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Hepato-gastroenterology Sep 2014The use of pre-medication to improve visibility in gastrointestinal endoscopy has not been well addressed and remains controversial. The aim is to evaluate the effects... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND/AIMS
The use of pre-medication to improve visibility in gastrointestinal endoscopy has not been well addressed and remains controversial. The aim is to evaluate the effects of current pre-medication on endoscopic visualization.
METHODOLOGY
We made the overall strategies to search the different databases and assessed the quality of included studies according to the included and excluded standard. 1541 patients were treated with pre-medication.
RESULT
Ten prospective studies involving 1541 patients were included. There was improved visibility in patients treated with Simethicone (weighted mean difference -4.3; 95% confidence interval (CI), -4.94 to -3.67), compared to those who did not use Simethicone. In the Simethicone based regiment, administration of Pronase was noted with significantly improved visibility in the location of antrum and fundus, compared to those who did not use; however, administration of N-acetyl-L-cysteine could not lead to significantly improved visibility. Simethicone offered better visibility than N-acetyl-L-cysteine and Pronase alone.
CONCLUSIONS
There is improved visibility with pre-medication using Simethicone before esophagogastroduodenoscopy. In the Simethicone based regimen, administration of Pronase or N-acetyl-Lcysteine may be of little use in improving visibility. Based on the literature review, Simethicone dissolved in the water with the acceptably lowest ratio of 0.7 can still offer the good visibility but 30 mL of water should be avoided.
Topics: Acetylcysteine; Antifoaming Agents; Chi-Square Distribution; Endoscopy, Digestive System; Expectorants; Gastrointestinal Tract; Humans; Predictive Value of Tests; Premedication; Pronase; Simethicone
PubMed: 25436356
DOI: No ID Found -
BMC Health Services Research Jul 2016Suboptimal medication adherence is a significant threat to public health and resources. Devices that organise weekly doses by time and day are commonly used to reduce... (Review)
Review
BACKGROUND
Suboptimal medication adherence is a significant threat to public health and resources. Devices that organise weekly doses by time and day are commonly used to reduce unintentional non-adherence. However, there is limited evidence to support their use. This systematic review was conducted to evaluate current evidence for their efficacy, safety and costs.
METHODS
A pre-defined search of electronic databases from inception to January 2013 augmented with hand-searching was conducted. No limits were placed on publication date. Studies that compared organisation devices used by patients administering their own medication with standard medication packaging regardless of study design were eligible for inclusion. Studies that solely explored dispensing aspects of organisation devices were included whether or not they compared this to standard care. Screening of articles for inclusion and data extraction were completed independently by two reviewers with disagreements resolved by discussion. Outcomes were categorised into impact on health, medication adherence, healthcare utilisation, dispensing errors, supply procedures and costs. Risk of bias was also assessed.
RESULTS
Seventeen studies met the inclusion criteria. Health outcomes were investigated in seven studies of which three reported a positive effect associated with organisation devices. Medication adherence was reported in eight studies of which three reported a positive effect. Three studies reported health care utilisation data but overall results are inconclusive. No optimal dispensing or supply procedures were identified. Economic assessment of the impact of organisation devices is lacking. All studies were subject to a high risk of bias.
CONCLUSIONS
Evidence regarding the effects of medication organisation devices was limited, and the available evidence was susceptible to a high risk of bias. Organisation devices may help unintentional medication non-adherence and could improve health outcomes. There is a strong need for more studies that explore the impact of such devices on patients, and an equally pressing need for studies that explore the impacts on healthcare services.
TRIAL REGISTRATION
This systematic review is registered with PROSPERO (Registration number CRD42011001718 ).
Topics: Drug Packaging; Humans; Medication Adherence; Medication Errors; Pharmacies; Quality of Life; Reminder Systems; Treatment Outcome
PubMed: 27381448
DOI: 10.1186/s12913-016-1446-y -
Pharmacy (Basel, Switzerland) Apr 2022: The patronage of online pharmacies is rapidly growing, driven by the convenience and cheaper costs of purchasing prescription drugs electronically, especially under... (Review)
Review
: The patronage of online pharmacies is rapidly growing, driven by the convenience and cheaper costs of purchasing prescription drugs electronically, especially under the lockdown situation. However, there are issues regarding the quality of the prescription drugs sold online and the legitimacy of online pharmacies. The use of prescription drugs without the supervision of a licensed health care practitioner may potentially harm consumers. : This systematic review was conducted to improve the body of knowledge on three main aspects of online pharmacies: (1) type and characteristics of the online pharmacies selling drugs; (2) the quality of pharmaceutical drugs purchased online; and (3) the characteristics of consumers of online pharmacies. : Based on a pre-defined search strategy, PubMed and Scopus were utilised to search articles written in the English language published between January 2009 and February 2020. Studies focusing on the sale of prescription drugs were included. The terms used for the literature search were "online pharmacy", "internet pharmacy", "e-pharmacy", "prescription", "quality", "medication safety", and "counterfeit medicine". These terms were used alone and in combination with Boolean operators. The institutional webpages including the World Health Organization (WHO) and the United States Food and Drug Administration (USFDA) were also examined for any additional studies. No methodological limitations in terms of study design were applied. A standardised data collection form was used to compile the data. : Based on the inclusion and exclusion criteria, a total of 46 articles were eligible and included in the final analysis. There were 27 articles on types and characteristic of online pharmacies, 13 articles on the quality of prescription drugs sold from online pharmacies, and 11 articles on consumers purchasing prescription drugs from online pharmacies. Readers should note that five articles discussed both the types and characteristics of online pharmacies, and the quality of the drugs sold from the outlets. The response rate (products received out of the number of orders) ranged from 20% to 100%, whereas the proportion of consumers buying prescription drugs online ranged from 2.3% to 13%. Reasons for online purchase of prescription drugs include the difficulty of obtaining a prescription for certain medications such as opioid analgesics, cheaper cost, since the costs associated with seeing a physician to obtain a prescription are reduced, and the need to obtain drugs such as opioid analgesics and benzodiazepine for misuse. : Almost half of the online pharmacies are not properly regulated and fraudulent issues were uncovered. To address this issue, stricter regulation by World Health Organization and implementation should be carried out together with frequent monitoring of the licensure system and pharmacy verification on every online pharmacy, this would reduce the number of illegal or illegitimate online pharmacy.
PubMed: 35448701
DOI: 10.3390/pharmacy10020042 -
American Journal of Epidemiology Nov 2021Cancer is an important cause of childhood mortality, yet the etiology is largely unknown. A combination of pre- and postnatal factors is thought to be implicated,...
Cancer is an important cause of childhood mortality, yet the etiology is largely unknown. A combination of pre- and postnatal factors is thought to be implicated, including maternal medication use. We aimed to provide: 1) a systematic review of peer-reviewed publications on associations between maternal medication use and childhood cancer, with a focus on study design and methodology; and 2) suggestions for how to increase transparency, limit potential biases, and improve comparability in studies on maternal medication use and childhood cancer. We conducted a systematic search in the PubMed, Embase, Scopus, Cochrane, and Web of Science databases to June 8, 2020. Altogether, 112 studies were identified. The reviewed studies were heterogeneous in study design, exposure, and outcome classification. In 21 studies (19%), the outcome was any childhood cancer. Of the 91 papers that reported on specific types of cancer, 62% did not report the cancer classification system. The most frequently investigated medication groups were sex hormones (46 studies, excluding fertility medications), and antiinfectives (37 studies). Suggestions for strengthening future pharmacoepidemiologic studies on maternal medication use and childhood cancer relate to choice of cancer classification system, exposure windows, and methods for identification of, and control for, potential confounders.
Topics: Child; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Neoplasms; Pregnancy; Prenatal Exposure Delayed Effects
PubMed: 34017981
DOI: 10.1093/aje/kwab154 -
Frontiers in Neurology 2020Trimetazidine (TMZ) is a medication given to patients with stable coronary artery disease. While it is reportedly well-tolerated, there are increasing numbers of...
Trimetazidine (TMZ) is a medication given to patients with stable coronary artery disease. While it is reportedly well-tolerated, there are increasing numbers of reports of adverse events such as parkinsonism. The purpose of this study was to systematically review the currently available literature on TMZ-induced parkinsonism. A search of Scopus, MEDLINE, EMBASE, the Cochrane Library, the Health Technology Assessment Database, PubMed, Science Direct, and Google Scholar was conducted on or before November 7, 2019. The literature search included cohort studies, prospective and/or retrospective studies, meta-analysis, and other systematic reviews published as an original article, including abstracts and full texts. We included patients taking TMZ who developed one or more of the parkinsonian symptoms of bradykinesia, tremors, rigidity, and postural instability, where these symptoms improved after withdrawal of the said medication. There are currently five studies on TMZ use and associated parkinsonism. The literature included two case reports, one case series, and one retrospective and one prospective study. We found no results from randomized clinical trials. Overall, 88 patients developed TMZ-induced parkinsonism. Regression of parkinsonism was reported in all of the participants after withdrawal of TMZ. A total of 49 patients (55.7%) had complete regression of symptoms, while 39 patients (44.3%) had significant reduction of symptoms. The duration between TMZ (dose, 60-80 mg/day) intake and onset of symptoms ranged from 4 months to 20 years. The most commonly reported extrapyramidal symptoms were akinesia, rigidity, postural disturbances, and gait disorders, which were usually mild and symmetric. The current literature suggests that TMZ can induce parkinsonism that is reversible with drug withdrawal. It is warranted to examine patients, especially the elderly, on TMZ for parkinsonian symptoms and those with pre-existing neurodegenerative diseases. Further studies are needed to assess the risk-benefit ratio of this drug, especially in the elderly age group.
PubMed: 32158422
DOI: 10.3389/fneur.2020.00044 -
Frontiers in Immunology 2023To systematically compare the efficacy and safety of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) in children with allergic rhinitis (AR). (Meta-Analysis)
Meta-Analysis
AIM
To systematically compare the efficacy and safety of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) in children with allergic rhinitis (AR).
METHODS
PubMed, Embase, Cochrane Library, and Web of Science were searched from inception to March 2, 2023. Outcomes included symptom scores (SSs), medication scores (MSs), symptom and medication scores (SMSs), new sensitizations, development of asthma, improvement, and treatment-related adverse events (TRAEs). The quality of the included studies was assessed by the modified Jadad scale and Newcastle-Ottawa scale (NOS). Meta-regression was carried out to explore the source of heterogeneity. Subgroup analysis was further conducted in terms of study design [randomized controlled trials (RCTs), cohort studies], allergen [house dust mites (HDMs), grass pollen], treatment duration (≥ 24, 12-23 or < 12 months), allergen immunotherapy (AIT) modality (drops or tablets), and AIT protocol [continuous, pre-seasonal, co-seasonal, or after the grass pollen season (GPS)]. Sensitivity analysis was conducted for all outcomes. A Bayesian framework and a Monte Carlo Markov Chain (MCMC) model were developed for indirect comparison.
RESULTS
Totally 50 studies with 10813 AR children were included, with 4122 treated with SLIT, 1852 treated with SCIT, and 4839 treated with non-SLIT or non-SCIT therapy. For direct comparison, the SLIT group had a similar SS to the SCIT group [pooled standardized mean difference (SMD): 0.41, 95% confidence interval (CI): -0.46, 1.28, = 0.353]. Comparable MSs were observed in the SLIT and SCIT groups (pooled SMD: 0.82, 95%CI: -0.88, 2.53, = 0.344). For indirect comparison, no significant differences were found in SSs (pooled SMD: 1.20, 95% credibility interval (CrI): -1.70, 4.10), MSs (pooled SMD: 0.57, 95%CrI: -1.20, 2.30), SMSs (pooled SMD: 1.80, 95%CrI: -0.005, 3.60), new sensitizations [pooled relative risk (RR): 0.34, 95%CrI: 0.03, 3.58], and development of asthma (pooled RR: 0.68, 95%CrI: 0.01, 26.33) between the SLIT and SCIT groups; the SLIT group illustrated a significantly lower incidence of TRAEs than the SCIT group (pooled RR: 0.17, 95%CrI: 0.11, 0.26).
CONCLUSION
Considering both efficacy and safety, SLIT might be a more favorable AIT than SCIT in the treatment of pediatric AR, which may serve as a decision-making reference for clinicians.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO (CRD42023460693).
Topics: Child; Humans; Allergens; Asthma; Desensitization, Immunologic; Pollen; Rhinitis, Allergic; Immunotherapy; Sublingual Immunotherapy
PubMed: 38162647
DOI: 10.3389/fimmu.2023.1274241 -
The Canadian Journal of Hospital... 2018Pharmacists have been involved in the care of transplant recipients for several decades, and a growing body of literature shows the beneficial effects of clinical... (Review)
Review
BACKGROUND
Pharmacists have been involved in the care of transplant recipients for several decades, and a growing body of literature shows the beneficial effects of clinical pharmacist care on important outcomes for these patients.
OBJECTIVES
The primary objective was to describe the roles and impacts of pharmacists in a solid organ transplant setting. The secondary objective was to describe and rate the pharmacists' interventions.
DATA SOURCES
Three databases-PubMed, Embase, and Evidence-Based Medicine Reviews-were searched from January 1, 1990, to June 16, 2015.
STUDY SELECTION AND DATA EXTRACTION
All studies addressing the roles of pharmacists and the impacts of clinical pharmacy services on the care of solid organ transplant recipients were considered. Only studies providing a statistical analysis were included. Design, setting, sample size, patient characteristics, pharmacists' interventions, study bias, and outcomes were extracted for analysis.
DATA SYNTHESIS
Four randomized controlled trials, 4 cohort studies, 3 pre-post studies, and 1 quasi-randomized controlled trial were included in the review, representing a total of 1837 patients. Of the 12 studies included, 8 specifically focused on renal transplant, and 1 each focused on liver, lung, abdominal organ, and general solid organ transplant. The pivotal pharmacist activities leading to the main patient outcomes were medication counselling ( = 8 studies), medication reconciliation ( = 5), and reviewing and optimizing drug therapy ( = 3). Improvements to medication adherence ( = 6 studies), morbidity ( = 4), costs ( = 2), and medication errors ( = 2) were reported.
CONCLUSION
Currently available evidence suggests that pharmacists can improve patient outcomes in the solid organ transplant setting. Adherence, morbidity, costs, and medication errors were identified as the main outcomes that were improved by pharmaceutical interventions. Transplant programs need to invest more in this resource.
PubMed: 30401999
DOI: No ID Found -
Journal of Psychosomatic Research Oct 2021Inadequate medication adherence is a significant limitation for achieving optimal health outcomes across chronic health conditions. Mindfulness-based interventions... (Review)
Review
OBJECTIVE
Inadequate medication adherence is a significant limitation for achieving optimal health outcomes across chronic health conditions. Mindfulness-based interventions (MBIs) have been increasingly applied to promote medical regimen adherence as MBIs have been shown to improve patient-level barriers to adherence (i.e., depressive symptoms, cognitive impairment, stress). The purpose of this review is to investigate the state of research regarding MBIs targeting medication adherence in chronic illnesses and to identify evidence gaps to inform future studies.
METHODS
The search reviewed 5 databases (e.g., PubMed, PsycINFO, Embase, CINAHL, Proquest Thesis/Dissertations) to identify trials that quantitatively evaluated the effect of MBIs on medication adherence. Study abstracts and full texts were screened identifying eligible studies, and findings were summarized using a narrative synthesis.
RESULTS
A total of 497 studies were reviewed; 41 were eligible for full text review and 9 were included in narrative synthesis: seven were RCTs and two were pre-post designs. Study quality varied, with five rated moderate or high risk for bias. Clinical populations tested included living with HIV (k = 3), cardiovascular disease (k = 3), psychological disorders (k = 2), and men who underwent a radical prostatectomy (k = 1). Four studies found significant improvements in medication adherence, however only two of these studies had low risk of bias.
CONCLUSIONS
Research on MBI's for medication adherence is developing, but the effectiveness of MBIs remains unclear due to the nascent stage of evidence and methodological limitations of existing studies. Researchers should prioritize rigorous experimental designs, theory-driven investigations of behavioral mechanisms, and the use of objective measurements of adherence.
Topics: Bias; Cardiovascular Diseases; Chronic Disease; Humans; Male; Medication Adherence; Mindfulness
PubMed: 34332271
DOI: 10.1016/j.jpsychores.2021.110585 -
The Cochrane Database of Systematic... Aug 2020Metformin has been proposed as possibly a safer and more effective long-term treatment than the oral contraceptive pill (OCP) in women with polycystic ovary syndrome... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Metformin has been proposed as possibly a safer and more effective long-term treatment than the oral contraceptive pill (OCP) in women with polycystic ovary syndrome (PCOS). It is important to directly compare the efficacy and safety of metformin versus OCP in the long-term treatment of women with PCOS. This is an update of a Cochrane Review comparing insulin sensitising agents with the OCP and only includes studies on metformin.
OBJECTIVES
To assess the effectiveness and safety of metformin versus the OCP (alone or in combination) in improving clinical, hormonal, and metabolic features of PCOS.
SEARCH METHODS
In August 2019 we searched the Cochrane Gynaecology and Fertility Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and CINAHL, the trial registers, handsearched references of the identified articles, and contacted experts in the field to identify additional studies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of the use of metformin versus the OCP (alone or in combination) for women with PCOS.
DATA COLLECTION AND ANALYSIS
We used standard methods recommended by Cochrane. The primary review outcomes were the clinical parameters of hirsutism and adverse events, both severe (requiring stopping of medication), and minor. In the presence of substantial heterogeneity (I statistic > 50), which could be explained by pre-specified subgroup analyses on the basis of BMI, we reported the subgroups separately.
MAIN RESULTS
This is a substantive update. We identified 38 additional studies. We included 44 RCTs (2253 women), which comprised 39 RCTs on adult women (2047 women) and five RCTs on adolescent women (206 women). Evidence quality ranged from very low to low. The main limitations were risk of bias, imprecision and inconsistency. Metformin versus the OCP In adult women, we are uncertain of the effect of metformin compared to the OCP on hirsutism in subgroup body mass index (BMI) < 25 kg/m (mean difference (MD) 0.38, 95% confidence interval (CI) -0.44 to 1.19, 3 RCTs, n = 134, I = 50%, very low-quality evidence) and subgroup BMI > 30 kg/m (MD -0.38, 95% CI -1.93 to 1.17; 2 RCTs, n = 85, I = 34%, low-quality evidence). Metformin may be less effective in improving hirsutism compared to the OCP in the subgroup BMI 25 kg/m to 30 kg/m (MD 1.92, 95% CI 1.21 to 2.64, 5 RCTs, n = 254, I = 0%, low-quality evidence). Metformin may increase severe gastro-intestinal adverse events rate compared to the OCP (Peto odds ratio (OR) 6.42, 95% CI 2.98 to 13.84, 11 RCTs, n = 602, I = 0%, low-quality evidence). Metformin may decrease the incidence of severe other adverse events compared to the OCP (Peto OR 0.20, 95% CI 0.09 to 0.44, 8 RCTs, n = 363, I = 0%, low-quality evidence). There were no trials reporting on minor adverse events. In adolescents, we are uncertain whether there is a difference between Metformin and the OCP, on hirsutism and adverse events. Metformin versus metformin combined with the OCP In adult women, metformin may be less effective in improving hirsutism compared to Metformin combined with the OCP (MD 1.36, 95% CI 0.62 to 2.11, 3 RCTs, n = 135, I= 9%, low-quality evidence). We are uncertain if there was a difference between metformin and metformin combined with the OCP for severe gastro-intestinal adverse events (OR 0.74, 95% CI 0.21 to 2.53, 3 RCTs, n = 171, I = 0%, low-quality evidence), or for severe other adverse events (OR 0.56, 95% CI 0.11 to 2.82, 2 RCTs, n = 109, I = 44%, low-quality evidence). There were no trials reporting on minor adverse events. In adolescents, there were no trials for this comparison. The OCP versus metformin combined with the OCP In adult women, the OCP may be less effective in improving hirsutism compared to metformin combined with the OCP (MD 0.54, 95% CI 0.20 to 0.89, 6 RCTs, n = 389, I= 1%, low-quality evidence). The OCP may decrease the incidence of severe gastro-intestinal adverse events compared to metformin combined with the OCP (OR 0.20, 95% CI 0.06 to 0.72, 5 RCTs, n = 228, I = 0%, low-quality evidence). We are uncertain if there is a difference between the OCP and metformin combined with the OCP for severe other adverse events (OR 1.61, 95% CI 0.49 to 5.37, 4 RCTs, n = 159, I = 12%, low-quality evidence). The OCP may decrease the incidence of minor (gastro-intestinal) adverse events compared to metformin combined with the OCP (OR 0.06, 95% CI 0.01 to 0.44, 2 RCTs, n = 98, I = 0%, low-quality evidence). In adolescents, we are uncertain whether there is a difference between the OCP, compared to metformin combined with the OCP, on hirsutism or adverse events.
AUTHORS' CONCLUSIONS
In adult women with PCOS, metformin may be less effective in improving hirsutism compared to the OCP in the subgroup BMI 25 kg/m to 30 kg/m but we are uncertain if there was a difference between metformin and the OCP in subgroups BMI < 25 kg/m and BMI > 30kg/m. Compared to the OCP, metformin may increase the incidence of severe gastro-intestinal adverse events and decrease the incidence of severe other adverse events with no trials reporting on minor adverse events. Either metformin alone or the OCP alone may be less effective in improving hirsutism compared to metformin combined with the OCP. We are uncertain whether there is a difference between the OCP alone and metformin alone compared to metformin combined with the OCP for severe or minor adverse events except for the OCP versus metformin combined with the OCP where the OCP may decrease the incidence of severe and minor gastro-intestinal adverse events. In adolescent women with PCOS, we are uncertain whether there is a difference between any of the comparisons for hirsutism and adverse events due to either no evidence or very low-quality evidence. Further large well-designed RCTs that stratify for BMI are needed to evaluate metformin versus the OCP and combinations in women with PCOS, in particular adolescent women.
Topics: Acne Vulgaris; Adolescent; Adult; Body Mass Index; Cardiovascular Diseases; Contraceptives, Oral, Combined; Drug Therapy, Combination; Endometrial Neoplasms; Female; Hirsutism; Humans; Hypoglycemic Agents; Menstruation Disturbances; Metformin; Polycystic Ovary Syndrome; Randomized Controlled Trials as Topic; Young Adult
PubMed: 32794179
DOI: 10.1002/14651858.CD005552.pub3 -
The Cochrane Database of Systematic... May 2020Aspirin and heparin are widely used as preventive strategy to reduce the high risk of recurrent pregnancy loss in women with antiphospholipid antibodies (aPL). This... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Aspirin and heparin are widely used as preventive strategy to reduce the high risk of recurrent pregnancy loss in women with antiphospholipid antibodies (aPL). This review supersedes a previous, out-of-date review that evaluated all potential therapies for preventing recurrent pregnancy loss in women with aPL. The current review focusses on a narrower scope because current clinical practice is restricted to using aspirin or heparins, or both for women with aPL in an attempt to reduce pregnancy complications.
OBJECTIVES
To assess the effects of aspirin or heparin, or both for improving pregnancy outcomes in women with persistent (on two separate occasions) aPL, either lupus anticoagulant (LAC), anticardiolipin (aCL) or aβ-glycoprotein-I antibodies (aβGPI) or a combination, and recurrent pregnancy loss (two or more, which do not have to be consecutive).
SEARCH METHODS
We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (3 June 2019), and reference lists of retrieved studies. Where necessary, we attempted to contact trial authors.
SELECTION CRITERIA
Randomised, cluster-randomised and quasi-randomised controlled trials that assess the effects of aspirin, heparin (either low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH]), or a combination of aspirin and heparin compared with no treatment, placebo or another, on pregnancy outcomes in women with persistent aPL and recurrent pregnancy loss were eligible. All treatment regimens were considered.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for inclusion criteria and risk of bias. Two review authors independently extracted data and checked them for accuracy and the certainty of the evidence was assessed using the GRADE approach.
MAIN RESULTS
Eleven studies (1672 women) met the inclusion criteria; nine randomised controlled trials and two quasi-RCTs. The studies were conducted in the USA, Canada, UK, China, New Zealand, Iraq and Egypt. One included trial involved 1015 women, all other included trials had considerably lower numbers of participants (i.e. 141 women or fewer). Some studies had high risk of selection and attrition bias, and many did not include sufficient information to judge the risk of reporting bias. Overall, the certainty of evidence is low to very low due to the small numbers of women in the studies and to the risk of bias. The dose and type of heparin and aspirin varied among studies. One study compared aspirin alone with placebo; no studies compared heparin alone with placebo and there were no trials that had a no treatment comparator arm during pregnancy; five studies explored the efficacy of heparin (either UFH or LMWH) combined with aspirin compared with aspirin alone; one trial compared LMWH with aspirin; two trials compared the combination of LMWH plus aspirin with the combination of UFH plus aspirin; two studies evaluated the combination of different doses of heparin combined with aspirin. All trials used aspirin at a low dose. Aspirin versus placebo We are very uncertain if aspirin has any effect on live birth compared to placebo (risk ratio (RR) 0.94, 95% confidence interval (CI) 0.71 to 1.25, 1 trial, 40 women, very low-certainty evidence). We are very uncertain if aspirin has any effect on the risk of pre-eclampsia, pregnancy loss, preterm delivery of a live infant, intrauterine growth restriction or adverse events in the child, compared to placebo. We are very uncertain if aspirin has any effect on adverse events (bleeding) in the mother compared with placebo (RR 1.29, 95% CI 0.60 to 2.77, 1 study, 40 women). The certainty of evidence for these outcomes is very low because of imprecision, due to the low numbers of women involved and the wide 95% CIs, and also because of risk of bias. Venous thromboembolism and arterial thromboembolism were not reported in the included studies. Heparin plus aspirin versus aspirin alone Heparin plus aspirin may increase the number of live births (RR 1.27, 95% CI 1.09 to 1.49, 5 studies, 1295 women, low-certainty evidence). We are uncertain if heparin plus aspirin has any effect on the risk of pre-eclampsia, preterm delivery of a live infant, or intrauterine growth restriction, compared with aspirin alone because of risk of bias and imprecision due to the low numbers of women involved and the wide 95% CIs. We are very uncertain if heparin plus aspirin has any effect on adverse events (bleeding) in the mother compared with aspirin alone (RR 1.65, 95% CI 0.19 to 14.03, 1 study, 31 women). No women in either the heparin plus aspirin group or the aspirin alone group had heparin-induced thrombocytopenia, allergic reactions, or venous or arterial thromboembolism. Similarly, no infants had congenital malformations. Heparin plus aspirin may reduce the risk of pregnancy loss (RR 0.48, 95% CI 0.32 to 0.71, 5 studies, 1295 women, low-certainty evidence). When comparing LMWH plus aspirin versus aspirin alone the pooled RR for live birth was 1.20 (95% CI 1.04 to 1.38, 3 trials, 1155 women). In the comparison of UFH plus aspirin versus aspirin alone, the RR for live birth was 1.74 (95% CI 1.28 to 2.35, 2 trials, 140 women).
AUTHORS' CONCLUSIONS
The combination of heparin (UFH or LMWH) plus aspirin during the course of pregnancy may increase live birth rate in women with persistent aPL when compared with aspirin treatment alone. The observed beneficial effect of heparin was driven by one large study in which LMWH plus aspirin was compared with aspirin alone. Adverse events were frequently not, or not uniformly, reported in the included studies. More research is needed in this area in order to further evaluate potential risks and benefits of this treatment strategy, especially among women with aPL and recurrent pregnancy loss, to gain consensus on the ideal prevention for recurrent pregnancy loss, based on a risk profile.
Topics: Abortion, Habitual; Antibodies, Anticardiolipin; Antibodies, Antiphospholipid; Anticoagulants; Aspirin; Bias; Drug Therapy, Combination; Female; Heparin; Heparin, Low-Molecular-Weight; Humans; Live Birth; Lupus Coagulation Inhibitor; Placebos; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Hematologic; Pregnancy Outcome; Randomized Controlled Trials as Topic; beta 2-Glycoprotein I
PubMed: 32358837
DOI: 10.1002/14651858.CD012852.pub2