematic review and meta-analysis.
We evaluated the efficacy, safety, adherence, quality of life (QoL) and cost-effectiveness of long-acting growth hormone (LAGH) vs daily growth hormone (GH) preparations in the treatment of growth hormone deficiency (GHD) in children. Systematic searches were performed in PubMed, Embase and Web of Science up to July 2022 on randomized and non-randomized studies involving children with GHD receiving LAGH as compared to daily GH. Meta-analyses for efficacy and safety were performed comparing different LAGH/daily GH formulations. From the initial 1393 records, we included 16 studies for efficacy and safety, 8 studies for adherence and 2 studies for QoL. No studies reporting cost-effectiveness were found. Pooled mean differences of mean annualized height velocity (cm/year) showed no difference between LAGH and daily GH: Eutropin Plus® vs Eutropin® [- 0.14 (-0.43, 0.15)], Eutropin Plus® vs Genotropin® [- 0.74 (-1.83, 0.34)], Jintrolong® vs Jintropin AQ® [0.05 (-0.54, 0.65)], Somatrogon vs Genotropin® [- 1.40 (-2.91, 0.10)], TransCon vs Genotropin® [0.93 (0.26, 1.61)]. Also, other efficacy and safety outcomes, QoL and adherence were comparable for LAGH and daily GH. Our results showed that, although most of the included studies had some concerns for risk of bias, regarding efficacy and safety all the LAGH formulations were similar to daily GH. Future high quality studies are needed to confirm these data. Adherence and QoL should be addressed from real-world data studies for both the mid and long term and in a larger population. Cost-effectiveness studies are needed to measure the economic impact of LAGH from the healthcare payer's perspective.
Topics: Humans; Child; Human Growth Hormone; Growth Hormone; Quality of Life; Cost-Benefit Analysis; Dwarfism, Pituitary; Hormone Replacement Therapy
PubMed: 37236413
DOI: 10.1016/j.phrs.2023.106805 -
Nutrients Nov 2023Iron deficiency (ID) is the most prevalent nutritional deficiency worldwide. Low levels of serum ferritin (SF) could affect the thyroid gland and its functioning. The... (Meta-Analysis)
Meta-Analysis Review
Iron deficiency (ID) is the most prevalent nutritional deficiency worldwide. Low levels of serum ferritin (SF) could affect the thyroid gland and its functioning. The purpose of this systematic review and meta-analysis is to summarize the main currently available evidence and analyze data on the relationship between ID and thyroid function. This study included all articles evaluating the relationship between ID and thyroid function. Quality assessment was performed using Cambridge Quality Checklists. The search strategy included the following combination of Medical Subjects Headings terms and keywords: "iron deficiency", "thyroid function", "thyroid disease", "thyroid dysfunction", and "hypothyroidism". A meta-analysis was performed to evaluate whether thyroid stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) levels differed between patients with ID and healthy controls without ID. For statistical comparison between cases and controls, the mean difference (MD) was calculated, and a subgroup analysis of pregnant and non-pregnant women was performed. Cochran's Q testing and heterogeneity indices () were used to assess statistical heterogeneity. Sensitivity analysis and publication bias analyses were also performed, both qualitatively and quantitatively. Finally, a meta-regression analysis was performed to evaluate the correlation between serum TSH or FT4 levels and SF in the study population. Ten cross-sectional studies were identified and reviewed. Patients with ID showed TSH (MD: -0.24 mIU/L; 95% CI -0.41, -0.07; = 100%, = 0.005), FT4 (MD: -1.18 pmol/L; 95% CI -1.43, -0.94; = 99%, < 0.000001), and FT3 (MD: -0.22 pmol/L; 95% CI -0.32, -0.12; = 99%, < 0.00001) levels that were significantly lower. Subgroup analysis confirmed significantly lower TSH, FT4, and FT3 levels in pregnant women. Non-pregnant women showed significantly lower serum FT4 and FT3 levels but no difference in TSH values. Meta-regression analysis showed that serum TSH and FT4 levels were positively correlated with SF levels. Our systematic review of the literature found that ID significantly increases the prevalence of thyroid autoantibody (anti-thyroglobulin antibodies and anti-thyroid peroxidase antibodies) positivity both individually and collectively. Studies currently published in the literature indicate a possible relationship between ID, thyroid function, and autoimmunity, especially in some patient groups. Data analysis shows that thyroid hormone levels are lower in patients with ID and, in particular, in pregnant women. Further studies are needed to understand the role played by iron in thyroid metabolism.
Topics: Humans; Female; Pregnancy; Thyroxine; Thyroid Function Tests; Cross-Sectional Studies; Thyroid Hormones; Thyroid Diseases; Thyrotropin; Iron Deficiencies
PubMed: 38004184
DOI: 10.3390/nu15224790 -
The Lancet. Diabetes & Endocrinology Apr 2022Adequate maternal thyroid function is important for an uncomplicated pregnancy. Although multiple observational studies have evaluated the association between thyroid... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Adequate maternal thyroid function is important for an uncomplicated pregnancy. Although multiple observational studies have evaluated the association between thyroid dysfunction and hypertensive disorders of pregnancy, the methods and definitions of abnormalities in thyroid function tests were heterogeneous, and the results were conflicting. We aimed to examine the association between abnormalities in thyroid function tests and risk of gestational hypertension and pre-eclampsia.
METHODS
In this systematic review and meta-analysis of individual-participant data, we searched MEDLINE (Ovid), Embase, Scopus, and the Cochrane Database of Systematic Reviews from date of inception to Dec 27, 2019, for prospective cohort studies with data on maternal concentrations of thyroid-stimulating hormone (TSH), free thyroxine (FT), thyroid peroxidase (TPO) antibodies, individually or in combination, as well as on gestational hypertension, pre-eclampsia, or both. We issued open invitations to study authors to participate in the Consortium on Thyroid and Pregnancy and to share the individual-participant data. We excluded participants who had pre-existing thyroid disease or multifetal pregnancy, or were taking medications that affect thyroid function. The primary outcomes were documented gestational hypertension and pre-eclampsia. Individual-participant data were analysed using logistic mixed-effects regression models adjusting for maternal age, BMI, smoking, parity, ethnicity, and gestational age at blood sampling. The study protocol was registered with PROSPERO, CRD42019128585.
FINDINGS
We identified 1539 published studies, of which 33 cohorts met the inclusion criteria and 19 cohorts were included after the authors agreed to participate. Our study population comprised 46 528 pregnant women, of whom 39 826 (85·6%) women had sufficient data (TSH and FT concentrations and TPO antibody status) to be classified according to their thyroid function status. Of these women, 1275 (3·2%) had subclinical hypothyroidism, 933 (2·3%) had isolated hypothyroxinaemia, 619 (1·6%) had subclinical hyperthyroidism, and 337 (0·8%) had overt hyperthyroidism. Compared with euthyroidism, subclinical hypothyroidism was associated with a higher risk of pre-eclampsia (2·1% vs 3·6%; OR 1·53 [95% CI 1·09-2·15]). Subclinical hyperthyroidism, isolated hypothyroxinaemia, or TPO antibody positivity were not associated with gestational hypertension or pre-eclampsia. In continuous analyses, both a higher and a lower TSH concentration were associated with a higher risk of pre-eclampsia (p=0·0001). FT concentrations were not associated with the outcomes measured.
INTERPRETATION
Compared with euthyroidism, subclinical hypothyroidism during pregnancy was associated with a higher risk of pre-eclampsia. There was a U-shaped association of TSH with pre-eclampsia. These results quantify the risks of gestational hypertension or pre-eclampsia in women with thyroid function test abnormalities, adding to the total body of evidence on the risk of adverse maternal and fetal outcomes of thyroid dysfunction during pregnancy. These findings have potential implications for defining the optimal treatment target in women treated with levothyroxine during pregnancy, which needs to be assessed in future interventional studies.
FUNDING
Arkansas Biosciences Institute and Netherlands Organization for Scientific Research.
Topics: Female; Humans; Hypertension, Pregnancy-Induced; Hyperthyroidism; Hypothyroidism; Male; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Prospective Studies; Thyroid Diseases; Thyrotropin; Thyroxine
PubMed: 35255260
DOI: 10.1016/S2213-8587(22)00007-9 -
Advances in Therapy Sep 2023Achondroplasia is the most common form of skeletal dysplasia. Recent advances in therapeutic options have highlighted the need for understanding the burden and treatment... (Review)
Review
BACKGROUND
Achondroplasia is the most common form of skeletal dysplasia. Recent advances in therapeutic options have highlighted the need for understanding the burden and treatment landscape of the condition. This systematic literature review (SLR) aimed to identify health-related quality of life (HRQoL)/utilities, healthcare resource use (HCRU), costs, efficacy, safety and economic evaluation data in achondroplasia and to identify gaps in the research.
METHODS
Searches of MEDLINE, Embase, the University of York Centre for Reviews and Dissemination (CRD), the Cochrane Library and grey literature were performed. Articles were screened against pre-specified eligibility criteria by two individuals and study quality was assessed using published checklists. Additional targeted searches were conducted to identify management guidelines.
RESULTS
Fifty-nine unique studies were included. Results demonstrated a substantial HRQoL and HCRU/cost-related burden of achondroplasia on affected individuals and their families throughout their lifetimes, particularly in emotional wellbeing and hospitalisation costs and resource use. Vosoritide, growth hormone (GH) and limb lengthening all conferred benefits for height or growth velocity; however, the long-term effects of GH therapy were unclear, data for vosoritide were from a limited number of studies, and limb lengthening was associated with complications. Included management guidelines varied widely in their scope, with the first global effort to standardise achondroplasia management represented by the International Achondroplasia Consensus Statement published at the end of 2021. Current evidence gaps include a lack of utility and cost-effectiveness data for achondroplasia and its treatments.
CONCLUSIONS
This SLR provides a comprehensive overview of the current burden and treatment landscape for achondroplasia, along with areas where evidence is lacking. This review should be updated as new evidence becomes available on emerging therapies.
Topics: Humans; Quality of Life; Achondroplasia; Human Growth Hormone; Cost-Benefit Analysis
PubMed: 37382866
DOI: 10.1007/s12325-023-02549-3 -
The Cochrane Database of Systematic... Sep 2020Engorgement is the overfilling of breasts with milk, often occurring in the early days postpartum. It results in swollen, hard, painful breasts and may lead to premature...
BACKGROUND
Engorgement is the overfilling of breasts with milk, often occurring in the early days postpartum. It results in swollen, hard, painful breasts and may lead to premature cessation of breastfeeding, decreased milk production, cracked nipples and mastitis. Various treatments have been studied but little consistent evidence has been found on effective interventions.
OBJECTIVES
To determine the effectiveness and safety of different treatments for engorgement in breastfeeding women.
SEARCH METHODS
On 2 October 2019, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP), and reference lists of retrieved studies.
SELECTION CRITERIA
All types of randomised controlled trials and all forms of treatment for breast engorgement were eligible.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for eligibility, extracted data, conducted 'Risk of bias' assessment and assessed the certainty of evidence using GRADE.
MAIN RESULTS
For this udpate, we included 21 studies (2170 women randomised) conducted in a variety of settings. Six studies used individual breasts as the unit of analysis. Trials examined a range of interventions: cabbage leaves, various herbal compresses (ginger, cactus and aloe, hollyhock), massage (manual, electromechanical, Oketani), acupuncture, ultrasound, acupressure, scraping therapy, cold packs, and medical treatments (serrapeptase, protease, oxytocin). Due to heterogeneity, meta-analysis was not possible and data were reported from single trials. Certainty of evidence was downgraded for limitations in study design, imprecision and for inconsistency of effects. We report here findings from key comparisons. Cabbage leaf treatments compared to control For breast pain, cold cabbage leaves may be more effective than routine care (mean difference (MD) -1.03 points on 0-10 visual analogue scale (VAS), 95% confidence intervals (CI) -1.53 to -0.53; 152 women; very low-certainty evidence) or cold gel packs (-0.63 VAS points, 95% CI -1.09 to -0.17; 152 women; very low-certainty evidence), although the evidence is very uncertain. We are uncertain about cold cabbage leaves compared to room temperature cabbage leaves, room temperature cabbage leaves compared to hot water bag, and cabbage leaf extract cream compared to placebo cream because the CIs were wide and included no effect. For breast hardness, cold cabbage leaves may be more effective than routine care (MD -0.58 VAS points, 95% CI -0.82 to -0.34; 152 women; low-certainty evidence). We are uncertain about cold cabbage leaves compared to cold gel packs because the CIs were wide and included no effect. For breast engorgement, room temperature cabbage leaves may be more effective than a hot water bag (MD -1.16 points on 1-6 scale, 95% CI -1.36 to -0.96; 63 women; very low-certainty evidence). We are uncertain about cabbage leaf extract cream compared to placebo cream because the CIs were wide and included no effect. More women were satisfied with cold cabbage leaves than with routine care (risk ratio (RR) 1.42, 95% CI 1.22 to 1.64; 152 women; low certainty), or with cold gel packs (RR 1.23, 95% CI 1.10 to 1.38; 152 women; low-certainty evidence). We are uncertain if women breastfeed longer following treatment with cold cabbage leaves than routine care because CIs were wide and included no effect. Breast swelling and adverse events were not reported. Compress treatments compared to control For breast pain, herbal compress may be more effective than hot compress (MD -1.80 VAS points, 95% CI -2.07 to -1.53; 500 women; low-certainty evidence). Massage therapy plus cactus and aloe compress may be more effective than massage therapy alone (MD -1.27 VAS points, 95% CI -1.75 to -0.79; 100 women; low-certainty evidence). In a comparison of cactus and aloe compress to massage therapy, the CIs were wide and included no effect. For breast hardness, cactus and aloe cold compress may be more effective than massage (RR 0.66, 95% CI 0.51 to 0.87; 102 women; low-certainty evidence). Massage plus cactus and aloe cold compress may reduce the risk of breast hardness compared to massage alone (RR 0.38, 95% CI 0.25 to 0.58; 100 women; low-certainty evidence). We are uncertain about the effects of compress treatments on breast engorgement and cessation of breastfeeding because the certainty of evidence was very low. Among women receiving herbal compress treatment, 2/250 experienced skin irritation compared to 0/250 in the hot compress group (moderate-certainty evidence). Breast swelling and women's opinion of treatment were not reported. Medical treatments compared to placebo Protease may reduce breast pain (RR 0.17, 95% CI 0.04, 0.74; low-certainty evidence; 59 women) and breast swelling (RR 0.34, 95% CI 0.15 to 0.79; 59 women; low-certainty evidence), whereas serrapeptase may reduce the risk of engorgement compared to placebo (RR 0.36, 95% CI 0.14 to 0.88; 59 women; low-certainty evidence). We are uncertain if serrapeptase reduces breast pain or swelling, or if oxytocin reduces breast engorgement compared to placebo, because the CIs were wide and included no effect. No women experienced adverse events in any of the groups receiving serrapeptase, protease or placebo (low-certainty evidence). Breast induration/hardness, women's opinion of treatment and breastfeeding cessation were not reported. Cold gel packs compared to control For breast pain, we are uncertain about the effectiveness of cold gel packs compared to control treatments because the certainty of evidence was very low. For breast hardness, cold gel packs may be more effective than routine care (MD -0.34 points on 1-6 scale, 95% CI -0.60 to -0.08; 151 women; low-certainty evidence). It is uncertain if women breastfeed longer following cold gel pack treatment compared to routine care because the CIs were wide and included no effect. There may be little difference in women's satisfaction with cold gel packs compared to routine care (RR 1.17, 95% CI 0.97 to 1.40; 151 women; low-certainty evidence). Breast swelling, engorgement and adverse events were not reported.
AUTHORS' CONCLUSIONS
Although some interventions may be promising for the treatment of breast engorgement, such as cabbage leaves, cold gel packs, herbal compresses, and massage, the certainty of evidence is low and we cannot draw robust conclusions about their true effects. Future trials should aim to include larger sample sizes, using women - not individual breasts - as units of analysis.
Topics: Acupuncture Therapy; Brassica; Breast Diseases; Cryotherapy; Female; Humans; Lactation Disorders; Massage; Mastodynia; Oxytocin; Peptide Hydrolases; Phytotherapy; Plant Leaves; Pregnancy; Randomized Controlled Trials as Topic; Ultrasonic Therapy
PubMed: 32944940
DOI: 10.1002/14651858.CD006946.pub4 -
American Journal of Obstetrics and... Mar 2022Postpartum hemorrhage causes a quarter of global maternal deaths. The World Health Organization recommends oxytocin as the first line agent to prevent hemorrhage during... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Postpartum hemorrhage causes a quarter of global maternal deaths. The World Health Organization recommends oxytocin as the first line agent to prevent hemorrhage during cesarean delivery. However, some randomized controlled trials suggest that other uterotonics are superior.
OBJECTIVE
We conducted a network meta-analysis comparing the ability of pharmacologic agents to reduce blood loss and minimize the need for additional uterotonics during cesarean delivery.
DATA SOURCES
We searched the Cochrane Central Register of Controlled Trials, Embase, and MEDLINE databases from inception to May 2020.
STUDY ELIGIBILITY CRITERIA
We included randomized controlled trials that compared oxytocin, carbetocin, misoprostol, ergometrine, carboprost, or combinations of these in the prevention of postpartum hemorrhage during cesarean delivery.
METHODS
We performed a systematic review followed by an NMA in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Quality of the evidence was assessed with the Confidence in Network Meta-Analysis approach and Grading of Recommendations, Assessment, Development and Evaluations tool within the summary of findings table. Our primary outcomes were the estimated blood loss and need for additional uterotonics. Secondary outcomes included nausea and postpartum hemorrhage of >1000 mL. We performed sensitivity analyses to explore the influence of surgical context and oxytocin administration strategy.
RESULTS
A total of 46 studies with 7368 participants were included. Of those, 21 trials (6 agents and 3665 participants) formed the "estimated blood loss" network and, considering the treatment effects, certainty in the evidence, and surface under the cumulative ranking curve scores, carbetocin was assessed to probably be superior to oxytocin, but only in reducing the estimated blood loss by a clinically insignificant volume (54.83 mL; 95% confidence interval, 26.48-143.78). Misoprostol, ergometrine, and the combination of oxytocin and ergometrine were assessed to probably be inferior, whereas the combination of oxytocin and misoprostol was assessed to definitely be inferior to oxytocin. A total of 37 trials (8 agents and 6193 participants) formed the "additional uterotonic" network and, again, carbetocin was assessed to probably be superior to oxytocin, requiring additional uterotonics 185 (95% confidence interval, 130-218) fewer times per 1000 cases. Oxytocin plus misoprostol, oxytocin plus ergometrine, and misoprostol were assessed to probably be inferior, whereas carboprost, ergometrine, and the placebo were definitely inferior to oxytocin. For both primary outcomes, oxytocin administration strategies had a higher probability of being the best uterotonic, if initiated as a bolus.
CONCLUSION
Carbetocin is probably the most effective agent in reducing blood loss and the need for additional uterotonics. Oxytocin appears to be more effective when initiated as a bolus.
Topics: Carboprost; Ergonovine; Female; Humans; Misoprostol; Network Meta-Analysis; Oxytocics; Oxytocin; Postpartum Hemorrhage; Pregnancy
PubMed: 34534498
DOI: 10.1016/j.ajog.2021.08.060 -
The Journal of Clinical Endocrinology... Sep 2022Interpretation of thyroid function tests during pregnancy is limited by the generalizability of reference intervals between cohorts due to inconsistent methodology. (Meta-Analysis)
Meta-Analysis
CONTEXT
Interpretation of thyroid function tests during pregnancy is limited by the generalizability of reference intervals between cohorts due to inconsistent methodology.
OBJECTIVE
(1) To provide an overview of published reference intervals for thyrotropin (TSH) and free thyroxine (FT4) in pregnancy, (2) to assess the consequences of common methodological between-study differences by combining raw data from different cohorts.
METHODS
(1) Ovid MEDLINE, EMBASE, and Web of Science were searched until December 12, 2021. Studies were assessed in duplicate. (2) The individual participant data (IPD) meta-analysis was performed in participating cohorts in the Consortium on Thyroid and Pregnancy.
RESULTS
(1) Large between-study methodological differences were identified, 11 of 102 included studies were in accordance with current guidelines; (2) 22 cohorts involving 63 198 participants were included in the meta-analysis. Not excluding thyroid peroxidase antibody-positive participants led to a rise in the upper limits of TSH in all cohorts, especially in the first (mean +17.4%; range +1.6 to +30.3%) and second trimester (mean +9.8%; range +0.6 to +32.3%). The use of the 95th percentile led to considerable changes in upper limits, varying from -10.8% to -21.8% for TSH and -1.2% to -13.2% for FT4. All other additional exclusion criteria changed reference interval cut-offs by a maximum of 3.5%. Applying these findings to the 102 studies included in the systematic review, 48 studies could be used in a clinical setting.
CONCLUSION
We provide an overview of clinically relevant reference intervals for TSH and FT4 in pregnancy. The results of the meta-analysis indicate that future studies can adopt a simplified study setup without additional exclusion criteria.
Topics: Female; Humans; Iodide Peroxidase; Pregnancy; Reference Values; Thyroid Function Tests; Thyroid Gland; Thyrotropin; Thyroxine
PubMed: 35861700
DOI: 10.1210/clinem/dgac425