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The Journal of Dermatological Treatment Jun 2022Melasma is a common chronic refractory disorder of pigmentation affecting people with darker skin types. Overall prevalence varies between 8.8% and 40%, depending on the... (Review)
Review
Melasma is a common chronic refractory disorder of pigmentation affecting people with darker skin types. Overall prevalence varies between 8.8% and 40%, depending on the ethnicity of the population and the geographical area. Therapeutic management of melasma is challenging, with high recurrence rates which significant impacts on the quality of life. No single treatment is universally efficacious. Systemic treatments with tranexamic acid and polypodium leucotmatous had promising results, although the former was related to systemic side effects. Microneedling and peeling were also efficacious, although their superiority to topical hydroquinone, the gold standard in melasma treatment, remains to be established. Similarly, laser and light devices have been beneficial. However, recurrence rates remain high in all treatment groups. Combination therapies, either in double or triple combinations yielded the best results when compared to single terapies. Treatment choice should be made after Wood's lamp examination, as well as dermatoscopic evaluation, in order to select the best treatment option, targeted at each melasma subtype.
Topics: Administration, Cutaneous; Humans; Melanosis; Quality of Life; Tranexamic Acid; Treatment Outcome
PubMed: 33849384
DOI: 10.1080/09546634.2021.1914313 -
American Journal of Clinical Dermatology Apr 2020Melasma is an acquired, chronic pigmentary disorder predominantly affecting women. It may significantly affect quality of life and self-esteem due to its disfiguring...
BACKGROUND
Melasma is an acquired, chronic pigmentary disorder predominantly affecting women. It may significantly affect quality of life and self-esteem due to its disfiguring appearance. Multiple treatments for melasma are available, with mixed results.
OBJECTIVE
The aim of this article was to conduct an evidence-based review of all available interventions for melasma.
METHODS
A systematic literature search of the PubMed electronic database was performed using the keywords 'melasma' and/or 'chloasma' in the title, through October 2018. The search was then limited to 'randomized controlled trial' and 'controlled clinical trial' in English-language journals. The Cochrane database was also searched for systematic reviews.
RESULTS
The electronic search yielded a total of 212 citations. Overall, 113 studies met the inclusion criteria and were included in this review, with a total of 6897 participants. Interventions included topical agents, chemical peels, laser- and light-based devices, and oral agents. Triple combination cream (hydroquinone, tretinoin, and corticosteroid) remains the most effective treatment for melasma, as well as hydroquinone alone. Chemical peels and laser- and light-based devices have mixed results. Oral tranexamic acid is a promising new treatment for moderate and severe recurrent melasma. Adverse events from all treatments tend to be mild, and mainly consist of skin irritation, dryness, burning, erythema, and post-inflammatory hyperpigmentation.
CONCLUSIONS
Hydroquinone monotherapy and triple combination cream are the most effective and well-studied treatments for melasma, whereas chemical peels and laser- and light-based therapies are equal or inferior to topicals, but offer a higher risk of adverse effects. Oral tranexamic acid may be a safe, systemic adjunctive treatment for melasma, but more studies are needed to determine its long-term safety and efficacy. Limitations of the current evidence are heterogeneity of study design, small sample size, and lack of long-term follow-up, highlighting the need for larger, more rigorous studies in the treatment of this recalcitrant disorder.
Topics: Chemexfoliation; Humans; Laser Therapy; Melanosis; Retinoids; Skin Lightening Preparations; Tranexamic Acid
PubMed: 31802394
DOI: 10.1007/s40257-019-00488-w -
Critical Care Medicine Mar 2022Tranexamic acid is proposed as a treatment for gastrointestinal bleeding. The Haemorrhage Alleviation with Tranexamic Acid-Intestinal System trial evaluated extended-use... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Tranexamic acid is proposed as a treatment for gastrointestinal bleeding. The Haemorrhage Alleviation with Tranexamic Acid-Intestinal System trial evaluated extended-use (24 hr) high-dose tranexamic acid, prompting a reappraisal for tranexamic acid in gastrointestinal bleeding.
DATA SOURCES
We conducted a systematic review and meta-analysis of randomized controlled trials comparing tranexamic acid with usual care or placebo in adults with gastrointestinal bleeding. We searched MEDLINE, EMBASE, and CENTRAL (inception to September 2019).
DATA SELECTION
Two reviewers independently screened citations, extracted data, and assessed the risk of bias using the Cochrane risk of bias tool in duplicate. The main outcomes were mortality, bleeding, and adverse events.
DATA EXTRACTION
Studies were analyzed as high-dose IV tranexamic acid versus all other dosing strategies for tranexamic acid using fixed-effects models. We assessed certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach.
DATA SYNTHESIS
Five randomized controlled trials evaluated extended-use high-dose IV tranexamic acid, seven evaluating low-dose IV or enteral tranexamic acid. Extended-use high-dose IV tranexamic acid did not reduce mortality (relative risk, 0.98%; 95% CI, 0.88-1.09; I2 = 63%; high certainty) or bleeding (relative risk, 0.92; 95% CI, 0.82-1.04; p = 0.17 and absolute risk differences, -0.7%; 95% CI, -1.5 to 0.3; high certainty) but resulted in a small increase in deep venous thrombosis (relative risk, 2.01; 95% CI, 1.08-3.72; I2 = 0%), pulmonary embolism (relative risk, 1.78; 95% CI, 1.06-3.0; I2 = 0%), and seizure (relative risk, 1.73; 95% CI, 1.03-2.93) with high certainty. Low-dose IV/enteral tranexamic acid did not reduce mortality (relative risk, 0.62; 95% CI, 0.36-1.09; I2 = 0%) but did reduce risk of rebleeding (relative risk, 0.5; 95% CI, 0.33-0.75; I2 = 9%) and need for surgery (relative risk, 0.58; 95% CI, 0.38-0.88; I2 = 11%), with moderate certainty.
CONCLUSIONS
Extended-use high-dose IV tranexamic acid does not improve mortality or bleeding outcomes and increases adverse events. Low-dose/enteral tranexamic acid may be effective in reducing hemorrhage; more evidence is required to demonstrate its safety.
Topics: Antifibrinolytic Agents; Gastrointestinal Hemorrhage; Humans; Length of Stay; Secondary Prevention; Tranexamic Acid
PubMed: 34709209
DOI: 10.1097/CCM.0000000000005362 -
Journal of the American College of... Jan 2023The efficacy and safety of direct oral anticoagulants (DOACs) for patients with thrombotic antiphospholipid syndrome remain controversial. (Meta-Analysis)
Meta-Analysis
BACKGROUND
The efficacy and safety of direct oral anticoagulants (DOACs) for patients with thrombotic antiphospholipid syndrome remain controversial.
OBJECTIVES
The authors performed a systematic review and meta-analysis of randomized controlled trials that compared DOACs with vitamin K antagonists (VKAs).
METHODS
We searched PubMed, EMBASE, and Cochrane Central Register of Controlled Trials through April 9, 2022. The 2 main efficacy outcomes were a composite of arterial thrombotic events and venous thromboembolic events (VTEs). The main safety outcome was major bleeding. Random effects models with inverse variance were used.
RESULTS
Our search retrieved 253 studies. Four open-label randomized controlled trials involving 472 patients were included (mean control-arm time-in-therapeutic-range 60%). All had proper random sequence generation and adequate allocation concealment. Overall, the use of DOACs compared with VKAs was associated with increased odds of subsequent arterial thrombotic events (OR: 5.43; 95% CI: 1.87-15.75; P < 0.001, I = 0%), especially stroke, and the composite of arterial thrombotic events or VTE (OR: 4.46; 95% CI: 1.12-17.84; P = 0.03, I = 0%). The odds of subsequent VTE (OR: 1.20; 95% CI: 0.31-4.55; P = 0.79, I = 0%), or major bleeding (OR: 1.02; 95% CI: 0.42-2.47; P = 0.97; I = 0%) were not significantly different between the 2 groups. Most findings were consistent within subgroups.
CONCLUSIONS
Patients with thrombotic antiphospholipid syndrome randomized to DOACs compared with VKAs appear to have increased risk for arterial thrombosis. No significant differences were observed between patients randomized to DOACs vs VKAs in the risk of subsequent VTE or major bleeding.
Topics: Humans; Administration, Oral; Anticoagulants; Antiphospholipid Syndrome; Fibrinolytic Agents; Hemorrhage; Randomized Controlled Trials as Topic; Thrombosis; Venous Thromboembolism; Vitamin K
PubMed: 36328154
DOI: 10.1016/j.jacc.2022.10.008 -
Frontiers in Public Health 2022Vitamin K (VK) as a nutrient, is a cofactor in the carboxylation of osteocalcin (OC), which can bind with hydroxyapatite to promote bone mineralization and increase bone... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Vitamin K (VK) as a nutrient, is a cofactor in the carboxylation of osteocalcin (OC), which can bind with hydroxyapatite to promote bone mineralization and increase bone strength. However, some studies have been inconsistent on whether vitamin K2 (VK2) can maintain or improve bone mineral density (BMD) and reduce the incidence of fractures in postmenopausal women. Therefore, the main objective of this meta-analysis was to determine the effect of VK2 as a nutritional supplement on BMD and fracture incidence in postmenopausal women.
METHODS
We searched PubMed, EMBASE, and Cochrane Library databases (published before March 17, 2022) and then extracted and pooled data from all randomized controlled trials (RCTs) that met the inclusion criteria.
RESULTS
Sixteen RCTs with a total of 6,425 subjects were included in this meta-analysis. The overall effect test of 10 studies showed a significant improvement in lumbar spine BMD (BMD LS) ( = 0.006) with VK2. The subgroup analysis of VK2 combination therapy showed that BMD LS was significantly maintained and improved with the administration of VK2 ( = 0.03). The overall effect test of the six RCTs showed no significant difference in fracture incidence between the two groups (RR=0.96, P=0.65). However, after excluding one heterogeneous study, the overall effect test showed a significant reduction in fracture incidence with VK2 (RR = 0.43, = 0.01). In addition, this meta-analysis showed that VK2 reduced serum undercarboxylated osteocalcin (uc-OC) levels and the ratio of uc-OC to cOC in both subgroups of VK2 combined intervention and alone. However, for carboxylated osteocalcin (cOC), both subgroup analysis and overall effect test showed no significant effect of VK2 on it. And the pooled analysis of adverse reactions showed no significant difference between the VK2 and control groups (RR = 1.03, 95%CI 0.87 to 1.21, = 0.76).
CONCLUSIONS
The results of this meta-analysis seem to indicate that VK2 supplementation has a positive effect on the maintenance and improvement of BMD LS in postmenopausal women, and it can also reduce the fracture incidence, serum uc-OC levels and the ratio of uc-OC to cOC. In conclusion, VK2 can indirectly promote bone mineralization and increase bone strength.
Topics: Bone Density Conservation Agents; Female; Humans; Osteocalcin; Osteoporosis, Postmenopausal; Randomized Controlled Trials as Topic; Vitamin K 2
PubMed: 36033779
DOI: 10.3389/fpubh.2022.979649 -
Reproductive Biology and Endocrinology... Aug 2023This study aimed to clarify the effect of antioxidant vitamins supplementation on endometriosis-related pain. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This study aimed to clarify the effect of antioxidant vitamins supplementation on endometriosis-related pain.
METHODS
A systematic search of PubMed, Web of Science, Cochrane Library, Scopus, and China National Knowledge Infrastructure (CNK) databases was conducted to identify relevant studies published in English and Chinese up to 16 March 2023. The search terms used were "endometriosis" OR "endometrioma" OR "endometrium" AND "antioxidant" OR "Vitamin C" OR "Vitamin E" OR "Vitamin D" OR "25-OHD" OR "25(OH)D" OR "25-hydroxyvitamin D". Eligible studies were randomized controlled trials (RCTs) that assessed pain scores using the Visual Analogue Scale (VAS). Mean differences or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the effect of antioxidant vitamins supplementation on endometriosis. The quality of the included studies was assessed using the Cochrane Risk of Bias Tool. The study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines.
RESULTS
A total of 13 RCTs involving 589 patients were included in this meta-analysis. We identified 11 studies that evaluated the effect of antioxidant vitamins supplementation on endometriosis-related pain. The results indicated that the supplementation of antioxidant vitamins can effectively alleviate endometriosis-related pain. Subgroup analysis showed that the supplementation of vitamin E (with or without vitamin C) had a positive effect on improving clinical pelvic pain in patients with chronic pelvic pain. Conversely, supplementation of vitamin D was associated with a reduction in pelvic pain in endometriosis patients, but the difference was not statistically significant compared to the placebo. Additionally, we observed changes in oxidative stress markers following vitamin supplementation. Plasma malondialdehyde (MDA) concentration decreased in patients with endometriosis after antioxidant vitamin supplementation, and the plasma MDA level was inversely correlated with the time and dose of vitamin E and C supplementation. Furthermore, the inflammatory markers in peritoneal fluid, including RANTES, interleukin-6, and monocyte chemoattractant protein-1, significantly decreased after antioxidant therapy. These findings suggest that antioxidant vitamins may alleviate pain in endometriosis patients by reducing inflammation.
CONCLUSIONS
The included studies support the potential role of antioxidant vitamins in the management of endometriosis. Supplementation with antioxidant vitamins effectively reduced the severity of dysmenorrhea, improved dyspareunia and pelvic pain, and enhanced quality of life in these patients. Therefore, antioxidant vitamin therapy could be considered as an alternative treatment method, either alone or in combination with other approaches, for endometriosis-related pain.
TRIAL REGISTRATION
PROSPERO registration number: CRD42023415198.
Topics: Female; Humans; Antioxidants; Pelvic Pain; Vitamins; Endometriosis; Vitamin A; Ascorbic Acid; Vitamin K; Dietary Supplements
PubMed: 37644533
DOI: 10.1186/s12958-023-01126-1 -
Radiology Feb 2021Background The association of pulmonary embolism (PE) with deep vein thrombosis (DVT) in patients with coronavirus disease 2019 (COVID-19) remains unclear, and the... (Meta-Analysis)
Meta-Analysis
Background The association of pulmonary embolism (PE) with deep vein thrombosis (DVT) in patients with coronavirus disease 2019 (COVID-19) remains unclear, and the diagnostic accuracy of D-dimer tests for PE is unknown. Purpose To conduct meta-analysis of the study-level incidence of PE and DVT and to evaluate the diagnostic accuracy of D-dimer tests for PE from multicenter individual patient data. Materials and Methods A systematic literature search identified studies evaluating the incidence of PE or DVT in patients with COVID-19 from January 1, 2020, to June 15, 2020. These outcomes were pooled using a random-effects model and were further evaluated using metaregression analysis. The diagnostic accuracy of D-dimer tests for PE was estimated on the basis of individual patient data using the summary receiver operating characteristic curve. Results Twenty-seven studies with 3342 patients with COVID-19 were included in the analysis. The pooled incidence rates of PE and DVT were 16.5% (95% CI: 11.6, 22.9; = 0.93) and 14.8% (95% CI: 8.5, 24.5; = 0.94), respectively. PE was more frequently found in patients who were admitted to the intensive care unit (ICU) (24.7% [95% CI: 18.6, 32.1] vs 10.5% [95% CI: 5.1, 20.2] in those not admitted to the ICU) and in studies with universal screening using CT pulmonary angiography. DVT was present in 42.4% of patients with PE. D-dimer tests had an area under the receiver operating characteristic curve of 0.737 for PE, and D-dimer levels of 500 and 1000 μg/L showed high sensitivity (96% and 91%, respectively) but low specificity (10% and 24%, respectively). Conclusion Pulmonary embolism (PE) and deep vein thrombosis (DVT) occurred in 16.5% and 14.8% of patients with coronavirus disease 2019 (COVID-19), respectively, and more than half of patients with PE lacked DVT. The cutoffs of D-dimer levels used to exclude PE in preexisting guidelines seem applicable to patients with COVID-19. © RSNA, 2020 See also the editorial by Woodard in this issue.
Topics: Humans; Computed Tomography Angiography; COVID-19; Fibrin Fibrinogen Degradation Products; Pulmonary Embolism; SARS-CoV-2; Venous Thrombosis; Multicenter Studies as Topic
PubMed: 33320063
DOI: 10.1148/radiol.2020203557 -
American Journal of Hematology Jul 2020COVID-19 is a systemic infection with a significant impact on the hematopoietic system and hemostasis. Lymphopenia may be considered as a cardinal laboratory finding,...
COVID-19 is a systemic infection with a significant impact on the hematopoietic system and hemostasis. Lymphopenia may be considered as a cardinal laboratory finding, with prognostic potential. Neutrophil/lymphocyte ratio and peak platelet/lymphocyte ratio may also have prognostic value in determining severe cases. During the disease course, longitudinal evaluation of lymphocyte count dynamics and inflammatory indices, including LDH, CRP and IL-6 may help to identify cases with dismal prognosis and prompt intervention in order to improve outcomes. Biomarkers, such high serum procalcitonin and ferritin have also emerged as poor prognostic factors. Furthermore, blood hypercoagulability is common among hospitalized COVID-19 patients. Elevated D-Dimer levels are consistently reported, whereas their gradual increase during disease course is particularly associated with disease worsening. Other coagulation abnormalities such as PT and aPTT prolongation, fibrin degradation products increase, with severe thrombocytopenia lead to life-threatening disseminated intravascular coagulation (DIC), which necessitates continuous vigilance and prompt intervention. So, COVID-19 infected patients, whether hospitalized or ambulatory, are at high risk for venous thromboembolism, and an early and prolonged pharmacological thromboprophylaxis with low molecular weight heparin is highly recommended. Last but not least, the need for assuring blood donations during the pandemic is also highlighted.
Topics: Anticoagulants; Betacoronavirus; Biomarkers; Blood Coagulation Tests; Blood Donors; C-Reactive Protein; COVID-19; COVID-19 Testing; Clinical Laboratory Techniques; Coronavirus Infections; Cytokine Release Syndrome; Cytokines; Disseminated Intravascular Coagulation; Early Diagnosis; Ferritins; Fibrin Fibrinogen Degradation Products; Humans; Lymphopenia; Meta-Analysis as Topic; Pandemics; Pneumonia, Viral; Risk; SARS-CoV-2; Thrombophilia; Venous Thromboembolism
PubMed: 32282949
DOI: 10.1002/ajh.25829 -
JAMA Surgery Apr 2021Tranexamic acid (TXA) is an efficient antifibrinolytic agent; however, concerns remain about the potential adverse effects, particularly vascular occlusive events, that...
IMPORTANCE
Tranexamic acid (TXA) is an efficient antifibrinolytic agent; however, concerns remain about the potential adverse effects, particularly vascular occlusive events, that may be associated with its use.
OBJECTIVE
To examine the association between intravenous TXA and total thromboembolic events (TEs) and mortality in patients of all ages and of any medical disciplines.
DATA SOURCE
Cochrane Central Register of Controlled Trials and MEDLINE were searched for eligible studies investigating intravenous TXA and postinterventional outcome published between 1976 and 2020.
STUDY SELECTION
Randomized clinical trials comparing intravenous TXA with placebo/no treatment. The electronic database search yielded a total of 782 studies, and 381 were considered for full-text review. Included studies were published in English, German, French, and Spanish. Studies with only oral or topical tranexamic administration were excluded.
DATA EXTRACTION AND SYNTHESIS
Meta-analysis, subgroup and sensitivity analysis, and meta-regression were performed. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline.
MAIN OUTCOMES AND MEASURES
Vascular occlusive events and mortality.
RESULTS
A total of 216 eligible trials including 125 550 patients were analyzed. Total TEs were found in 1020 (2.1%) in the group receiving TXA and 900 (2.0%) in the control group. This study found no association between TXA and risk for total TEs (risk difference = 0.001; 95% CI, -0.001 to 0.002; P = .49) for venous thrombosis, pulmonary embolism, venous TEs, myocardial infarction or ischemia, and cerebral infarction or ischemia. Sensitivity analysis using the risk ratio as an effect measure with (risk ratio = 1.02; 95% CI, 0.94-1.11; P = .56) and without (risk ratio = 1.03; 95% CI, 0.95-1.12; P = .52) studies with double-zero events revealed robust effect size estimates. Sensitivity analysis with studies judged at low risk for selection bias showed similar results. Administration of TXA was associated with a significant reduction in overall mortality and bleeding mortality but not with nonbleeding mortality. In addition, an increased risk for vascular occlusive events was not found in studies including patients with a history of thromboembolism. Comparison of studies with sample sizes of less than or equal to 99 (risk difference = 0.004; 95% CI, -0.006 to 0.014; P = .40), 100 to 999 (risk difference = 0.004; 95% CI, -0.003 to 0.011; P = .26), and greater than or equal to 1000 (risk difference = -0.001; 95% CI, -0.003 to 0.001; P = .44) showed no association between TXA and incidence of total TEs. Meta-regression of 143 intervention groups showed no association between TXA dosing and risk for venous TEs (risk difference, -0.005; 95% CI, -0.021 to 0.011; P = .53).
CONCLUSIONS AND RELEVANCE
Findings from this systematic review and meta-analysis of 216 studies suggested that intravenous TXA, irrespective of dosing, is not associated with increased risk of any TE. These results help clarify the incidence of adverse events associated with administration of intravenous TXA and suggest that TXA is safe for use with undetermined utility for patients receiving neurological care.
PubMed: 33851983
DOI: 10.1001/jamasurg.2021.0884 -
Pharmacological Research Feb 2023Medical nutrition treatment can manage diabetes and slow or prevent its complications. The comparative effects of micronutrient supplements, however, have not yet been... (Meta-Analysis)
Meta-Analysis Review
Comparative effects of vitamin and mineral supplements in the management of type 2 diabetes in primary care: A systematic review and network meta-analysis of randomized controlled trials.
Medical nutrition treatment can manage diabetes and slow or prevent its complications. The comparative effects of micronutrient supplements, however, have not yet been well established. We aimed at evaluating the comparative effects of vitamin and mineral supplements on managing glycemic control and lipid metabolism for type 2 diabetes mellitus (T2DM) to inform clinical practice. Electronic and hand searches for randomized controlled trials (RCTs) were performed until June 1, 2022. We selected RCTs enrolling patients with T2DM who were treated with vitamin supplements, mineral supplements, or placebo/no treatment. Data were pooled via frequentist random-effects network meta-analyses. A total of 170 eligible trials and 14223 participants were included. Low to very low certainty evidence established chromium supplements as the most effective in reducing fasting blood glucose levels and homeostasis model assessment of insulin resistance (SUCRAs: 90.4% and 78.3%, respectively). Vitamin K supplements ranked best in reducing glycated hemoglobin A1c and fasting insulin levels (SUCRAs: 97.0% and 82.3%, respectively), with moderate to very low certainty evidence. Vanadium supplements ranked best in lowering total cholesterol levels with very low evidence certainty (SUCRAs:100%). Niacin supplements ranked best in triglyceride reductions and increasing high-density lipoprotein cholesterol levels with low to very low evidence certainty (SUCRAs:93.7% and 94.6%, respectively). Vitamin E supplements ranked best in reducing low-density lipoprotein cholesterol levels with very low evidence certainty (SUCRAs:80.0%). Our analyses indicated that micronutrient supplements, especially chromium, vitamin E, vitamin K, vanadium, and niacin supplements, may be more efficacious in managing T2DM than other micronutrients. Considering the clinical importance of these findings, new research is needed to get better insight into this issue.
Topics: Humans; Vitamins; Network Meta-Analysis; Vanadium; Niacin; Randomized Controlled Trials as Topic; Dietary Supplements; Minerals; Vitamin E; Micronutrients; Diabetes Mellitus, Type 2; Vitamin K; Chromium; Primary Health Care; Cholesterol
PubMed: 36638933
DOI: 10.1016/j.phrs.2023.106647