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Vaccines Nov 2023Pneumococcal pneumonia is an important cause of morbidity and mortality amongst patients with inflammatory arthritis. Vaccination is recommended by the National... (Review)
Review
BACKGROUND
Pneumococcal pneumonia is an important cause of morbidity and mortality amongst patients with inflammatory arthritis. Vaccination is recommended by the National Institute for Health and Care Excellence (NICE) but it remains unclear how vaccine efficacy is impacted by different immunosuppressive agents. Our objective was to compare the chance of a seroconversion following vaccination against pneumococcus in patients with inflammatory arthritis to that in the general population, as well as to compare the chance of seroconversion across different targeted therapies.
METHODS
We searched MEDLINE, Embase and the Cochrane Library databases from inception until 20 June 2023. We included randomized controlled trials and observational studies. Aggregate data were used to undertake a pairwise meta-analysis. Our primary outcome of interest was vaccine seroconversion. We accepted the definition of serological response reported by the authors of each study.
RESULTS
Twenty studies were identified in the systematic review (2807 patients) with ten reporting sufficient data to be included in the meta-analysis (1443 patients). The chance of seroconversion in patients receiving targeted therapies, relative to the general population, was 0.61 (95% CI 0.35 to 1.08). The reduced odds of response were skewed strongly by the effects of abatacept and rituximab with no difference between patients on TNF inhibitors (TNFis) or IL-6 inhibition and healthy controls. Within different inflammatory arthritis populations the findings remained consistent, with rituximab having the strongest negative impact on vaccine response. TNF inhibition monotherapy was associated with a greater chance of vaccine response compared with methotrexate (2.25 (95% CI 1.28 to 3.96)). JAK inhibitor (JAKi) studies were few in number and did not present comparable vaccine response endpoints to include in the meta-analysis. The information available does not suggest any significant detrimental effects of JAKi on vaccine response.
CONCLUSION
This updated meta-analysis confirms that, for most patients with inflammatory arthritis, pneumococcal vaccine can be administered with confidence and that it will achieve comparable seroconversion rates to the healthy population. Patients on rituximab were the group least likely to achieve a response and further research is needed to explore the value of multiple-course pneumococcal vaccination schedules in this population.
PubMed: 38006012
DOI: 10.3390/vaccines11111680 -
RMD Open Aug 2023To explore the comparative effectiveness of pharmacological interventions for hand osteoarthritis (OA). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To explore the comparative effectiveness of pharmacological interventions for hand osteoarthritis (OA).
METHODS
We systematically searched Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials from inception until 26 December 2021, for randomised trials of pharmacological interventions for people with hand OA. Two reviewers independently extracted study data and assessed the risk of bias. We calculated the effect sizes for pain (standardised mean differences) using Bayesian random effects models for network meta-analysis (NMA) and pairwise meta-analysis. Based on a pre-specified protocol, we prospectively registered the study at PROSPERO, CRD42021215393.
RESULTS
We included 72 trials with 7609 participants. 65 trials (n=5957) were eligible for the quantitative synthesis, investigating 29 pharmacological interventions. Oral non-steroidal anti-inflammatory drugs (NSAIDs) and oral glucocorticoids' NMA effect sizes were -0.18 (95% credible interval -0.36 to 0.02) and -0.54 (-0.83 to -0.24), respectively, compared with placebo, and the result was consistent when limiting evidence to the pairwise meta-analysis of trials without high risk of bias. Intra-articular hyaluronate, intra-articular glucocorticoids, hydroxychloroquine, and topical NSAIDs' NMA effect sizes were 0.22 (-0.08 to 0.51), 0.25 (0.00 to 0.51), -0.01 (-0.19 to 0.18), and -0.14 (-0.33 to 0.08), respectively, compared with placebo. Oral NSAIDs were inferior to oral glucocorticoids with an NMA effect size of 0.36 (0.01 to 0.72). No intervention was superior to placebo when stratifying for thumb and finger OA.
CONCLUSION
Oral NSAIDs and glucocorticoids are apparently effective pharmacological interventions in hand OA. Intra-articular therapies and topical NSAIDs were not superior to placebo.
Topics: Humans; Bayes Theorem; Glucocorticoids; Network Meta-Analysis; Anti-Inflammatory Agents, Non-Steroidal; Osteoarthritis; Randomized Controlled Trials as Topic
PubMed: 37734873
DOI: 10.1136/rmdopen-2023-003030 -
Scientific Reports Aug 2023What is the impact of switching between biologics and biosimilars of adalimumab, etanercept, and infliximab on efficacy and safety for rheumatoid arthritis? A systematic... (Meta-Analysis)
Meta-Analysis
Impact of switching between reference biologics and biosimilars of tumour necrosis factor inhibitors for rheumatoid arthritis: a systematic review and network meta-analysis.
What is the impact of switching between biologics and biosimilars of adalimumab, etanercept, and infliximab on efficacy and safety for rheumatoid arthritis? A systematic review and network meta-analysis were performed to compare switching and non-switching groups of treatments. Pooled Risk Relative (RR) or standardised mean differences (SMD) with 95% credible intervals (95% CrIs) were obtained. Seventeen randomized trials with a switching phase involving 6,562 patients were included. Results showed that a single switch from biologics to biosimilars compared to continuing biologics had comparable effects for primary and co-primary outcomes, the American College of Rheumatology criteria with 20% response (ACR20) (7 trials, 1,926 patients, RR 0.98, 95% CrIs 0.93 to 1.03) and the Health Assessment Questionnaire-Disability Index (HAQ-DI) (5 trials, 1,609 patients, SMD - 0.07, 95% CrIs - 0.23 to 0.1), and within the equivalence margins: ACR20 [RR 0.94, 1.06] and HAQ-DI [SMD - 0.22, 0.22]. The risk of treatment-emergent adverse events, discontinuation, and positive anti-drug antibodies were comparable after switching. Safety results were imprecise, and the follow-up period might not be sufficient to evaluate long-term effects, especially malignancies. Overall, the practice of single switching between approved biologics and biosimilars of Tumour Necrosis Factor inhibitors is efficacious and safe for rheumatoid arthritis.
Topics: Humans; Biosimilar Pharmaceuticals; Tumor Necrosis Factor Inhibitors; Network Meta-Analysis; Arthritis, Rheumatoid; Infliximab
PubMed: 37607959
DOI: 10.1038/s41598-023-40222-5 -
The Journal of Rheumatology May 2024To conduct a systematic review of the effectiveness and safety of pharmacological treatments for adult-onset Still disease (AOSD). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To conduct a systematic review of the effectiveness and safety of pharmacological treatments for adult-onset Still disease (AOSD).
METHODS
Six databases, 2 trial registries, and conference abstracts were searched from January 2012 to February 2023 for studies of pharmacological interventions in people with AOSD. Outcomes were rates of remission and response, discontinuation of concurrent treatments, complications of AOSD, and treatment-related adverse events. Risk of bias was assessed with the Cochrane risk of bias tool and the Joanna Briggs Institute tool for case series.
RESULTS
Forty-four studies evaluated treatments, including nonsteroidal antiinflammatory drugs (NSAIDs), corticosteroids (CS), conventional synthetic disease-modifying antirheumatic drugs (DMARDs), and biologic DMARDs (bDMARDs). For bDMARDs, tocilizumab (TCZ), anakinra (ANK), and canakinumab (CNK) had the most available data. Although 3 randomized controlled trials did not show statistically significant benefits of bDMARDs, metaanalyses showed high rates of complete remission and CS discontinuation. Complete remission was 80% (95% CI 59-92%, 36%), 73% (95% CI 58-84%, 66%), and 77% (95% CI 29-97%, 82%) and CS discontinuation was 57% (95% CI 29-81%, 66%), 47% (95% CI 18-78%, 79%), and 34% (95% CI 6-81%, 59%), respectively, for TCZ, ANK, and CNK. Studies with a higher proportion of patients previously treated with bDMARDs showed a trend toward lower rates of CS discontinuation ( = 0.05). The analyses had high clinical heterogeneity, largely because treatments were prescribed as different lines of therapy.
CONCLUSION
Evidence supports TCZ, ANK, and CNK therapy for AOSD. However, the magnitude of effect and comparative effectiveness of treatments is uncertain.
Topics: Adult; Humans; Adrenal Cortex Hormones; Anti-Inflammatory Agents, Non-Steroidal; Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Biological Products; Interleukin 1 Receptor Antagonist Protein; Remission Induction; Still's Disease, Adult-Onset; Treatment Outcome
PubMed: 38302170
DOI: 10.3899/jrheum.2023-0995 -
BMC Pediatrics Aug 2023Children in acute pain often receive inadequate pain relief, partly from difficulties administering injectable analgesics. A rapid-acting, intranasal (IN) analgesic may... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Children in acute pain often receive inadequate pain relief, partly from difficulties administering injectable analgesics. A rapid-acting, intranasal (IN) analgesic may be an alternative to other parenteral routes of administration. Our review compares the efficacy, safety, and acceptability of intranasal analgesia to intravenous (IV) and intramuscular (IM) administration; and to compare different intranasal agents.
METHODS
We searched Cochrane Library, MEDLINE/PubMed, Embase, Web of Knowledge, Clinicaltrials.gov, Controlled-trials.com/mrcr, Clinicaltrialsregister.eu, Apps.who.int/trialsearch. We also screened reference lists of included trials and relevant systematic reviews. Studies in English from any year were included. Two authors independently assessed all studies. We included randomised trials (RCTs) of children 0-16, with moderate to severe pain; comparing intranasal analgesia to intravenous or intramuscular analgesia, or to other intranasal agents. We excluded studies of procedural sedation or analgesia. We extracted study characteristics and outcome data and assessed risk of bias with the ROB 2.0-tool. We conducted meta-analysis and narrative review, evaluating the certainty of evidence using GRADE. Outcomes included pain reduction, adverse events, acceptability, rescue medication, ease of and time to administration.
RESULTS
We included 12 RCTs with a total of 1163 children aged 3 to 20, most below 10 years old, with a variety of conditions. Our review shows that: - There may be little or no difference in pain relief (single dose IN vs IV fentanyl MD 4 mm, 95% CI -8 to 16 at 30 min by 100 mm VAS; multiple doses IN vs IV fentanyl MD 0, 95%CI -0.35 to 0.35 at 15 min by Hannallah score; single dose IN vs IV ketorolac MD 0.8, 95% CI -0.4 to 1.9 by Faces Pain Scale-Revised), adverse events (single dose IN vs IV fentanyl RR 3.09, 95% CI 0.34 to 28.28; multiple doses IN vs IV fentanyl RR 1.50, 95%CI 0.29 to 7.81); single dose IN vs IV ketorolac RR 0.716, 95% CI 0.23 to 2.26), or acceptability (single dose IN vs IV ketorolac RR 0.83, 95% CI 0.66 to 1.04) between intranasal and intravenous analgesia (low certainty evidence). - Intranasal diamorphine or fentanyl probably give similar pain relief to intramuscular morphine (narrative review), and are probably more acceptable (RR 1.60, 95% CI 1.42 to 1.81) and tolerated better (RR 0.061, 95% CI 0.03 to 0.13 for uncooperative/negative reaction) (moderate certainty); adverse events may be similar (narrative review) (low certainty). - Intranasal ketamine gives similar pain relief to intranasal fentanyl (SMD 0.05, 95% CI -0.20 to 0.29 at 30 min), while having a higher risk of light sedation (RR 1.74, 95% CI 1.30 to 2.35) and mild side effects (RR 2.16, 95% CI 1.72 to 2.71) (high certainty). Need for rescue analgesia is probably similar (RR 0.85, 95% CI 0.62 to 1.17) (moderate certainty), and acceptability may be similar (RR 1.15, 95% CI 0.89 to 1.48) (low certainty).
CONCLUSIONS
Our review suggests that intranasal analgesics are probably a good alternative to intramuscular analgesics in children with acute moderate to severe pain; and may be an alternative to intravenous administration. Intranasal ketamine gives similar pain relief to fentanyl, but causes more sedation, which should inform the choice of intranasal agent.
Topics: Child; Humans; Ketorolac; Ketamine; Pain; Analgesia; Fentanyl
PubMed: 37596559
DOI: 10.1186/s12887-023-04203-x -
Neurological Sciences : Official... Oct 2023Neurological deterioration, soon after anti-copper treatment initiation, is problematic in the management of Wilson's disease (WD) and yet reports in the literature are... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Neurological deterioration, soon after anti-copper treatment initiation, is problematic in the management of Wilson's disease (WD) and yet reports in the literature are limited. The aim of our study was to systematically assess the data according to early neurological deteriorations in WD, its outcome and risk factors.
METHODS
Using PRISMA guidelines, a systematic review of available data on early neurological deteriorations was performed by searching the PubMed database and reference lists. Random effects meta-analytic models summarized cases of neurological deterioration by disease phenotype.
RESULTS
Across the 32 included articles, 217 cases of early neurological deterioration occurred in 1512 WD patients (frequency 14.3%), most commonly in patients with neurological WD (21.8%; 167/763), rarely in hepatic disease (1.3%; 5/377), and with no cases among asymptomatic individuals. Most neurological deterioration occurred in patients treated with d-penicillamine (70.5%; 153/217), trientine (14.2%; 31/217) or zinc salts (6.9%; 15/217); the data did not allow to determine if that reflects how often treatments were chosen as first line therapy or if the risk of deterioration differed with therapy. Symptoms completely resolved in 24.2% of patients (31/128), resolved partially in 27.3% (35/128), did not improve in 39.8% (51/128), with 11 patients lost to follow-up.
CONCLUSIONS
Given its occurrence in up to 21.8% of patients with neurological WD in this meta-analysis of small studies, there is a need for further investigations to distinguish the natural time course of WD from treatment-related early deterioration and to develop a standard definition for treatment-induced effects.
Topics: Humans; Hepatolenticular Degeneration; Penicillamine; Trientine; Copper; Nervous System Diseases
PubMed: 37311952
DOI: 10.1007/s10072-023-06895-6 -
PloS One 2023Some patients have insufficient treatment response to conventional disease-modifying antirheumatic drugs (cDMARD); although biologics have proven to be an effective... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVES
Some patients have insufficient treatment response to conventional disease-modifying antirheumatic drugs (cDMARD); although biologics have proven to be an effective treatment for RA, the effects that bDMARDs have on integumentary, cardiac, and immune systems and the high costs associated with these treatments, make that mesenchymal stem cell-based therapies (MSCs) for RA are being considered potential treatment methods. This work analyses the performance in safety and efficacy terms of MSCs techniques.
METHODS AND FINDING
A literature search was performed in PubMed, EMBASE, Cochrane Library, Web of Science, and Open Grey databases from inception to October 28, 2022. Three randomized controlled trials (RCTs) and one non-randomized controlled trial (non-RCTs), including 358 patients met our inclusion criteria and were included in qualitative synthesis; only RCTs were eligible for quantitative synthesis (meta-analysis). Meta-analysis of adverse events (AE) in RCTs showed no significant differences in the incidence of AE in the MSCs group compared to the control group (Risk ratio: 2.35; 95% CI, 0.58 to 9.58; I2 = 58.80%). The pooled Risk ratio for non-serious and serious adverse events showed no statistical difference between intervention and control groups concerning the incidence of non-serious and serious adverse events (Risk ratio: 2.35; 95% CI, 0.58 to 9.51; I2 = 58.62%) and (Risk ratio: 1.10; 95% CI, 0.15 to 7.97; I2 = 0.0%) respectively. The Health Assessment Questionnaire (HAQ) and Disease Activity Score (DAS28) decreased in agreement with the decreasing values of C-reactive protein (CRP) and Erythrocyte sedimentation rate (ESR). Additionally, a trend toward clinical efficacy was observed; however, this improvement was not shown in the studies after 12 months of follow-up without continuous treatment administration.
CONCLUSION
This Systematic review and meta-analysis showed a favorable safety profile, without life-threatening events in subjects with RA, and a trend toward clinical efficacy that must be confirmed through high-quality RCTs, considerable sample size, and extended follow-up in subjects with RA.
Topics: Humans; Antirheumatic Agents; Arthritis, Rheumatoid; Methotrexate; Treatment Outcome; Controlled Clinical Trials as Topic
PubMed: 37498842
DOI: 10.1371/journal.pone.0284828 -
European Journal of Medical Research Jul 2023Recent studies have shown that aspirin consumption may reduce the risk of hepatocellular carcinoma (HCC), but their correlation is still not fully understood. This... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Recent studies have shown that aspirin consumption may reduce the risk of hepatocellular carcinoma (HCC), but their correlation is still not fully understood. This meta-analysis aimed to investigate the correlation between aspirin consumption and HCC.
METHODS
A systematic literature search was conducted on PubMed, Scopus, Cochrane Library, EMBASE, and Web of Science databases. The search period was from the establishment of the database to July 1, 2022 with no language restrictions.
RESULTS
A total of 19 studies including three prospective studies and 16 retrospective ones with 2,217,712 patients were included. Compared with those who did not take aspirin, those who took aspirin had a 30% lower risk of HCC (hazard ratio [HR] = 0.70, 95% confidence interval [CI] 0.63-0.76, I = 84.7%, P < 0.001). Subgroup analysis showed that aspirin significantly reduced the risk of HCC by 19% in Asia (HR = 0.81, 95% CI 0.80-0.82, I = 85.2%, P < 0.001) and by 33% (HR = 0.67, 95% CI 0.61-0.73, I = 43.6%, P = 0.150) in Europe and the U.S with no significant difference. Moreover, in patients with HBV or HCV infection, aspirin reduced 19% and 24% of the risk of HCC, respectively. However, aspirin administration might increase risks of gastrointestinal bleeding in patients with chronic liver disease (HR = 1.14, 95% CI 0.99-1.31, I = 0.0%, P = 0.712). Sensitivity analysis showed no significant difference of results after excluding individual studies, suggesting that the results were robust.
CONCLUSION
Aspirin may reduce the risk of HCC in both healthy population and patients with chronic liver disease. However, attention should be paid to adverse events such as gastrointestinal bleeding in patients with chronic liver disease.
Topics: Humans; Carcinoma, Hepatocellular; Aspirin; Liver Neoplasms; Prospective Studies; Retrospective Studies; Gastrointestinal Hemorrhage
PubMed: 37422691
DOI: 10.1186/s40001-023-01204-5 -
Frontiers in Immunology 2023Pemphigus foliaceus (PF) differs from pemphigus vulgaris (PV) in that it affects only the skin and mucous membranes are not involved. Pemphigus is commonly treated with...
BACKGROUND
Pemphigus foliaceus (PF) differs from pemphigus vulgaris (PV) in that it affects only the skin and mucous membranes are not involved. Pemphigus is commonly treated with systemic corticosteroids and immunosuppressive agents (ISAs). More recently, biologics have been used. The current literature on biologic therapy often combines treatment of PF with PV, hence it is often difficult for clinicians to isolate the treatment of PF from PV. The purpose of this review was to provide information regarding the use of current biological therapy, specifically in PF.
MATERIALS AND METHODS
A search of PubMed, Embase, and other databases was conducted using keywords pemphigus foliaceus (PF), rituximab (RTX), intravenous immunoglobulin (IVIg), and biologics. Forty-one studies were included in this review, which produced 105 patients with PF, treated with RTX, IVIg, or a combination of both. Eighty-five patients were treated with RTX, eight patients with IVIg, and 12 received both RTX and IVIg.
RESULTS
Most patients in this review had PF that was nonresponsive to conventional immunosuppressive therapies (CIST), and had significant side effects from their use. RTX treatment resulted in complete remission (CR) in 63.2%, a relapse rate of 39.5%, an infection rate of 19.7%, and a mortality rate of 3.9%. Relapse was greater in the lymphoma (LP) protocol than the rheumatoid arthritis (RA) protocol (p<0.0001). IVIg led to CR in 62.5% of patients, with no relapses or infections. Patients receiving both biologics experienced better outcomes when RTX was first administered, then followed by IVIg. Follow-up durations for patients receiving RTX, IVIg, and both were 22.1, 24.8, and 35.7 months, respectively.
DISCUSSION
In pemphigus foliaceus patients nonresponsive to conventional immunosuppressive therapy or in those with significant side effects from CIST, RTX and IVIg appear to be useful agents. Profile of clinical response, as well as relapse, infection, and mortality rates in PF patients treated with RTX were similar to those observed in PV patients. The data suggests that protocols specific for PF may produce better outcomes, less adverse effects, and improved quality of life.
Topics: Humans; Pemphigus; Immunoglobulins, Intravenous; Quality of Life; Immunosuppressive Agents; Rituximab; Recurrence; Biological Products
PubMed: 37901249
DOI: 10.3389/fimmu.2023.1267668 -
Complementary Therapies in Medicine Mar 2024Curcumin has antioxidant properties and has been proposed as a potential treatment for NAFLD. The aim of current systematic review and meta-analysis was to evaluate... (Meta-Analysis)
Meta-Analysis
Curcumin effects on glycaemic indices, lipid profile, blood pressure, inflammatory markers and anthropometric measurements of non-alcoholic fatty liver disease patients: A systematic review and meta-analysis of randomized clinical trials.
OBJECTIVES
Curcumin has antioxidant properties and has been proposed as a potential treatment for NAFLD. The aim of current systematic review and meta-analysis was to evaluate previous findings for the effect of curcumin supplementation on glycaemic indices, lipid profile, blood pressure, inflammatory markers, and anthropometric measurements of NAFLD patients.
METHODS
Relevant studies published up to January 2024 were searched systematically using the following databases: PubMed, SCOPUS, WOS, Science Direct, Ovid and Cochrane. The systematic review and meta-analysis were conducted according to the 2020 PRISMA guidelines. The quality of the papers was assessed the using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist. Pooled effect sizes were calculated using a random-effects model and reported as the WMD and 95% CI. Also, subgroup analyses were done to find probable sources of heterogeneity among studies.
RESULTS
Out of 21010 records initially identified, 21 eligible RCTs were selected for inclusion in a meta-analysis. Overall, 1191 participants of both genders, 600 in the intervention and 591 in the control group with NAFLD were included. There are several limitations in the studies that were included, for instance, the results are weakened substantially by potential bias or failure to account for potential adulteration (with pharmaceuticals) or contamination (with other herbs) of the curcumin supplements that were tested. However, previous studies have reported curcumin to be a safe complementary therapy for several conditions. Our study indicated that curcumin supplementation in doses of 50-3000 mg/day was associated with significant change in FBG [WMD: -2.83; 95% CI: -4.61, -1.06), I = 51.3%], HOMA-IR [WMD: -0.52; 95% CI: -0.84, -0.20), I= 82.8%], TG [WMD: -10.31; 95% CI: -20.00, -0.61), I = 84.5%], TC [WMD: -11.81; 95% CI: -19.65, -3.96), I = 94.6%], LDL [WMD: -8.01; 95% CI: -15.79, -0.24), I = 96.1%], weight [WMD: -0.81; 95% CI: -1.28, -0.35), I= 0.0%] and BMI [WMD: -0.35; 95% CI: -0.57, -0.13), I= 0.0%] in adults with NAFLD. There was no significant change in HbA1C, plasma insulin, QUICKI, HDL, SBP, DBP, CRP, TNF-α and WC after curcumin therapy. Subgroup analysis suggested a significant changes in serum FBG, TG, SBP, WC in RCTs for intervention durations of ≥ 8 weeks, and SBP, TG, LDL, HDL, BMI, WC in RCTs with sample size > 55 participants.
CONCLUSION
Curcumin supplementation in doses of 50-3000 mg/day over 8-12 weeks was associated with significant reductions in levels of FBG, HOMA-IR, TG, TC, LDL, weight and BMI in patients with NAFLD. Previous studies have reported curcumin as a safe complementary therapy for several diseases. We would suggest that should curcumin supplements be used clinically in specific conditions, it should be used with caution. Also, difference in grades of NAFLD may effect the evaluated outcomes, so it is suggested that future studies be conducted with an analyses on subgroups according to their NAFLD grade. Furthermore, because of the failure to conduct independent biochemical assessment of the turmeric/curcumin product used in most studies as well as potential sources of bias, results should be interpreted with caution.
Topics: Adult; Female; Humans; Male; Blood Pressure; Curcumin; Dietary Supplements; Glycemic Index; Lipids; Non-alcoholic Fatty Liver Disease; Randomized Controlled Trials as Topic
PubMed: 38232906
DOI: 10.1016/j.ctim.2024.103025