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BMC Complementary Medicine and Therapies Jun 2021Elevated lipid profiles and impaired glucose homeostasis are risk factors for several cardiovascular diseases (CVDs), which, subsequently, represent a leading cause of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Elevated lipid profiles and impaired glucose homeostasis are risk factors for several cardiovascular diseases (CVDs), which, subsequently, represent a leading cause of early mortality, worldwide. The aim of the current study was to conduct a systematic review and meta-analysis of the effect of apple cider vinegar (ACV) on lipid profiles and glycemic parameters in adults.
METHODS
A systematic search was conducted in electronic databases, including Medline, Scopus, Cochrane Library, and Web of Knowledge, from database inception to January 2020. All clinical trials which investigated the effect of ACV on lipid profiles and glycemic indicators were included. Studies were excluded if ACV was used in combination with other interventions or when the duration of intervention was < 2 weeks. To account for between-study heterogeneity, we performed meta-analysis using a random-effects model.
RESULTS
Overall, nine studies, including 10 study arms, were included in this meta-analysis. We found that ACV consumption significantly decreased serum total cholesterol (- 6.06 mg/dL; 95% CI: - 10.95, - 1.17; I: 39%), fasting plasma glucose (- 7.97 mg/dL; 95% CI: - 13.74, - 2.21; I: 75%), and HbA1C concentrations (- 0.50; 95% CI: - 0.90, - 0.09; I: 91%). No significant effect of ACV consumption was found on serum LDL-C, HDL-C, fasting insulin concentrations, or HOMA-IR. The stratified analysis revealed a significant reduction of serum TC and TG in a subgroup of patients with type 2 diabetes, those who took ≤15 mL/day of ACV, and those who consumed ACV for > 8-weeks, respectively. Furthermore, ACV consumption significantly decreased FPG levels in a subgroup of studies that administered ACV for > 8-weeks. Further, ACV intake appeared to elicit an increase in FPG and HDL-C concentrations in apparently healthy participants.
CONCLUSION
We found a significant favorable effect of ACV consumption on FPG and blood lipid levels.
Topics: Acetic Acid; Blood Glucose; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Insulin; Malus; Randomized Controlled Trials as Topic
PubMed: 34187442
DOI: 10.1186/s12906-021-03351-w -
The Cochrane Database of Systematic... Dec 2021The optimal haemoglobin threshold for use of red blood cell (RBC) transfusions in anaemic patients remains an active field of research. Blood is a scarce resource, and... (Review)
Review
BACKGROUND
The optimal haemoglobin threshold for use of red blood cell (RBC) transfusions in anaemic patients remains an active field of research. Blood is a scarce resource, and in some countries, transfusions are less safe than in others because of inadequate testing for viral pathogens. If a liberal transfusion policy does not improve clinical outcomes, or if it is equivalent, then adopting a more restrictive approach could be recognised as the standard of care. OBJECTIVES: The aim of this review update was to compare 30-day mortality and other clinical outcomes for participants randomised to restrictive versus liberal red blood cell (RBC) transfusion thresholds (triggers) for all clinical conditions. The restrictive transfusion threshold uses a lower haemoglobin concentration as a threshold for transfusion (most commonly, 7.0 g/dL to 8.0 g/dL), and the liberal transfusion threshold uses a higher haemoglobin concentration as a threshold for transfusion (most commonly, 9.0 g/dL to 10.0 g/dL).
SEARCH METHODS
We identified trials through updated searches: CENTRAL (2020, Issue 11), MEDLINE (1946 to November 2020), Embase (1974 to November 2020), Transfusion Evidence Library (1950 to November 2020), Web of Science Conference Proceedings Citation Index (1990 to November 2020), and trial registries (November 2020). We checked the reference lists of other published reviews and relevant papers to identify additional trials. We were aware of one trial identified in earlier searching that was in the process of being published (in February 2021), and we were able to include it before this review was finalised.
SELECTION CRITERIA
We included randomised trials of surgical or medical participants that recruited adults or children, or both. We excluded studies that focused on neonates. Eligible trials assigned intervention groups on the basis of different transfusion schedules or thresholds or 'triggers'. These thresholds would be defined by a haemoglobin (Hb) or haematocrit (Hct) concentration below which an RBC transfusion would be administered; the haemoglobin concentration remains the most commonly applied marker of the need for RBC transfusion in clinical practice. We included trials in which investigators had allocated participants to higher thresholds or more liberal transfusion strategies compared to more restrictive ones, which might include no transfusion. As in previous versions of this review, we did not exclude unregistered trials published after 2010 (as per the policy of the Cochrane Injuries Group, 2015), however, we did conduct analyses to consider the differential impact of results of trials for which prospective registration could not be confirmed. DATA COLLECTION AND ANALYSIS: We identified trials for inclusion and extracted data using Cochrane methods. We pooled risk ratios of clinical outcomes across trials using a random-effects model. Two review authors independently extracted data and assessed risk of bias. We conducted predefined analyses by clinical subgroups. We defined participants randomly allocated to the lower transfusion threshold as being in the 'restrictive transfusion' group and those randomly allocated to the higher transfusion threshold as being in the 'liberal transfusion' group.
MAIN RESULTS
A total of 48 trials, involving data from 21,433 participants (at baseline), across a range of clinical contexts (e.g. orthopaedic, cardiac, or vascular surgery; critical care; acute blood loss (including gastrointestinal bleeding); acute coronary syndrome; cancer; leukaemia; haematological malignancies), met the eligibility criteria. The haemoglobin concentration used to define the restrictive transfusion group in most trials (36) was between 7.0 g/dL and 8.0 g/dL. Most trials included only adults; three trials focused on children. The included studies were generally at low risk of bias for key domains including allocation concealment and incomplete outcome data. Restrictive transfusion strategies reduced the risk of receiving at least one RBC transfusion by 41% across a broad range of clinical contexts (risk ratio (RR) 0.59, 95% confidence interval (CI) 0.53 to 0.66; 42 studies, 20,057 participants; high-quality evidence), with a large amount of heterogeneity between trials (I² = 96%). Overall, restrictive transfusion strategies did not increase or decrease the risk of 30-day mortality compared with liberal transfusion strategies (RR 0.99, 95% CI 0.86 to 1.15; 31 studies, 16,729 participants; I² = 30%; moderate-quality evidence) or any of the other outcomes assessed (i.e. cardiac events (low-quality evidence), myocardial infarction, stroke, thromboembolism (all high-quality evidence)). High-quality evidence shows that the liberal transfusion threshold did not affect the risk of infection (pneumonia, wound infection, or bacteraemia). Transfusion-specific reactions are uncommon and were inconsistently reported within trials. We noted less certainty in the strength of evidence to support the safety of restrictive transfusion thresholds for the following predefined clinical subgroups: myocardial infarction, vascular surgery, haematological malignancies, and chronic bone-marrow disorders.
AUTHORS' CONCLUSIONS
Transfusion at a restrictive haemoglobin concentration decreased the proportion of people exposed to RBC transfusion by 41% across a broad range of clinical contexts. Across all trials, no evidence suggests that a restrictive transfusion strategy impacted 30-day mortality, mortality at other time points, or morbidity (i.e. cardiac events, myocardial infarction, stroke, pneumonia, thromboembolism, infection) compared with a liberal transfusion strategy. Despite including 17 more randomised trials (and 8846 participants), data remain insufficient to inform the safety of transfusion policies in important and selected clinical contexts, such as myocardial infarction, chronic cardiovascular disease, neurological injury or traumatic brain injury, stroke, thrombocytopenia, and cancer or haematological malignancies, including chronic bone marrow failure. Further work is needed to improve our understanding of outcomes other than mortality. Most trials compared only two separate thresholds for haemoglobin concentration, which may not identify the actual optimal threshold for transfusion in a particular patient. Haemoglobin concentration may not be the most informative marker of the need for transfusion in individual patients with different degrees of physiological adaptation to anaemia. Notwithstanding these issues, overall findings provide good evidence that transfusions with allogeneic RBCs can be avoided in most patients with haemoglobin thresholds between the range of 7.0 g/dL and 8.0 g/dL. Some patient subgroups might benefit from RBCs to maintain higher haemoglobin concentrations; research efforts should focus on these clinical contexts.
Topics: Anemia; Erythrocyte Transfusion; Hematocrit; Hemoglobins; Humans; Prospective Studies; Randomized Controlled Trials as Topic
PubMed: 34932836
DOI: 10.1002/14651858.CD002042.pub5 -
Current Cardiology Reviews 2021Globally, dyslipidemia has been shown to be an independent predictor of many cardiovascular and cerebrovascular events, which led to recent advocacy towards dyslipidemia...
BACKGROUND
Globally, dyslipidemia has been shown to be an independent predictor of many cardiovascular and cerebrovascular events, which led to recent advocacy towards dyslipidemia prevention and control as a key risk factor and its prognostic significance to reduce the burden of stroke and myocardial infarction (MI).
AIMS
This study aimed to evaluate hyperlipidemia as a risk factor connected with stroke and CVD. Moreover, having identified this risk factor, the study evaluates how hyperlipidemia has been examined earlier and what can be done in the future.
METHODS
All prospective studies concerning hyperlipidemia as risk factors for stroke and CVD were identified by a search of PubMed/MEDLINE and EMBASE databases with keywords hyperlipidemia, risk factors, stroke, and cardiovascular disease.
RESULTS
The constant positive association between the incidence of coronary heart disease and cholesterol concentration of LDL is apparent in observational studies in different populations. Thus, the reduction of LDL cholesterol in those populations, particularly with regard to initial cholesterol concentrations, can reduce the risk of vascular diseases. However, the impact of using lipid-lowering drugs, such as statins, has been demonstrated in several studies as an important factor in decreasing the mortality and morbidity rates of patients with stroke and CVD.
CONCLUSION
After reviewing all the research mentioned in this review, most studies confirmed that hyperlipidemia is a risk factor for stroke and correlated in patients with CVD.
Topics: Cardiovascular Diseases; Cholesterol, LDL; Humans; Hyperlipidemias; Prospective Studies; Stroke
PubMed: 33305711
DOI: 10.2174/1573403X16999201210200342 -
The Cochrane Database of Systematic... Sep 2021Anaemia is a prevalent health problem worldwide. Some types are preventable or controllable with iron supplementation (pills or drops), fortification (sprinkles or... (Review)
Review
BACKGROUND
Anaemia is a prevalent health problem worldwide. Some types are preventable or controllable with iron supplementation (pills or drops), fortification (sprinkles or powders containing iron added to food) or improvements to dietary diversity and quality (e.g. education or counselling).
OBJECTIVES
To summarise the evidence from systematic reviews regarding the benefits or harms of nutrition-specific interventions for preventing and controlling anaemia in anaemic or non-anaemic, apparently healthy populations throughout the life cycle.
METHODS
In August 2020, we searched MEDLINE, Embase and 10 other databases for systematic reviews of randomised controlled trials (RCTs) in anaemic or non-anaemic, apparently healthy populations. We followed standard Cochrane methodology, extracting GRADE ratings where provided. The primary outcomes were haemoglobin (Hb) concentration, anaemia, and iron deficiency anaemia (IDA); secondary outcomes were iron deficiency (ID), severe anaemia and adverse effects (e.g. diarrhoea, vomiting).
MAIN RESULTS
We included 75 systematic reviews, 33 of which provided GRADE assessments; these varied between high and very low. Infants (6 to 23 months; 13 reviews) Iron supplementation increased Hb levels and reduced the risk of anaemia and IDA in two reviews. Iron fortification of milk or cereals, multiple-micronutrient powder (MMNP), home fortification of complementary foods, and supplementary feeding increased Hb levels and reduced the risk of anaemia in six reviews. In one review, lipid-based nutrient supplementation (LNS) reduced the risk of anaemia. In another, caterpillar cereal increased Hb levels and IDA prevalence. Food-based strategies (red meat and fortified cow's milk, beef) showed no evidence of a difference (1 review). Preschool and school-aged children (2 to 10 years; 8 reviews) Daily or intermittent iron supplementation increased Hb levels and reduced the risk of anaemia and ID in two reviews. One review found no evidence of difference in Hb levels, but an increased risk of anaemia and ID for the intermittent regime. All suggested that zinc plus iron supplementation versus zinc alone, multiple-micronutrient (MMN)-fortified beverage versus control, and point-of-use fortification of food with iron-containing micronutrient powder (MNP) versus placebo or no intervention may increase Hb levels and reduce the risk of anaemia and ID. Fortified dairy products and cereal food showed no evidence of a difference on the incidence of anaemia (1 review). Adolescent children (11 to 18 years; 4 reviews) Compared with no supplementation or placebo, five types of iron supplementation may increase Hb levels and reduce the risk of anaemia (3 reviews). One review on prevention found no evidence of a difference in anaemia incidence on iron supplementation with or without folic acid, but Hb levels increased. Another suggested that nutritional supplementation and counselling reduced IDA. One review comparing MMN fortification with no fortification observed no evidence of a difference in Hb levels. Non-pregnant women of reproductive age (19 to 49 years; 5 reviews) Two reviews suggested that iron therapy (oral, intravenous (IV), intramuscular (IM)) increased Hb levels; one showed that iron folic acid supplementation reduced anaemia incidence; and another that daily iron supplementation with or without folic acid or vitamin C increased Hb levels and reduced the risk of anaemia and ID. No review reported interventions related to fortification or dietary diversity and quality. Pregnant women of reproductive age (15 to 49 years; 23 reviews) One review apiece suggested that: daily iron supplementation with or without folic acid increased Hb levels in the third trimester or at delivery and in the postpartum period, and reduced the risk of anaemia, IDA and ID in the third trimester or at delivery; intermittent iron supplementation had no effect on Hb levels and IDA, but increased the risk of anaemia at or near term and ID, and reduced the risk of side effects; vitamin A supplementation alone versus placebo, no intervention or other micronutrient might increase maternal Hb levels and reduce the risk of maternal anaemia; MMN with iron and folic acid versus placebo reduced the risk of anaemia; supplementation with oral bovine lactoferrin versus oral ferrous iron preparations increased Hb levels and reduced gastrointestinal side effects; MNP for point-of-use fortification of food versus iron and folic acid supplementation might decrease Hb levels at 32 weeks' gestation and increase the risk of anaemia; and LNS versus iron or folic acid and MMN increased the risk of anaemia. Mixed population (all ages; 22 reviews) Iron supplementation versus placebo or control increased Hb levels in healthy children, adults, and elderly people (4 reviews). Hb levels appeared to increase and risk of anaemia and ID decrease in two reviews investigating MMN fortification versus placebo or no treatment, iron fortified flour versus control, double fortified salt versus iodine only fortified salt, and rice fortification with iron alone or in combination with other micronutrients versus unfortified rice or no intervention. Each review suggested that fortified versus non-fortified condiments or noodles, fortified (sodium iron ethylenediaminetetraacetate; NaFeEDTA) versus non-fortified soy sauce, and double-fortified salt versus control salt may increase Hb concentration and reduce the risk of anaemia. One review indicated that Hb levels increased for children who were anaemic or had IDA and received iron supplementation, and decreased for those who received dietary interventions. Another assessed the effects of foods prepared in iron pots, and found higher Hb levels in children with low-risk malaria status in two trials, but no difference when comparing food prepared in non-cast iron pots in a high-risk malaria endemicity mixed population. There was no evidence of a difference for adverse effects. Anaemia and malaria prevalence were rarely reported. No review focused on women aged 50 to 65 years plus or men (19 to 65 years plus).
AUTHORS' CONCLUSIONS
Compared to no treatment, daily iron supplementation may increase Hb levels and reduce the risk of anaemia and IDA in infants, preschool and school-aged children and pregnant and non-pregnant women. Iron fortification of foods in infants and use of iron pots with children may have prophylactic benefits for malaria endemicity low-risk populations. In any age group, only a limited number of reviews assessed interventions to improve dietary diversity and quality. Future trials should assess the effects of these types of interventions, and consider the requirements of different populations.
Topics: Adolescent; Adult; Aged; Anemia; Anemia, Iron-Deficiency; Animals; Child; Dietary Supplements; Female; Food, Fortified; Humans; Iron; Life Cycle Stages; Male; Micronutrients; Middle Aged; Pregnancy; Systematic Reviews as Topic; Young Adult
PubMed: 34564844
DOI: 10.1002/14651858.CD013092.pub2 -
Pharmacotherapy Apr 2022Rifamycins (rifampin, rifabutin, and rifapentine) play an essential role in the treatment of mycobacterial and some nonmycobacterial infections. They also induce the... (Review)
Review
Rifamycins (rifampin, rifabutin, and rifapentine) play an essential role in the treatment of mycobacterial and some nonmycobacterial infections. They also induce the activity of various drug transporting and metabolizing enzymes, which can impact the concentrations and efficacy of substrates. Many anticoagulant and antiplatelet (AC/AP) agents are substrates of these enzymes and have narrow therapeutic indices, leading to risks of thrombosis or bleeding when coadministered with rifamycins. The objective of this systematic review was to evaluate the effects on AC/AP pharmacokinetics, laboratory markers, and clinical safety and efficacy of combined use with rifamycins. A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidance was performed. The PubMed, Embase, and Web of Science databases were queried for English-language reports on combination use of rifamycins and AC/AP agents from database inception through August 2021. The 29 studies identified examined warfarin (n = 17), direct oral anticoagulants (DOACs) (n = 8), and antiplatelet agents (n = 4) combined with rifampin (n = 28) or rifabutin (n = 1). Eleven studies were case reports or small case series; 14 reported on pharmacokinetic or laboratory markers in healthy volunteers. Rifampin-warfarin combinations led to reductions in warfarin area under the curve (AUC) of 15%-74%, with variability by warfarin isomer and study. Warfarin dose increases of up to 3-5 times prerifampin doses were required to maintain coagulation parameters in the therapeutic range. DOAC AUCs were decreased by 20%-67%, with variability by individual agent and with rifampin versus rifabutin. The active metabolite of clopidogrel increased substantially with rifampin coadministration, whereas prasugrel was largely unaffected and ticagrelor saw decreases. Our review suggests most combinations of AC/AP agents and rifampin are problematic. Further studies are required to determine whether rifabutin or rifapentine could be safe alternatives for coadministration with AC/AP drugs.
Topics: Anticoagulants; Drug Interactions; Humans; Platelet Aggregation Inhibitors; Rifabutin; Rifampin; Rifamycins; Warfarin
PubMed: 35152432
DOI: 10.1002/phar.2672 -
Effects of dietary supplements on athletic performance in elite soccer players: a systematic review.Journal of the International Society of... Dec 2023Dietary supplements are widely used among athletes, and soccer players are no exception. Nevertheless, evidence supporting the use of dietary supplements aiming to... (Review)
Review
Dietary supplements are widely used among athletes, and soccer players are no exception. Nevertheless, evidence supporting the use of dietary supplements aiming to enhance performance in soccer is somewhat contradictory, scarce, or even nonexistent. Thus, the present study aimed to systematically review and synthesize the effects of dietary supplements on athletic performance (e.g. distance covered, sprinting, jump performance) in elite soccer players. Studies enrolling highly trained, elite, and world-class soccer players using dietary supplements were searched in MEDLINE/PubMed, Web of Science, Scopus, and EBSCO databases in June 2022. In total, 1043 studies were identified, and 18 met the eligibility criteria. The studies evaluated the impacts on athletic performance of several dietary supplements, including caffeine, creatine, protein, beverages with carbohydrates and electrolytes, tart cherry juice, nitrate-rich beetroot juice, sodium bicarbonate with minerals, yohimbine, and a proprietary nutraceutical blend. Caffeine supplementation in doses between 3 and 6 mg/kg of body mass may improve jump height and sprint ability, particularly in female players, but individual response to caffeine must be considered. Creatine may improve sprint, agility, and in female players, jump performance. Protein supplementation can improve sprint and jump performance between matches, especially if protein ingested from food is not up to recommendations. Beverages containing carbohydrates and electrolytes can be used as part of the strategies to achieve carbohydrate intake during training and match-days but used alone do not benefit athletic performance. Tart cherry juice might be useful for maintaining athletic performance after matches that produce higher force loss and exercise-induced muscle damage, although polyphenols from the diet might attenuate the effects of tart cherry supplementation. Nitrate-rich beetroot concentrate can attenuate performance decrease in the days following matches. Further investigation with sodium bicarbonate alone is necessary, as supplementation protocols with elite players included other substances. Finally, the available data does not support yohimbine supplementation or the use of Resurgex Plus® to improve athletic performance in elite soccer players. Still, more well-designed research with elite soccer players is needed to improve support and advice regarding the use of dietary supplements for athletic performance enhancement.
Topics: Humans; Female; Soccer; Caffeine; Sodium Bicarbonate; Creatine; Nitrates; Athletic Performance; Dietary Supplements; Electrolytes; Carbohydrates
PubMed: 37462346
DOI: 10.1080/15502783.2023.2236060 -
Clinical Pharmacokinetics Aug 2022Metoprolol is recommended for therapeutic use in multiple cardiovascular conditions, thyroid crisis, and circumscribed choroidal hemangioma. A detailed systematic review...
BACKGROUND
Metoprolol is recommended for therapeutic use in multiple cardiovascular conditions, thyroid crisis, and circumscribed choroidal hemangioma. A detailed systematic review on the metoprolol literature would be beneficial to assess all pharmacokinetic parameters in humans and their respective effects on patients with hepatic, renal, and cardiovascular diseases. This review combines all the pharmacokinetic data on metoprolol from various accessible studies, which may assist in clinical decision making.
METHODOLOGY
The Google Scholar and PubMed databases were searched to screen articles associated with the clinical pharmacokinetics of metoprolol. The comprehensive literature search retrieved 41 articles including data on plasma concentration-time profiles after intravenous and oral (immediate-release, controlled-release, slow-release, or extended-release) routes of administration, and at least one pharmacokinetic parameter was reported in all studies included.
RESULTS
Out of 41 retrieved articles, six were after intravenous and 12 were after oral administration in healthy individuals. The oral studies depict a dose-dependent increase in maximum plasma concentration (C), time to reach maximum plasma concentration (T), and area under the concentration-time curve (AUC). Two studies were conducted in R- and S-enantiomers, in which one study reported the gender differences, depicting greater C and AUC among women, whereas in another study S-metoprolol was found to have higher values of C, T, and AUC in comparison with R-metoprolol. Results in different diseases depicted that after IV administration of 20 mg, patients with renal impairment showed an increase in clearance (CL) (60 L/h vs 48 L/h) compared with healthy subjects, whereas a decrease in CL (36.6 ± 7.8 L/h vs 48 ± 6.6 L/h) was seen in patients with hepatic cirrhosis at a similar dose. In comparison with a single oral dose following administration of 15 mg IV in three divided doses, patients having an acute myocardial infarction (AMI) showed an increase in C (823 nmol/L vs 248 nmol/L) at a steady state. Twenty different studies have reported significant changes in CL, C and AUC of metoprolol when it is co-administered with other drugs. One study has reported a drug-food interaction for metoprolol but no significant changes were seen in the C and AUC.
CONCLUSION
This review summarizes all the pharmacokinetic parameters of metoprolol after pooling up-to-date data from all the studies available. The summarized pharmacokinetic data presented in this review can assist in developing and evaluating pharmacokinetic models of metoprolol. Moreover, this data can provide practitioners with an insight into dosage adjustments among the diseased populations and can assist in preventing potential adverse drug reactions. This review can also help avoid side effects and drug-drug interactions.
Topics: Administration, Oral; Area Under Curve; Female; Food-Drug Interactions; Humans; Liver; Metoprolol
PubMed: 35764772
DOI: 10.1007/s40262-022-01145-y -
Nutrients Dec 2020The association between vitamin D status and autism spectrum disorder (ASD) is well-investigated but remains to be elucidated. We quantitatively combined relevant... (Meta-Analysis)
Meta-Analysis Review
The association between vitamin D status and autism spectrum disorder (ASD) is well-investigated but remains to be elucidated. We quantitatively combined relevant studies to estimate whether vitamin D status was related to ASD in this work. PubMed, EMBASE, Web of Science, and the Cochrane Library were searched to include eligible studies. A random-effects model was applied to pool overall estimates of vitamin D concentration or odds ratio (OR) for ASD. In total, 34 publications involving 20,580 participants were identified in this present study. Meta-analysis of 24 case-control studies demonstrated that children and adolescents with ASD had significantly lower vitamin D concentration than that of the control group (mean difference (MD): -7.46 ng/mL, 95% confidence interval (CI): -10.26; -4.66 ng/mL, < 0.0001, I = 98%). Quantitative integration of 10 case-control studies reporting OR revealed that lower vitamin D was associated with higher risk of ASD (OR: 5.23, 95% CI: 3.13; 8.73, < 0.0001, I = 78.2%). Analysis of 15 case-control studies barring data from previous meta-analysis reached a similar result with that of the meta-analysis of 24 case-control studies (MD: -6.2, 95% CI: -9.62; -2.78, = 0.0004, I = 96.8%), which confirmed the association. Furthermore, meta-analysis of maternal and neonatal vitamin D showed a trend of decreased early-life vitamin D concentration in the ASD group (MD: -3.15, 95% CI: -6.57; 0.26, = 0.07, I = 99%). Meta-analysis of prospective studies suggested that children with reduced maternal or neonatal vitamin D had 54% higher likelihood of developing ASD (OR: 1.54, 95% CI: 1.12; 2.10, = 0.0071, I = 81.2%). These analyses indicated that vitamin D status was related to the risk of ASD. The detection and appropriate intervention of vitamin D deficiency in ASD patients and pregnant and lactating women have clinical and public significance.
Topics: Autism Spectrum Disorder; Databases, Factual; Female; Humans; Pregnancy; Pregnant Women; Vitamin D; Vitamin D Deficiency
PubMed: 33383952
DOI: 10.3390/nu13010086 -
The Cochrane Database of Systematic... Dec 2021Varicose veins are enlarged and tortuous veins, affecting up to one-third of the world's population. They can be a cause of chronic venous insufficiency, which is... (Review)
Review
BACKGROUND
Varicose veins are enlarged and tortuous veins, affecting up to one-third of the world's population. They can be a cause of chronic venous insufficiency, which is characterised by oedema, pigmentation, eczema, lipodermatosclerosis, atrophie blanche, and healed or active venous ulcers. Injection sclerotherapy (liquid or foam) is widely used for treatment of varicose veins aiming to transform the varicose veins into a fibrous cord. However, there is limited evidence regarding its effectiveness and safety, especially in patients with more severe disease. This is the second update of the review first published in 2002.
OBJECTIVES
To assess the effectiveness and safety of injection sclerotherapy for the treatment of varicose veins.
SEARCH METHODS
For this update, the Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, AMED, CINAHL, and LILACS databases, and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registries, on 20 July 2021.
SELECTION CRITERIA
We included all randomised controlled trials (RCTs) (including cluster-randomised trials and first phase cross-over studies) that used injection sclerotherapy for the treatment of varicose veins.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed, selected and extracted data. Disagreements were cross-checked by a third review author. We used Cochrane's Risk of bias tool to assess the risk of bias. The outcomes of interest were cosmetic appearance, complications, residual varicose veins, quality of life (QoL), persistence of symptoms, and recurrent varicose veins. We calculated risk ratios (RRs) or mean difference (MD) with 95% confidence intervals (CIs). We used the worst-case-scenario for dichotomous data imputation for intention-to-treat analyses. For continuous outcomes, we used the 'last-observation-carried-forward' for data imputation if there was balanced loss to follow-up. We assessed the certainty of the evidence using the GRADE approach.
MAIN RESULTS
We included 23 new RCTs for this update, bringing the total to 28 studies involving 4278 participants. The studies differed in their design, and in which sclerotherapy method, agent or concentration was used. None of the included RCTs compared sclerotherapy to no intervention or to any pharmacological therapy. The certainty of the evidence was downgraded for risk of bias, low number of studies providing information for each outcome, low number of participants, clinical differences between the study participants, and wide CIs. Sclerotherapy versus placebo Foam sclerotherapy may improve cosmetic appearance as measured by IPR-V (independent photography review - visible varicose veins scores) compared to placebo (polidocanol 1%: mean difference (MD) -0.76, 95% CI -0.91 to -0.60; 2 studies, 223 participants; very low-certainty evidence); however, deep vein thrombosis (DVT) rates may be slightly increased in this intervention group (RR 5.10, 95% CI 1.30 to 20.01; 3 studies, 302 participants; very low-certainty evidence). Residual varicose vein rates may be decreased following polidocanol 1% compared to placebo (RR 0.19, 95% CI 0.13 to 0.29; 2 studies, 225 participants; very low-certainty evidence). Following polidocanol 1% use, there may be a possible improvement in QoL as assessed using the VEINES-QOL/Sym questionnaire (MD 12.41, 95% CI 9.56 to 15.26; 3 studies, 299 participants; very low-certainty evidence), and possible improvement in varicose vein symptoms as assessed using the Venous Clinical Severity Score (VCSS) (MD -3.25, 95% CI -3.90 to -2.60; 2 studies, 223 participants; low-certainty evidence). Recurrent varicose veins were not reported for this comparison. Foam sclerotherapy versus foam sclerotherapy with different concentrations Three individual RCTs reported no evidence of a difference in cosmetic appearance after comparing different concentrations of the intervention; data could not be pooled for two of the three studies (RR 1.11, 95% CI 0.84 to 1.47; 1 study, 80 participants; very low-certainty evidence). Similarly, there was no clear difference in rates of thromboembolic complications when comparing one foam concentration with another (RR 1.47, 95% CI 0.41 to 5.33; 3 studies, 371 participants; very low-certainty evidence). Three RCTs investigating higher concentrations of polidocanol foam indicated the rate of residual varicose veins may be slightly decreased in the polidocanol 3% foam group compared to 1% (RR 0.67, 95% CI 0.43 to 1.04; 3 studies, 371 participants; moderate-certainty evidence). No clear improvement in QoL was detected. Two RCTs reported improved VCSS scores with increasing concentrations of foam. Persistence of symptoms were not reported for this comparison. There was no clear difference in recurrent varicose vein rates (RR 0.91, 95% CI 0.62 to 1.32; 1 study, 148 participants; low-certainty evidence). Foam sclerotherapy versus liquid sclerotherapy One RCT reported on cosmetic appearance with no evidence of a difference between foam or liquid sclerotherapy (patient satisfaction scale MD 0.2, 95% CI -0.27 to 0.67; 1 study, 126 participants; very low-certainty evidence). None of the RCTs investigated thromboembolic complications, QoL or persistence of symptoms. Six studies individually showed there may be a benefit to polidocanol 3% foam over liquid sclerotherapy in reducing residual varicose vein rate; pooling data from two studies showed a RR of 0.51, with 95% CI 0.41 to 0.65; 203 participants; very low-certainty evidence. One study reported no clear difference in recurrent varicose vein rates when comparing sodium tetradecyl sulphate (STS) foam or liquid (RR 1.10, 95% CI 0.86 to 1.42; 1 study, 286 participants; very low-certainty evidence). Sclerotherapy versus sclerotherapy with different substances Four RCTs compared sclerotherapy versus sclerotherapy with any other substance. We were unable to combine the data due to heterogeneity or assess the certainty of the evidence due to insufficient data.
AUTHORS' CONCLUSIONS
There is a very low to low-certainty evidence that, compared to placebo, sclerotherapy is an effective and safe treatment for varicose veins concerning cosmetic appearance, residual varicose veins, QoL, and persistence of symptoms. Rates of DVT may be slightly increased and there were no data concerning recurrent varicose veins. There was limited or no evidence for one concentration of foam compared to another; foam compared to liquid sclerotherapy; foam compared to any other substance; or one technique compared to another. There is a need for high-quality trials using standardised sclerosant doses, with clearly defined core outcome sets, and measurement time points to increase the certainty of the evidence.
Topics: Humans; Sclerotherapy; Varicose Ulcer; Varicose Veins; Veins; Venous Insufficiency
PubMed: 34883526
DOI: 10.1002/14651858.CD001732.pub3 -
Human Reproduction Update Nov 2023Current knowledge about the consequences of PCOS during the late reproductive years and after menopause is limited. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Current knowledge about the consequences of PCOS during the late reproductive years and after menopause is limited.
OBJECTIVE AND RATIONALE
We performed a systematic review and meta-analysis of data on the pathophysiology, clinical manifestations, diagnosis, prognosis, and treatment of women ≥45 years of age-peri- or postmenopausal-with PCOS.
SEARCH METHODS
Studies published up to 15 April 2023, identified by Entrez-PubMed, EMBASE, and Scopus online facilities, were considered. We included cross-sectional or prospective studies that reported data from peri- or postmenopausal patients with PCOS and control women with a mean age ≥45 years. Three independent researchers performed data extraction. Meta-analyses of quantitative data used random-effects models because of the heterogeneity derived from differences in study design and criteria used to define PCOS, among other confounding factors. Sensitivity analyses restricted the meta-analyses to population-based studies, to studies including only patients diagnosed using the most widely accepted definitions of PCOS, only menopausal women or only women not submitted to ovarian surgery, and studies in which patients and controls presented with similar indexes of weight excess. Quality of evidence was assessed using the GRADE system.
OUTCOMES
The initial search identified 1400 articles, and another six were included from the reference lists of included articles; 476 duplicates were deleted. We excluded 868 articles for different reasons, leaving 37 valid studies for the qualitative synthesis, of which 28 studies-published in 41 articles-were considered for the quantitative synthesis and meta-analyses. Another nine studies were included only in the qualitative analyses. Compared with controls, peri- and postmenopausal patients with PCOS presented increased circulating total testosterone (standardized mean difference, SMD 0.78 (0.35, 1.22)), free androgen index (SMD 1.29 (0.89, 1.68)), and androstenedione (SMD 0.58 (0.23, 0.94)), whereas their sex hormone-binding globulin was reduced (SMD -0.60 (-0.76, -0.44)). Women with PCOS showed increased BMI (SMD 0.57 (0.32, 0.75)), waist circumference (SMD 0.64 (0.42, 0.86)), and waist-to-hip ratio (SMD 0.38 (0.14, 0.61)) together with increased homeostasis model assessment of insulin resistance (SMD 0.56 (0.27, 0.84)), fasting insulin (SMD 0.61 (0.38, 0.83)), fasting glucose (SMD 0.48 (0.29, 0.68)), and odds ratios (OR, 95% CI) for diabetes (OR 3.01 (1.91, 4.73)) compared to controls. Women with PCOS versus controls showed decreased HDL concentrations (SMD -0.32 (-0.46, -0.19)) and increased triglycerides (SMD 0.31 (0.16, 0.46)), even though total cholesterol and LDL concentrations, as well as the OR for dyslipidaemia, were similar to those of controls. The OR for having hypertension was increased in women with PCOS compared with controls (OR 1.79 (1.36, 2.36)). Albeit myocardial infarction (OR 2.51 (1.08, 5.81)) and stroke (OR 1.75 (1.03, 2.99)) were more prevalent in women with PCOS than controls, the ORs for cardiovascular disease as a whole, coronary artery disease as a whole, breast cancer and age at menopause, were similar in patients and controls. When restricting meta-analysis to studies in which women with PCOS and controls had a similar mean BMI, the only difference that retained statistical significance was a decrease in HDL-cholesterol concentration in the former and, in the two studies in which postmenopausal women with PCOS and controls had similar BMI, patients presented with increased serum androgen concentrations, suggesting that hyperandrogenism persists after menopause, regardless of obesity.
WIDER IMPLICATIONS
Hyperandrogenism appeared to persist during the late-reproductive years and after menopause in women with PCOS. Most cardiometabolic comorbidities were driven by the frequent coexistence of weight excess and PCOS, highlighting the importance of targeting obesity in this population. However, the significant heterogeneity among included studies, and the overall low quality of the evidence gathered here, precludes reaching definite conclusions on the issue. Hence, guidelines derived from adequately powered prospective studies are definitely needed for appropriate management of these women.
Topics: Humans; Female; Middle Aged; Androgens; Polycystic Ovary Syndrome; Hyperandrogenism; Cross-Sectional Studies; Prospective Studies; Obesity; Menopause; Cholesterol
PubMed: 37353908
DOI: 10.1093/humupd/dmad015