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BMJ Clinical Evidence Apr 2011Preterm birth occurs in about 5% to 10% of all births in resource-rich countries, but in recent years the incidence seems to have increased in some countries,... (Review)
Review
INTRODUCTION
Preterm birth occurs in about 5% to 10% of all births in resource-rich countries, but in recent years the incidence seems to have increased in some countries, particularly in the USA. We found little reliable evidence for incidence in resource-poor countries. The rate in northwestern Ethiopia has been reported to vary from 11% to 22%, depending on the age group of mothers studied, and is highest in teenage mothers.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of preventive interventions in women at high risk of preterm delivery? What are the effects of interventions to improve neonatal outcome after preterm rupture of membranes? What are the effects of treatments to stop contractions in preterm labour? What are the effects of elective compared with selective caesarean delivery for women in preterm labour? What are the effects of interventions to improve neonatal outcome in preterm delivery? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 58 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review, we present information relating to the effectiveness and safety of the following interventions: amnioinfusion for preterm rupture of membranes, antenatal corticosteroids, antibiotic treatment, bed rest, beta-mimetics, calcium channel blockers, elective caesarean, enhanced antenatal care programmes, magnesium sulphate, oxytocin receptor antagonists (atosiban), progesterone, prophylactic cervical cerclage, prostaglandin inhibitors (e.g., indometacin), selective caesarean, and thyrotropin-releasing hormone (TRH) (plus corticosteroids).
Topics: Adrenal Cortex Hormones; Adrenergic beta-Agonists; Cerclage, Cervical; Humans; Infant, Newborn; Obstetric Labor, Premature; Premature Birth; Progesterone; Thyrotropin-Releasing Hormone
PubMed: 21463540
DOI: No ID Found -
International Journal of Molecular... Jun 2023Through a process termed , platelets cause thrombi to shrink and become more stable. After platelets are activated via inside-out signaling, glycoprotein αIIbβIII...
Through a process termed , platelets cause thrombi to shrink and become more stable. After platelets are activated via inside-out signaling, glycoprotein αIIbβIII binds to fibrinogen and initiates a cascade of intracellular signaling that ends in actin remodeling, which causes the platelet to change its shape. Clot retraction is also important for wound healing. Although the detailed molecular biology of clot retraction is only partially understood, various substances and physiological conditions modulate clot retraction. In this review, we describe some of the current literature pertaining to clot retraction modulators. In addition, we discuss compounds from , , and that diminish clot retraction and have numerous other health benefits. Caffeic acid and diindolylmethane, both common in plants and vegetables, likewise reduce clot retraction, as do all-trans retinoic acid (a vitamin A derivative), two MAP4K inhibitors, and the chemotherapeutic drug Dasatinib. Conversely, the endogenous anticoagulant Protein S (PS) and the matricellular protein secreted modular calcium-binding protein 1 (SMOC1) both enhance clot retraction. Most studies aiming to identify mechanisms of clot retraction modulators have focused on the increased phosphorylation of vasodilator-stimulated phosphoprotein and inositol 1,4,5-triphosphate receptor I and the decreased phosphorylation of various phospholipases (e.g., phospholipase A2 (PLA) and phosphatidylinositol-specific phospholipase Cγ2 (PLCγ), c-Jun N-terminal kinase, and (PI3Ks). One study focused on the decreased phosphorylation of Sarcoma Family Kinases (SFK), and others have focused on increased cAMP levels and the downregulation of inflammatory markers such as thromboxanes, including thromboxane A2 (TXA) and thromboxane B2 (TXB); prostaglandin A2 (PGE2); reactive oxygen species (ROS); and cyclooxygenase (COX) enzyme activity. Additionally, pregnancy, fibrinolysis, and the autoimmune condition systemic lupus erythematosus all seem to affect, or at least have some relation with, clot retraction. All the clot retraction modulators need in-depth study to explain these effects.
Topics: Blood Platelets; Clot Retraction; Phosphorylation; Platelet Aggregation; Signal Transduction
PubMed: 37445780
DOI: 10.3390/ijms241310602 -
European Journal of Translational... Sep 2022The aim of this study was to identify the efficacy of drug agents for pharmacological Treatment of Presbyopia. Published research papers were reviewed using the relevant...
The aim of this study was to identify the efficacy of drug agents for pharmacological Treatment of Presbyopia. Published research papers were reviewed using the relevant terms in PubMed, Science direct, Google scholar, Medline, Google patent, Ovid, Cochrane Database of Systematic Reviews, Scopus. In the initial search, 2270 records were obtained. By removing duplicate articles and all articles that did not meet the inclusion criteria or were inappropriate due to indirect relevance to the subject, 44 studies were selected. It should be noted that all studies had inclusion criteria. There are a number of topical pharmacological agents available for treating presbyopia such as FOV Tears and PresbiDrop. They consist of parasympathetic agent and non-steroidal anti-inflammatory drugs (NSAIDs), to contract the ciliary and pupil muscle and restore the accommodation. Another example of topical pharmacological agent is EV06. It is a lens-softening eye drop which can affect the rigid lens in presbyopia. Currently there is no pharmacological agent available to treat presbyopia. Although there are limited number of peer-reviewed articles available, the outcome for future agents under investigation are promising.
PubMed: 36121117
DOI: 10.4081/ejtm.2022.10781 -
Scientific Reports Mar 2023There is increasing evidence of sex differences in underlying mechanisms causing pain in preclinical models, and in clinical populations. There are also important...
There is increasing evidence of sex differences in underlying mechanisms causing pain in preclinical models, and in clinical populations. There are also important disconnects between clinical pain populations and the way preclinical pain studies are conducted. For instance, osteoarthritis pain more frequently affects women, but most preclinical studies have been conducted using males in animal models. The most widely used painkillers, nonsteroidal anti-inflammatory drugs (NSAIDs), act on the prostaglandin pathway by inhibiting cyclooxygenase (COX) enzymes. The purpose of this study was to analyze the preclinical and clinical literature on the role of prostaglandins and COX in inflammation and pain. We aimed to specifically identify studies that used both sexes and investigate whether any sex-differences in the action of prostaglandins and COX inhibition had been reported, either in clinical or preclinical studies. We conducted a PubMed search and identified 369 preclinical studies and 100 clinical studies that matched our inclusion/exclusion criteria. Our analysis shows that only 17% of preclinical studies on prostaglandins used both sexes and, out of those, only 19% analyzed or reported data separated by sex. In contrast, 79% of the clinical studies analyzed used both sexes. However, only 6% of those reported data separated by sex. Interestingly, 14 out of 15 preclinical studies and 5 out of 6 clinical studies that analyzed data separated by sex have identified sex-differences. This builds on the increasing evidence of sex-differences in prostaglandin signaling and the importance of sex as a biological variable in data analysis. The preclinical literature identifies a sex difference in prostaglandin D synthase (PTGDS) expression where it is higher in female than in male rodents in the nervous system. We experimentally validated that PTGDS expression is higher in female human dorsal root ganglia (DRG) neurons recovered from organ donors. Our semi-systematic literature review reveals a need for continued inclusivity of both male and female animals in prostaglandins studies and data analysis separated by sex in preclinical and clinical studies. Our finding of sex-differences in neuronal PTGDS expression in humans exemplifies the need for a more comprehensive understanding of how the prostaglandin system functions in the DRG in rodents and humans.
Topics: Animals; Female; Humans; Male; Cyclooxygenase 2; Pain; Prostaglandins; Sensory Receptor Cells; Sex Characteristics
PubMed: 36949072
DOI: 10.1038/s41598-023-31603-x -
BMJ (Clinical Research Ed.) Oct 2012To determine the most effective tocolytic agent at delaying delivery. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To determine the most effective tocolytic agent at delaying delivery.
DESIGN
Systematic review and network meta-analysis.
DATA SOURCES
Cochrane Central Register of Controlled Trials, Medline, Medline In-Process, Embase, and CINAHL up to 17 February 2012.
STUDY SELECTION
Randomised controlled trials of tocolytic therapy in women at risk of preterm delivery.
DATA EXTRACTION
At least two reviewers extracted data on study design, characteristics, number of participants, and outcomes reported (neonatal and maternal). A network meta-analysis was done using a random effects model with drug class effect. Two sensitivity analyses were carried out for the primary outcome; restricted to studies at low risk of bias and restricted to studies excluding women at high risk of preterm delivery (those with multiple gestation and ruptured membranes).
RESULTS
Of the 3263 titles initially identified, 95 randomized controlled trials of tocolytic therapy were reviewed. Compared with placebo, the probability of delivery being delayed by 48 hours was highest with prostaglandin inhibitors (odds ratio 5.39, 95% credible interval 2.14 to 12.34) followed by magnesium sulfate (2.76, 1.58 to 4.94), calcium channel blockers (2.71, 1.17 to 5.91), beta mimetics (2.41, 1.27 to 4.55), and the oxytocin receptor blocker atosiban (2.02, 1.10 to 3.80). No class of tocolytic was significantly superior to placebo in reducing neonatal respiratory distress syndrome. Compared with placebo, side effects requiring a change of medication were significantly higher for beta mimetics (22.68, 7.51 to 73.67), magnesium sulfate (8.15, 2.47 to 27.70), and calcium channel blockers (3.80, 1.02 to 16.92). Prostaglandin inhibitors and calcium channel blockers were the tocolytics with the best probability of being ranked in the top three medication classes for the outcomes of 48 hour delay in delivery, respiratory distress syndrome, neonatal mortality, and maternal side effects (all cause).
CONCLUSIONS
Prostaglandin inhibitors and calcium channel blockers had the highest probability of delaying delivery and improving neonatal and maternal outcomes.
Topics: Calcium Channel Blockers; Female; Humans; Magnesium Sulfate; Obstetric Labor, Premature; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Prostaglandin Antagonists; Randomized Controlled Trials as Topic; Time Factors; Tocolysis; Tocolytic Agents; Treatment Outcome; Vasotocin
PubMed: 23048010
DOI: 10.1136/bmj.e6226 -
Respiratory Medicine May 2012Use of endothelin receptor antagonists (ERA), phosphodiesterase type-5 (PDE-5) inhibitors and prostaglandin analogues has resulted in improved outcomes in idiopathic... (Review)
Review
BACKGROUND
Use of endothelin receptor antagonists (ERA), phosphodiesterase type-5 (PDE-5) inhibitors and prostaglandin analogues has resulted in improved outcomes in idiopathic pulmonary arterial hypertension (IPAH) and systemic sclerosis-associated PAH (SSc-PAH) patients. However, patients often deteriorate on monotherapy. The objective of this study is to evaluate the effect of dual therapy on outcomes in IPAH and SSc-PAH.
METHODS
A systematic review of MEDLINE (1950-2011), EMBASE (1980-2011) and CINAHL (inception-2011) was conducted to identify studies that evaluated the effect of any dual combination of ERA, PDE-5 inhibitors or prostaglandin analogues on 6-min walk distance (6MWD), functional class (FC), haemodynamics, quality-of-life (QoL) or time-to-clinical-worsening in IPAH or SSc-PAH. A standardized form was used to abstract design, sample size, aetiology, outcome and treatment effect.
RESULTS
Twenty-six observational studies and 6 randomized trials were identified. Using combination PDE-5 inhibitor and prostaglandin analogues, 6/7 studies reported improvement in 6MWD, 6/8 studies reported improvement in FC, 6/6 studies reported improvement in haemodynamics and 1 trial demonstrated improvement in QoL and time-to-clinical-worsening. Using combination ERA and prostaglandin analogues, 4/6 studies and 1 trial reported improvement in 6MWD, 3/3 studies and 1 trial reported improvement in FC, 4/5 studies and 1 trial reported improvement in PAP. Using combination ERA and PDE-5 inhibitor, 4/7 studies reported an improvement in 6MWD, and 2/6 report improvement in FC.
CONCLUSION
The evidence suggests a beneficial effect of dual therapy in IPAH and SSc-PAH, particularly those who are deteriorating on monotherapy. Research should focus on subsets of patients to identify the optimal timing and combination of dual therapy.
Topics: Antihypertensive Agents; Drug Therapy, Combination; Endothelin Receptor Antagonists; Humans; Hypertension, Pulmonary; Phosphodiesterase 5 Inhibitors; Prostaglandins, Synthetic; Scleroderma, Systemic; Treatment Outcome
PubMed: 22366298
DOI: 10.1016/j.rmed.2011.12.018 -
Evidence-based Complementary and... 2019Despite the wide use of acupuncture for the management of visceral pain and the growing interest in the pathophysiology of visceral pain, there is no conclusive... (Review)
Review
BACKGROUND/AIMS
Despite the wide use of acupuncture for the management of visceral pain and the growing interest in the pathophysiology of visceral pain, there is no conclusive elucidation of the mechanisms behind the effects of acupuncture on visceral pain. This systematic review aims to provide an integrative understanding of the treatment mechanism of acupuncture for visceral pain.
METHODS
Electronic and hand searches were conducted to identify studies that involved visceral pain and acupuncture.
RESULTS
We retrieved 192 articles, out of which 46 studies were included in our review. The results of our review demonstrated that visceral pain behaviors were significantly alleviated in response to acupuncture treatment in groups treated with this intervention compared to in sham acupuncture or no-treatment groups. Changes in the concentrations of -endorphin, epinephrine, cortisol, and prostaglandin E2 in plasma, the levels of c-Fos, substance P, corticotropin-releasing hormone, P2X3, acetylcholinesterase (AchE), N-methyl-D-aspartate (NMDA) receptors, and serotonin in the gut/spinal cord, and the neuronal activity of the thalamus were associated with acupuncture treatment in visceral pain.
CONCLUSIONS
Acupuncture reduced visceral pain behavior and induced significant changes in neuronal activity as well as in the levels of pain/inflammation-related cytokines and neurotransmitters in the brain-gut axis. Further researches on the thalamus and on a standard animal model are warranted to improve our knowledge on the mechanism of acupuncture that facilitates visceral pain modulation.
PubMed: 31186654
DOI: 10.1155/2019/1304152 -
Inflammation Research : Official... Mar 2016A systematic review of all literature was done to assess the ability of the progestin dienogest (DNG) to influence the inflammatory response of endometriotic cells. (Review)
Review
OBJECTIVE AND DESIGN
A systematic review of all literature was done to assess the ability of the progestin dienogest (DNG) to influence the inflammatory response of endometriotic cells.
MAIN OUTCOME MEASURES
In vitro and in vivo studies report an influence of DNG on the inflammatory response in eutopic or ectopic endometrial tissue (animal or human).
RESULTS
After strict inclusion criteria were satisfied, 15 studies were identified that reported a DNG influence on the inflammatory response in endometrial tissue. These studies identified a modulation of prostaglandin (PG) production and metabolism (PGE2, PGE2 synthase, cyclo-oxygenase-2 and microsomal PGE synthase-1), pro-inflammatory cytokine and chemokine production [interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor-α, monocyte chemoattractant protein-1 and stromal cell-derived factor-1], growth factor biosynthesis (vascular endothelial growth factor and nerve growth factor) and signaling kinases, responsible for the control of inflammation. Evidence supports a progesterone receptor-mediated inhibition of the inflammatory response in PR-expressing epithelial cells. It also indicated that DNG inhibited the inflammatory response in stromal cells, however, whether this was via a PR-mediated mechanism is not clear.
CONCLUSIONS
DNG has a significant effect on the inflammatory microenvironment of endometriotic lesions that may contribute to its clinical efficacy. A better understanding of the specific anti-inflammatory activity of DNG and whether this contributes to its clinical efficacy can help develop treatments that focus on the inhibition of inflammation while minimizing hormonal modulation.
Topics: Animals; Cytokines; Endometriosis; Epithelial Cells; Female; Hormone Antagonists; Humans; Immunologic Factors; Intercellular Signaling Peptides and Proteins; Nandrolone; Prostaglandins; Stromal Cells
PubMed: 26650031
DOI: 10.1007/s00011-015-0909-7 -
Singapore Medical Journal May 2006Spontaneous preterm labour and delivery accounts for approximately one-third of preterm births, which is the predominant cause of perinatal mortality and morbidity. This... (Review)
Review
Spontaneous preterm labour and delivery accounts for approximately one-third of preterm births, which is the predominant cause of perinatal mortality and morbidity. This review aims to evaluate the evidence on the benefits and harms of five classes of tocolytic therapy, namely: betamimetics, calcium channel blockers, magnesium, non-steroidal anti-inflammatory agents, and atosiban. We performed a systematic review of the effectiveness of tocolytics to stop uterine contractions (first-line therapy). Reports of randomised controlled trials from searches of MEDLINE, bibliographies of review articles, Cochrane Collaboration and its Pregnancy and Childbirth Review Group between 1966 and 2003 were identified, using the search terms "randomised controlled trial" (RCT), "preterm labor", "tocolysis", "betamimetics", "ritodrine", "prostaglandin synthetase inhibitors", "indomethacin", "calcium channel blockers", "nifedipine", "oxytocin receptor blockers", "atosiban", and "magnesium sulphate". Studies on women with preterm labour comparing the effects of a tocolytic with a placebo or no treatment that met our inclusion criteria, were included. To our knowledge, the trials were conducted mainly before 1999 and there were no placebo-controlled trials after that. Of the 86 articles identified and evaluated, 14 first-line studies met more stringent requirements for meta-analyses. Tocolytics were associated with significant decreases in the odds of delivery within 24 hours (odds-ratio [OR] 0.54, 95 percent confidence interval [CI] 0.32-0.91) and 48 hours (OR 0.47, 95 percent CI 0.30-0.75). These effects were significant for beta-agonists, atosiban and indomethacin, but not magnesium sulphate. Maternal side-effects significantly associated with betamimetics were pulmonary oedema, cardiac arrhthymias and hypokalaemia. Although calcium antagonists have not been evaluated against placebo, comparative trials with beta-agonists have shown more favourable neonatal outcomes and better prolongation of gestation. In conclusion, the management of threatened preterm labour with first-line tocolytic therapy can prolong gestation. However, the time gained in-utero need to be optimised. There is no clear first-line tocolytic agent. The use of tocolytic agents should be individualised and based on maternal condition, potential side-effects and gestational age.
Topics: Female; Humans; Obstetric Labor, Premature; Pregnancy; Pregnancy Outcome; Time Factors; Tocolysis; Tocolytic Agents
PubMed: 16645683
DOI: No ID Found -
The Cochrane Database of Systematic... Jan 2016Oxytocin and prostaglandin are hormones responsible for uterine contraction during the third stage of labour. Receptors in the uterine muscles are stimulated by... (Review)
Review
BACKGROUND
Oxytocin and prostaglandin are hormones responsible for uterine contraction during the third stage of labour. Receptors in the uterine muscles are stimulated by exogenous or endogenous oxytocin leading to uterine contractions. Nipple stimulation or breastfeeding are stimuli that can lead to the secretion of oxytocin and consequent uterine contractions. Consequently, uterine contractions can reduce bleeding during the third stage of labour.
OBJECTIVES
To investigate the effects of breastfeeding or nipple stimulation on postpartum haemorrhage (PPH) during the third stage of labour.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (15 July 2015) and reference lists of retrieved studies.
SELECTION CRITERIA
Randomised and quasi-randomised controlled trials comparing breast stimulation, breastfeeding or suckling for PPH in the third stage of labour were selected for this review.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed studies for inclusion in terms of risk of bias and independently extracted data. Disagreements were resolved by a third review author.
MAIN RESULTS
We included four trials (4608 women), but only two studies contributed data to the review's analyses (n = 4472). The studies contributing data were assessed as of high risk of bias overall. One of these studies was cluster-randomised and conducted in a low-income country and the other study was carried out in a high-income country. All four included studies assessed blood loss in the third stage of labour. Birth attendants estimated blood loss in two trials. The third trial assessed the hematocrit level on the second day postpartum to determine the effect of the bleeding. The fourth study measured PPH ≥ 500 mL. Nipple stimulation versus no treatmentOne study (4385 women) compared the effect of suckling versus no treatment. Blood loss was not measured in 114 women (59 in control group and 55 in suckling group). After excluding twin pregnancies, stillbirths and neonatal deaths, the main analyses for this trial were performed on 4227 vaginal deliveries. In terms of maternal death or severe morbidity, one maternal death occurred in the suckling group due to retained placenta (risk ratio (RR) 3.03, 95% confidence interval (CI) 0.12 to 74.26; one study, participants = 4227; very low quality evidence); severe morbidity was not mentioned. Severe PPH (≥ 1000 mL) was not reported in this study.The incidence of PPH (≥ 500 mL) was similar in the suckling and no treatment groups (RR 0.95, 95% CI 0.77 to 1.16; one study, participants = 4227; moderate quality). There were no group differences between nipple stimulation and no treatment regarding blood loss in the third stage of labour (mean difference (MD) 2.00, 95% CI -7.39 to 11.39; one study, participants = 4227; low quality). The rates of retained placenta were similar (RR 1.01, 95% CI 0.14 to 7.16; one study, participants = 4227; very low quality evidence), as were perinatal deaths (RR 1.06, 95% CI 0.57 to 1.98; one study, participants = 4271; low quality), and maternal readmission to hospital (RR 1.01, 95% CI 0.14 to 7.16; one study, participants = 4227; very low quality). We downgraded the evidence for this comparison for risk of bias concerns in the one included trial (inappropriate analyses for cluster design) and for imprecision (wide CIs crossing the line of no difference and, for some outcomes, few events).Many maternal secondary outcomes (including side effects) were not reported. Similarly, most neonatal secondary outcomes were not reported. Nipple stimulation versus oxytocinAnother study compared the effect of nipple stimulation (via a breast pump) with oxytocin. Eighty-seven women were recruited but only 85 women were analysed. Severe PPH ≥ 1000 mL and maternal death or severe morbidity were not reported.There was no clear effect of nipple stimulation on blood loss (MD 15.00, 95% CI -24.50 to 54.50; one study, participants = 85; low quality evidence), or on postnatal anaemia compared to the oxytocin group (MD -0.40, 95% CI -2.22 to 1.42; one study, participants = 85; low quality evidence). We downgraded evidence for this comparison due to risk of bias concerns in the one included trial (alternate allocation) and for imprecision (wide CIs crossing the line of no difference and small sample size).Many maternal secondary outcomes (including side effects) were not reported, and none of this review's neonatal secondary outcomes were reported.
AUTHORS' CONCLUSIONS
None of the included studies reported one of this review's primary outcomes: severe PPH ≥ 1000 mL. Only one study reported on maternal death or severe morbidity. There were limited secondary outcome data for maternal outcomes and very few secondary outcome data for neonatal outcomes.There was no clear differences between nipple stimulation (suckling) versus no treatment in relation to maternal death, the incidence of PPH (≥ 500 mL), blood loss in the third stage of labour, retained placenta, perinatal deaths or maternal readmission to hospital. Whilst these data are based on a single study with a reasonable sample size, the quality of these data are mostly low or very low.There is insufficient evidence to evaluate the effect of nipple stimulation for reducing postpartum haemorrhage during the third stage of labour and more evidence from high-quality studies is needed. Further high-quality studies should recruit adequate sample sizes, assess the impact of nipple stimulation compared to uterotonic agents such as syntometrine and oxytocin, and report on important outcomes such as those listed in this review.
Topics: Adult; Breast Feeding; Female; Hematocrit; Humans; Incidence; Labor Stage, Third; Nipples; Oxytocin; Physical Stimulation; Placenta, Retained; Postpartum Hemorrhage; Pregnancy; Randomized Controlled Trials as Topic
PubMed: 26816300
DOI: 10.1002/14651858.CD010845.pub2