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American Journal of Public Health Jan 2016Birth defects remain a significant source of worldwide morbidity and mortality. Strong scientific evidence shows that folic acid fortification of a region's food supply... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Birth defects remain a significant source of worldwide morbidity and mortality. Strong scientific evidence shows that folic acid fortification of a region's food supply leads to a decrease in spina bifida (a birth defect of the spine). Still, many countries around the world have yet to approve mandatory fortification through government legislation.
OBJECTIVES
We sought to perform a systematic review and meta-analysis of period prevalence of spina bifida by folic acid fortification status, geographic region, and study population.
SEARCH METHODS
An expert research librarian used terms related to neural tube defects and epidemiology from primary research from 1985 to 2010 to search in EMBASE and MEDLINE. We searched the reference lists of included articles and key review articles identified by experts.
SELECTION CRITERIA
Inclusion criteria included studies in English or French reporting on prevalence published between January 1985 and December 2010 that (1) were primary research, (2) were population-based, and (3) reported a point or period prevalence estimate of spina bifida (i.e., prevalence estimate with confidence intervals or case numerator and population denominator). Two independent reviewers screened titles and abstracts for eligible articles, then 2 authors screened full texts in duplicate for final inclusion. Disagreements were resolved through consensus or a third party.
DATA COLLECTION AND ANALYSIS
We followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses, or PRISMA, abstracting data related to case ascertainment, study population, folic acid fortification status, geographic region, and prevalence estimate independently and in duplicate. We extracted overall data and any subgroups reported by age, gender, time period, or type of spina bifida. We classified each period prevalence estimate as "mandatory" or "voluntary" folic acid fortification according to each country's folic acid fortification status at the time data were collected (as determined by a well-recognized fortification monitoring body, Food Fortification Initiative). We determined study quality on the basis of sample representativeness, standardization of data collection and birth defect assessment, and statistical analyses. We analyzed study-level period prevalence estimates by using a random effects model (α level of < 0.05) for all meta-analyses. We stratified pooled period prevalence estimates by birth population, fortification status, and continent.
RESULTS
Of 4078 studies identified, we included 179 studies in the systematic review and 123 in a meta-analysis. In studies of live births (LBs) alone, period prevalences of spina bifida were (1) lower in geographical regions with mandatory (33.86 per 100,000 LBs) versus voluntary (48.35 per 100,000 LBs) folic acid fortification, and (2) lower in studies of LBs, stillbirths, and terminations of pregnancy in regions with mandatory (35.22 per 100,000 LBs) versus voluntary (52.29 per 100,000 LBs) fortification. In LBs, stillbirths, and terminations of pregnancy studies, the lowest pooled prevalence estimate was in North America (38.70 per 100,000). Case ascertainment, surveillance methods, and reporting varied across these population-based studies.
CONCLUSIONS
Mandatory legislation enforcing folic acid fortification of the food supply lags behind the evidence, particularly in Asian and European countries. This extensive literature review shows that spina bifida is significantly more common in world regions without government legislation regulating full-coverage folic acid fortification of the food supply (i.e., Asia, Europe) and that mandatory folic acid fortification resulted in a lower prevalence of spina bifida regardless of the type of birth cohort. African data were scarce, but needed, as many African nations are beginning to adopt folic acid legislation.
Topics: Female; Folic Acid; Food, Fortified; Global Health; Humans; Pregnancy; Prevalence; Spinal Dysraphism; Vitamin B Complex
PubMed: 26562127
DOI: 10.2105/AJPH.2015.302902 -
The Cochrane Database of Systematic... Mar 2021Lupus erythematosus is an autoimmune disease with significant morbidity and mortality. Cutaneous disease in systemic lupus erythematosus (SLE) is common. Many...
BACKGROUND
Lupus erythematosus is an autoimmune disease with significant morbidity and mortality. Cutaneous disease in systemic lupus erythematosus (SLE) is common. Many interventions are used to treat SLE with varying efficacy, risks, and benefits.
OBJECTIVES
To assess the effects of interventions for cutaneous disease in SLE.
SEARCH METHODS
We searched the following databases up to June 2019: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, Wiley Interscience Online Library, and Biblioteca Virtual em Saude (Virtual Health Library). We updated our search in September 2020, but these results have not yet been fully incorporated.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of interventions for cutaneous disease in SLE compared with placebo, another intervention, no treatment, or different doses of the same intervention. We did not evaluate trials of cutaneous lupus in people without a diagnosis of SLE.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. Primary outcomes were complete and partial clinical response. Secondary outcomes included reduction (or change) in number of clinical flares; and severe and minor adverse events. We used GRADE to assess the quality of evidence.
MAIN RESULTS
Sixty-one RCTs, involving 11,232 participants, reported 43 different interventions. Trials predominantly included women from outpatient clinics; the mean age range of participants was 20 to 40 years. Twenty-five studies reported baseline severity, and 22 studies included participants with moderate to severe cutaneous lupus erythematosus (CLE); duration of CLE was not well reported. Studies were conducted mainly in multi-centre settings. Most often treatment duration was 12 months. Risk of bias was highest for the domain of reporting bias, followed by performance/detection bias. We identified too few studies for meta-analysis for most comparisons. We limited this abstract to main comparisons (all administered orally) and outcomes. We did not identify clinical trials of other commonly used treatments, such as topical corticosteroids, that reported complete or partial clinical response or numbers of clinical flares. Complete clinical response Studies comparing oral hydroxychloroquine against placebo did not report complete clinical response. Chloroquine may increase complete clinical response at 12 months' follow-up compared with placebo (absence of skin lesions) (risk ratio (RR) 1.57, 95% confidence interval (CI) 0.95 to 2.61; 1 study, 24 participants; low-quality evidence). There may be little to no difference between methotrexate and chloroquine in complete clinical response (skin rash resolution) at 6 months' follow-up (RR 1.13, 95% CI 0.84 to 1.50; 1 study, 25 participants; low-quality evidence). Methotrexate may be superior to placebo with regard to complete clinical response (absence of malar/discoid rash) at 6 months' follow-up (RR 3.57, 95% CI 1.63 to 7.84; 1 study, 41 participants; low-quality evidence). At 12 months' follow-up, there may be little to no difference between azathioprine and ciclosporin in complete clinical response (malar rash resolution) (RR 0.83, 95% CI 0.46 to 1.52; 1 study, 89 participants; low-quality evidence). Partial clinical response Partial clinical response was reported for only one key comparison: hydroxychloroquine may increase partial clinical response at 12 months compared to placebo, but the 95% CI indicates that hydroxychloroquine may make no difference or may decrease response (RR 7.00, 95% CI 0.41 to 120.16; 20 pregnant participants, 1 trial; low-quality evidence). Clinical flares Clinical flares were reported for only two key comparisons: hydroxychloroquine is probably superior to placebo at 6 months' follow-up for reducing clinical flares (RR 0.49, 95% CI 0.28 to 0.89; 1 study, 47 participants; moderate-quality evidence). At 12 months' follow-up, there may be no difference between methotrexate and placebo, but the 95% CI indicates there may be more or fewer flares with methotrexate (RR 0.77, 95% CI 0.32 to 1.83; 1 study, 86 participants; moderate-quality evidence). Adverse events Data for adverse events were limited and were inconsistently reported, but hydroxychloroquine, chloroquine, and methotrexate have well-documented adverse effects including gastrointestinal symptoms, liver problems, and retinopathy for hydroxychloroquine and chloroquine and teratogenicity during pregnancy for methotrexate.
AUTHORS' CONCLUSIONS
Evidence supports the commonly-used treatment hydroxychloroquine, and there is also evidence supporting chloroquine and methotrexate for treating cutaneous disease in SLE. Evidence is limited due to the small number of studies reporting key outcomes. Evidence for most key outcomes was low or moderate quality, meaning findings should be interpreted with caution. Head-to-head intervention trials designed to detect differences in efficacy between treatments for specific CLE subtypes are needed. Thirteen further trials are awaiting classification and have not yet been incorporated in this review; they may alter the review conclusions.
Topics: Age of Onset; Azathioprine; Bias; Biological Factors; Chloroquine; Cosmetic Techniques; Cyclosporine; Dermatologic Agents; Exanthema; Female; Humans; Hydroxychloroquine; Immunosuppressive Agents; Lupus Erythematosus, Cutaneous; Lupus Erythematosus, Systemic; Male; Medicine, Chinese Traditional; Methotrexate; Placebos; Quality of Life; Randomized Controlled Trials as Topic; Skin Diseases; Symptom Flare Up
PubMed: 33687069
DOI: 10.1002/14651858.CD007478.pub2 -
Taiwanese Journal of Obstetrics &... Mar 2020Due to the morbidity and mortality of mothers and fetuses developed by preeclampsia, preventive approaches have always been taken into account in high risk individuals....
Due to the morbidity and mortality of mothers and fetuses developed by preeclampsia, preventive approaches have always been taken into account in high risk individuals. Systematic review studies contribute to make a better decision about the results of such studies. Accordingly, this study strived to systematically study the factors effective in the prevention of preeclampsia. The MEDLINE, ISI Web of Science, PubMed, Scopus, Google Scholar, and Proquest databases were systematically reviewed between January 2000 and May 2019. The quality of the studies was analyzed using the CONSORT checklist. A study was conducted on 29 quality interventional studies; 28 of which were RCT type, and on various factors such as anticoagulants (heparin, enoxaparin, Dalteparin and Nadroparin), aspirin, paravastatin, nitric oxide, yoga, micronutrients Such as l-Arginine, Folic Acid, Vitamin E and C, Phytonutrient, Lycopene and Vitamin D alone or in combination with Calcium. The results of this study showed that low molecular weight heparin, enoxaparin, PETN, yoga, L arginine, folic acid, vitamin D prevented preeclampsia alone or combined with calcium.
Topics: Arginine; Calcium; Drug Therapy, Combination; Enoxaparin; Female; Folic Acid; Heparin, Low-Molecular-Weight; Humans; Pentaerythritol Tetranitrate; Pre-Eclampsia; Pregnancy; Prenatal Care; Vitamin D; Yoga
PubMed: 32127134
DOI: 10.1016/j.tjog.2020.01.002 -
The Cochrane Database of Systematic... Dec 2015It has been reported that neural tube defects (NTD) can be prevented with periconceptional folic acid supplementation. The effects of different doses, forms and schemes... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
It has been reported that neural tube defects (NTD) can be prevented with periconceptional folic acid supplementation. The effects of different doses, forms and schemes of folate supplementation for the prevention of other birth defects and maternal and infant outcomes are unclear.
OBJECTIVES
This review aims to examine whether periconceptional folate supplementation reduces the risk of neural tube and other congenital anomalies (including cleft palate) without causing adverse outcomes in mothers or babies. This is an update of a previously published Cochrane review on this topic.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 August 2015). Additionally, we searched the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (31 August 2015) and contacted relevant organisations to identify ongoing and unpublished studies.
SELECTION CRITERIA
We included all randomised or quasi-randomised trials evaluating the effect of periconceptional folate supplementation alone, or in combination with other vitamins and minerals, in women independent of age and parity.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed the eligibility of studies against the inclusion criteria, extracted data from included studies, checked data entry for accuracy and assessed the risk of bias of the included studies. We assessed the quality of the body of evidence using the GRADE approach.
MAIN RESULTS
Five trials involving 7391 women (2033 with a history of a pregnancy affected by a NTD and 5358 with no history of NTDs) were included. Four comparisons were made: 1) supplementation with any folate versus no intervention, placebo or other micronutrients without folate (five trials); 2) supplementation with folic acid alone versus no treatment or placebo (one trial); 3) supplementation with folate plus other micronutrients versus other micronutrients without folate (four trials); and 4) supplementation with folate plus other micronutrients versus the same other micronutrients without folate (two trials). The risk of bias of the trials was variable. Only one trial was considered to be at low risk of bias. The remaining studies lacked clarity regarding the randomisation method or whether the allocation to the intervention was concealed. All the participants were blinded to the intervention, though blinding was unclear for outcome assessors in the five trials.The results of the first comparison involving 6708 births with information on NTDs and other infant outcomes, show a protective effect of daily folic acid supplementation (alone or in combination with other vitamins and minerals) in preventing NTDs compared with no interventions/placebo or vitamins and minerals without folic acid (risk ratio (RR) 0.31, 95% confidence interval (CI) 0.17 to 0.58); five studies; 6708 births; high quality evidence). Only one study assessed the incidence of NTDs and showed no evidence of an effect (RR 0.07, 95% CI 0.00 to 1.32; 4862 births) although no events were found in the group that received folic acid. Folic acid had a significant protective effect for reoccurrence (RR 0.34, 95% CI 0.18 to 0.64); four studies; 1846 births). Subgroup analyses suggest that the positive effect of folic acid on NTD incidence and recurrence is not affected by the explored daily folic acid dosage (400 µg (0.4 mg) or higher) or whether folic acid is given alone or with other vitamins and minerals. These results are consistent across all four review comparisons.There is no evidence of any preventive or negative effects on cleft palate (RR 0.73, 95% CI 0.05 to 10.89; three studies; 5612 births; low quality evidence), cleft lip ((RR 0.79, 95% CI 0.14 to 4.36; three studies; 5612 births; low quality evidence), congenital cardiovascular defects (RR 0.57, 95% CI 0.24 to 1.33; three studies; 5612 births; low quality evidence), miscarriages (RR 1.10, 95% CI 0.94 to 1.28; five studies; 7391 pregnancies; moderate quality evidence) or any other birth defects (RR 0.94, 95% CI 0.53 to 1.66; three studies; 5612 births; low quality evidence). There were no included trials assessing the effects of this intervention on neonatal death, maternal blood folate or anaemia at term.
AUTHORS' CONCLUSIONS
Folic acid, alone or in combination with vitamins and minerals, prevents NTDs, but does not have a clear effect on other birth defects.
Topics: Dietary Supplements; Female; Folic Acid; Humans; Infant; Neural Tube Defects; Preconception Care; Pregnancy; Randomized Controlled Trials as Topic; Vitamin B Complex
PubMed: 26662928
DOI: 10.1002/14651858.CD007950.pub3 -
Medicine Dec 2021Ectopic pregnancy (EP) is a common cause of acute abdominal pain in the field of gynecology. Because the majority of women with EP are hemodynamically stable,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Ectopic pregnancy (EP) is a common cause of acute abdominal pain in the field of gynecology. Because the majority of women with EP are hemodynamically stable, non-surgical therapy is a viable option. The goal of this study was to determine the most effective non-surgical therapy for hemodynamically stable EP.
METHODS
We performed a systematic review and meta-analysis. We searched PubMed, LILACS, SciELO, CINAHL, Embase, and the Cochrane library in May 2020, with no starting date restrictions.Studies were restricted to randomized controlled trials, which were included if the target population contained women with tubal EP and the intervention was non-surgical management. The primary outcome measure was treatment success defined by a decrease in serum hCG to a level ranging from five mIU/mL to 50 mIU/mL. Secondary outcome measures were side effects, time needed to treat, number of injections and operative rate.
RESULTS
We conducted a meta-analysis of 15 studies that included 1573 women who were diagnosed with EP and managed non-surgically. There was no significant difference in treatment success in the matched groups; however, single-dose MTX was associated with fewer side effects than multiple-dose (relative risk 0.48, 95% confidence interval 0.28-0.80, P = .006) and two-dose therapies (relative risk 0.74, 95% confidence interval 0.55-1.00, P = .05).
CONCLUSIONS
We highly recommend that single-dose MTX without mifepristone be used first-line in patients who require conservative therapy due to the inherent negative effects of mifepristone. An EP woman with a low -hCG level that is falling or plateauing should receive expectant treatment to reduce adverse effects.
Topics: Adult; Female; Humans; Methotrexate; Mifepristone; Pregnancy; Pregnancy, Ectopic; Pregnancy, Tubal; Treatment Outcome
PubMed: 34918633
DOI: 10.1097/MD.0000000000027851 -
The Cochrane Database of Systematic... Mar 2019Multiple-micronutrient (MMN) deficiencies often coexist among women of reproductive age in low- and middle-income countries. They are exacerbated in pregnancy due to the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Multiple-micronutrient (MMN) deficiencies often coexist among women of reproductive age in low- and middle-income countries. They are exacerbated in pregnancy due to the increased demands of the developing fetus, leading to potentially adverse effects on the mother and baby. A consensus is yet to be reached regarding the replacement of iron and folic acid supplementation with MMNs. Since the last update of this Cochrane Review in 2017, evidence from several trials has become available. The findings of this review will be critical to inform policy on micronutrient supplementation in pregnancy.
OBJECTIVES
To evaluate the benefits of oral multiple-micronutrient supplementation during pregnancy on maternal, fetal and infant health outcomes.
SEARCH METHODS
For this 2018 update, on 23 February 2018 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. We also contacted experts in the field for additional and ongoing trials.
SELECTION CRITERIA
All prospective randomised controlled trials evaluating MMN supplementation with iron and folic acid during pregnancy and its effects on pregnancy outcomes were eligible, irrespective of language or the publication status of the trials. We included cluster-randomised trials, but excluded quasi-randomised trials. Trial reports that were published as abstracts were eligible.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. We assessed the quality of the evidence using the GRADE approach.
MAIN RESULTS
We identified 21 trials (involving 142,496 women) as eligible for inclusion in this review, but only 20 trials (involving 141,849 women) contributed data. Of these 20 trials, 19 were conducted in low- and middle-income countries and compared MMN supplements with iron and folic acid to iron, with or without folic acid. One trial conducted in the UK compared MMN supplementation with placebo. In total, eight trials were cluster-randomised.MMN with iron and folic acid versus iron, with or without folic acid (19 trials)MMN supplementation probably led to a slight reduction in preterm births (average risk ratio (RR) 0.95, 95% confidence interval (CI) 0.90 to 1.01; 18 trials, 91,425 participants; moderate-quality evidence), and babies considered small-for-gestational age (SGA) (average RR 0.92, 95% CI 0.88 to 0.97; 17 trials; 57,348 participants; moderate-quality evidence), though the CI for the pooled effect for preterm births just crossed the line of no effect. MMN reduced the number of newborn infants identified as low birthweight (LBW) (average RR 0.88, 95% CI 0.85 to 0.91; 18 trials, 68,801 participants; high-quality evidence). We did not observe any differences between groups for perinatal mortality (average RR 1.00, 95% CI 0.90 to 1.11; 15 trials, 63,922 participants; high-quality evidence). MMN supplementation led to slightly fewer stillbirths (average RR 0.95, 95% CI 0.86 to 1.04; 17 trials, 97,927 participants; high-quality evidence) but, again, the CI for the pooled effect just crossed the line of no effect. MMN supplementation did not have an important effect on neonatal mortality (average RR 1.00, 95% CI 0.89 to 1.12; 14 trials, 80,964 participants; high-quality evidence). We observed little or no difference between groups for the other maternal and pregnancy outcomes: maternal anaemia in the third trimester (average RR 1.04, 95% CI 0.94 to 1.15; 9 trials, 5912 participants), maternal mortality (average RR 1.06, 95% CI 0.72 to 1.54; 6 trials, 106,275 participants), miscarriage (average RR 0.99, 95% CI 0.94 to 1.04; 12 trials, 100,565 participants), delivery via a caesarean section (average RR 1.13, 95% CI 0.99 to 1.29; 5 trials, 12,836 participants), and congenital anomalies (average RR 1.34, 95% CI 0.25 to 7.12; 2 trials, 1958 participants). However, MMN supplementation probably led to a reduction in very preterm births (average RR 0.81, 95% CI 0.71 to 0.93; 4 trials, 37,701 participants). We were unable to assess a number of prespecified, clinically important outcomes due to insufficient or non-available data.When we assessed primary outcomes according to GRADE criteria, the quality of evidence for the review overall was moderate to high. We graded the following outcomes as high quality: LBW, perinatal mortality, stillbirth, and neonatal mortality. The outcomes of preterm birth and SGA we graded as moderate quality; both were downgraded for funnel plot asymmetry, indicating possible publication bias.We carried out sensitivity analyses excluding trials with high levels of sample attrition (> 20%). We found that results were consistent with the main analyses for all outcomes. We explored heterogeneity through subgroup analyses by maternal height, maternal body mass index (BMI), timing of supplementation, dose of iron, and MMN supplement formulation (UNIMMAP versus non-UNIMMAP). There was a greater reduction in preterm births for women with low BMI and among those who took non-UNIMMAP supplements. We also observed subgroup differences for maternal BMI and maternal height for SGA, indicating greater impact among women with greater BMI and height. Though we found that MMN supplementation made little or no difference to perinatal mortality, the analysis demonstrated substantial statistical heterogeneity. We explored this heterogeneity using subgroup analysis and found differences for timing of supplementation, whereby higher impact was observed with later initiation of supplementation. For all other subgroup analyses, the findings were inconclusive.MMN versus placebo (1 trial)A single trial in the UK found little or no important effect of MMN supplementation on preterm births, SGA, or LBW but did find a reduction in maternal anaemia in the third trimester (RR 0.66, 95% CI 0.51 to 0.85), when compared to placebo. This trial did not measure our other outcomes.
AUTHORS' CONCLUSIONS
Our findings suggest a positive impact of MMN supplementation with iron and folic acid on several birth outcomes. MMN supplementation in pregnancy led to a reduction in babies considered LBW, and probably led to a reduction in babies considered SGA. In addition, MMN probably reduced preterm births. No important benefits or harms of MMN supplementation were found for mortality outcomes (stillbirths, perinatal and neonatal mortality). These findings may provide some basis to guide the replacement of iron and folic acid supplements with MMN supplements for pregnant women residing in low- and middle-income countries.
Topics: Dietary Supplements; Drug Interactions; Female; Folic Acid; Humans; Infant, Newborn; Infant, Small for Gestational Age; Iron, Dietary; Micronutrients; Perinatal Mortality; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Premature Birth; Randomized Controlled Trials as Topic
PubMed: 30873598
DOI: 10.1002/14651858.CD004905.pub6 -
American Journal of Obstetrics and... Aug 2019To compare the treatment success and failure rates, as well as side effects and surgery rates, between methotrexate protocols. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To compare the treatment success and failure rates, as well as side effects and surgery rates, between methotrexate protocols.
DATA SOURCES
PubMed, Embase, and the Cochrane library searched up to July 2018.
STUDY ELIGIBILITY CRITERIA
Randomized controlled trials that compared women with ectopic pregnancies receiving the single-dose, two-dose, or multi-dose methotrexate protocols.
STUDY APPRAISAL AND SYNTHESIS METHODS
Odds of treatment success, treatment failure, side effects, and surgery for tubal rupture, as well as length of follow-up until treatment success, were compared using random and fixed effects meta-analysis. Sensitivity analyses compared treatment success in the groups with high human chorionic gonadatropin (hCG) values and a large adnexal mass, as defined by individual studies. The Cochrane Collaboration tool was used to assess risk of bias.
RESULTS
The 2-dose protocol was associated with higher treatment success compared to the single-dose protocol (odds ratio [OR], 1.84; 95% CI, 1.13, 3.00). The 2-dose protocol was more successful in women with high hCG (OR, 3.23; 95% CI, 1.53, 6.84) and in women with a large adnexal mass (OR, 2.93; 95% CI, 1.23, 6.9). The odds of surgery for tubal rupture were lower in the 2-dose protocol (OR, 0.65; 95% CI, 0.26, 1.63), but this was not statistically significant. The length of follow-up was 7.9 days shorter for the 2-dose protocol (95% CI, -12.2, -3.5). The odds of side effects were higher in the 2-dose protocol (OR, 1.53; 95% CI, 1.01, 2.30). Compared to the single-dose protocol, the multi-dose protocol was associated with a nonsignificant reduction in treatment failure (OR, 0.56; 95% CI, 0.28, 1.13) and a higher chance of side effects (OR, 2.10; 95% CI, 1.24, 3.54). The odds of surgery for tubal rupture (OR, 1.62; 95% CI, 0.41, 6.49) and time to follow-up (OR, -1.3; 95% CI, -5.4, 2.7) were similar.
CONCLUSION
The 2-dose methotrexate protocol is superior to the single-dose protocol for the treatment of ectopic pregnancy in terms of treatment success and time to success. Importantly, these findings hold true in patients thought to be at a lower likelihood of responding to medical management, such as those with higher hCGs and a large adnexal mass.
Topics: Abortifacient Agents, Nonsteroidal; Chorionic Gonadotropin; Dose-Response Relationship, Drug; Fallopian Tubes; Female; Humans; Methotrexate; Pregnancy; Pregnancy, Ectopic; Randomized Controlled Trials as Topic; Rupture
PubMed: 30629908
DOI: 10.1016/j.ajog.2019.01.002 -
The American Journal of Psychiatry Apr 2015Public health campaigns encouraging early help seeking have increased rates of mild cognitive impairment (MCI) diagnosis in Western countries, but we know little about... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Public health campaigns encouraging early help seeking have increased rates of mild cognitive impairment (MCI) diagnosis in Western countries, but we know little about how to treat or predict dementia outcomes in persons with the condition.
METHOD
The authors searched electronic databases and references for longitudinal studies reporting potentially modifiable risk factors for incident dementia after MCI. Two authors independently evaluated study quality using a checklist. Meta-analyses were conducted of three or more studies.
RESULTS
There were 76 eligible articles. Diabetes and prediabetes increased risk of conversion from amnestic MCI to Alzheimer's dementia; risk in treated versus untreated diabetes was lower in one study. Diabetes was also associated with increased risk of conversion from any-type or nonamnestic MCI to all-cause dementia. Metabolic syndrome and prediabetes predicted all-cause dementia in people with amnestic and any-type MCI, respectively. Mediterranean diet decreased the risk of conversion to Alzheimer's dementia. The presence of neuropsychiatric symptoms or lower serum folate levels predicted conversion from any-type MCI to all-cause dementia, but less formal education did not. Depressive symptoms predicted conversion from any-type MCI to all-cause dementia in epidemiological but not clinical studies.
CONCLUSIONS
Diabetes increased the risk of conversion to dementia. Other prognostic factors that are potentially manageable are prediabetes and the metabolic syndrome, neuropsychiatric symptoms, and low dietary folate. Dietary interventions and interventions to reduce neuropsychiatric symptoms, including depression, that increase risk of conversion to dementia may decrease new incidence of dementia.
Topics: Alzheimer Disease; Cognitive Dysfunction; Dementia; Depression; Diabetes Mellitus; Diet, Mediterranean; Disease Progression; Educational Status; Folic Acid; Humans; Longitudinal Studies; Metabolic Syndrome; Prediabetic State; Protective Factors; Risk Factors
PubMed: 25698435
DOI: 10.1176/appi.ajp.2014.14070878 -
JAMA Network Open Jan 2024The NAPOLI 3 trial showed the superiority of fluorouracil, leucovorin, liposomal irinotecan, and oxaliplatin (NALIRIFOX) over the combination of gemcitabine and... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
The NAPOLI 3 trial showed the superiority of fluorouracil, leucovorin, liposomal irinotecan, and oxaliplatin (NALIRIFOX) over the combination of gemcitabine and nab-paclitaxel (GEM-NABP) as first-line treatment of metastatic pancreatic ductal adenocarcinoma (PDAC). Analyses comparing NALIRIFOX and GEM-NABP with fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) have not yet been reported.
OBJECTIVE
To derive survival, response, and toxic effects data from phase 3 clinical trials and compare NALIRIFOX, FOLFIRINOX, and GEM-NABP.
DATA SOURCES
After a systematic search of PubMed, Scopus, Embase, and American Society of Clinical Oncology and European Society for Medical Oncology meetings' libraries, Kaplan-Meier curves were extracted from phase 3 clinical trials conducted from January 1, 2011, until September 12, 2023.
STUDY SELECTION
Phase 3 clinical trials that tested NALIRIFOX, FOLFIRINOX, or GEM-NABP as first-line treatment of metastatic PDAC and reported overall survival (OS) and progression-free survival (PFS) curves were selected. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses of Individual Participant Data reporting guidelines.
DATA EXTRACTION AND SYNTHESIS
Individual patient OS and PFS data were extracted from Kaplan-Meier plots of original trials via a graphic reconstructive algorithm. Overall response rates (ORRs) and grade 3 or higher toxic effects rates were also collected. A pooled analysis was conducted, and results were validated via a network meta-analysis.
MAIN OUTCOMES AND MEASURES
The primary end point was OS. Secondary outcomes included PFS, ORR, and toxic effects rates.
RESULTS
A total of 7 trials with data on 2581 patients were analyzed, including 383 patients treated with NALIRIFOX, 433 patients treated with FOLFIRINOX, and 1756 patients treated with GEM-NABP. Median PFS was longer in patients treated with NALIRIFOX (7.4 [95% CI, 6.1-7.7] months) or FOLFIRINOX (7.3 [95% CI, 6.5-7.9] months; [HR], 1.21 [95% CI, 0.86-1.70]; P = .28) compared with patients treated with GEM-NABP (5.7 [95% CI, 5.6-6.1] months; HR vs NALIRIFOX, 1.45 [95% CI, 1.22-1.73]; P < .001). Similarly, GEM-NABP was associated with poorer OS (10.4 [95% CI, 9.8-10.8]; months) compared with NALIRIFOX (HR, 1.18 [95% CI, 1.00-1.39]; P = .05], while no difference was observed between FOLFIRINOX (11.7 [95% CI, 10.4-13.0] months) and NALIRIFOX (11.1 [95% CI, 10.1-12.3] months; HR, 1.06 [95% CI, 0.81-1.39]; P = .65). There were no statistically significant differences in ORR among NALIRIFOX (41.8%), FOLFIRINOX (31.6%), and GEM-NABP (35.0%). NALIRIFOX was associated with lower incidence of grade 3 or higher hematological toxic effects (eg, platelet count decreased 1.6% vs 11.8% with FOLFIRINOX and 10.8% with GEM-NABP), but higher rates of severe diarrhea compared with GEM-NABP (20.3% vs 15.7%).
CONCLUSIONS AND RELEVANCE
In this systematic review and meta-analysis, NALIRIFOX and FOLFIRINOX were associated with similar PFS and OS as first-line treatment of advanced PDAC, although NALIRIFOX was associated with a different toxicity profile. Careful patient selection, financial toxic effects consideration, and direct comparison between FOLFIRINOX and NALIRIFOX are warranted.
Topics: Humans; Pancreatic Neoplasms; Irinotecan; Antineoplastic Combined Chemotherapy Protocols; Leucovorin; Oxaliplatin; Gemcitabine; Fluorouracil; Adenocarcinoma
PubMed: 38190183
DOI: 10.1001/jamanetworkopen.2023.50756 -
Nutrients Jan 2020Micronutrient deficiencies continue to be widespread among children under-five in low- and middle-income countries (LMICs), despite the fact that several effective... (Meta-Analysis)
Meta-Analysis
Micronutrient Supplementation and Fortification Interventions on Health and Development Outcomes among Children Under-Five in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis.
Micronutrient deficiencies continue to be widespread among children under-five in low- and middle-income countries (LMICs), despite the fact that several effective strategies now exist to prevent them. This kind of malnutrition can have several immediate and long-term consequences, including stunted growth, a higher risk of acquiring infections, and poor development outcomes, all of which may lead to a child not achieving his or her full potential. This review systematically synthesizes the available evidence on the strategies used to prevent micronutrient malnutrition among children under-five in LMICs, including single and multiple micronutrient (MMN) supplementation, lipid-based nutrient supplementation (LNS), targeted and large-scale fortification, and point-of-use-fortification with micronutrient powders (MNPs). We searched relevant databases and grey literature, retrieving 35,924 papers. After application of eligibility criteria, we included 197 unique studies. Of note, we examined the efficacy and effectiveness of interventions. We found that certain outcomes, such as anemia, responded to several intervention types. The risk of anemia was reduced with iron alone, iron-folic acid, MMN supplementation, MNPs, targeted fortification, and large-scale fortification. Stunting and underweight, however, were improved only among children who were provided with LNS, though MMN supplementation also slightly increased length-for-age z-scores. Vitamin A supplementation likely reduced all-cause mortality, while zinc supplementation decreased the incidence of diarrhea. Importantly, many effects of LNS and MNPs held when pooling data from effectiveness studies. Taken together, this evidence further supports the importance of these strategies for reducing the burden of micronutrient malnutrition in children. Population and context should be considered when selecting one or more appropriate interventions for programming.
Topics: Anemia, Iron-Deficiency; Child Nutrition Disorders; Child, Preschool; Developing Countries; Dietary Supplements; Female; Folic Acid; Food, Fortified; Growth Disorders; Humans; Income; Iron; Iron Deficiencies; Male; Micronutrients; Thinness; Trace Elements
PubMed: 31973225
DOI: 10.3390/nu12020289