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International Journal of Environmental... Dec 2022In the United States, a significant amount of the population is affected by hyperlipidemia, which is associated with increased levels of serum low-density lipoprotein... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
In the United States, a significant amount of the population is affected by hyperlipidemia, which is associated with increased levels of serum low-density lipoprotein (LDL-C) and risk of cardiovascular disease. As of 2019, the guidelines set by the American College of Cardiology/American Heart Association advocate for the use of statins as the major contributor to lowering serum LDL-C. While proven to be effective, side effects, including muscle-related symptoms and new-onset diabetes mellitus, can make patients unable to tolerate statin therapy. Additionally, there is a subset of the population which does not approach a recommended LDL-C goal on statin treatment. Due to these findings, it was deemed necessary to review the literature of current statin-alternative lipid-lowering therapies.
METHODS
A systematic review of preclinical and clinical papers, and a current meta-analysis, was performed using PubMed and Google Scholar. Following the literature review, a meta-analysis was conducted using ProMeta 3.
RESULTS
Through systematic review and meta-analysis of the current literature, it is suggested that newer lipid-lowering therapies such as proprotein convertase subtilsin-kixen type 9 (PCSK9) inhibitors are a safe and effective statin alternative for the population with statin intolerance. PCSK9 inhibitors were shown to have no significant effect in causing myalgia in patients and showed no increase in adverse cardiovascular outcomes compared to a control of a current antilipemic medication regimen.
DISCUSSION
There are many statin-alternative therapies that should be investigated further as a potential replacement for patients with statin intolerance or as an addition for patients with statin resistance.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Proprotein Convertase 9; PCSK9 Inhibitors; Cholesterol, LDL; Cardiovascular Diseases; Anticholesteremic Agents
PubMed: 36554779
DOI: 10.3390/ijerph192416899 -
Diabetology & Metabolic Syndrome 2018Recently, neck circumference (NC) has been used to predict the risk of cardiometabolic factors. This study aimed to perform a systematic review and meta-analysis to... (Review)
Review
BACKGROUND
Recently, neck circumference (NC) has been used to predict the risk of cardiometabolic factors. This study aimed to perform a systematic review and meta-analysis to examine: (i) the sensitivity (SE) and specificity (SP) of NC to predict cardiometabolic risk factors and (ii) the association between NC and the risk of cardiometabolic parameters.
METHODS
A systematic search was conducted through PubMed/Medline, Institute of Scientific Information, and Scopus, until 2017 based on the search terms of metabolic syndrome (MetS) and cardio metabolic risk factors. Random-effect model was used to perform a meta-analysis and estimate the pooled SE, SP and correlation coefficient (CC).
RESULTS
A total of 41 full texts were selected for systematic review. The pooled SE of greater NC to predict MetS was 65% (95% CI 58, 72) and 77% (95% CI 55, 99) in adult and children, respectively. Additionally, the pooled SP was 66% (95% CI 60, 72) and 66% (95% CI 48, 84) in adult and children, respectively. According to the results of meta-analysis in adults, NC had a positive and significant correlation with fasting blood sugar (FBS) (CC: 0.16, 95% CI 0.13, 0.20), HOMA-IR (0.38, 95% CI 0.25, 0.50), total cholesterol (TC) (0.07 95% CI 0.02, 0.12), triglyceride (TG) concentrations (0.23, 95% CI 0.19, 0.28) and low density lipoprotein cholesterol (LDL-C) (0.14, 95% CI 0.07, 0.22). Among children, NC was positively associated with FBS (CC: 0.12, 95% CI 0.07, 0.16), TG (CC: 0.21, 95% CI 0.17, 0.25), and TC concentrations (CC: 0.07, 95% CI 0.02, 0.12). However, it was not significant for LDL-C.
CONCLUSION
NC has a good predictive value to identify some cardiometabolic risk factors. There was a positive association between high NC and most cardiometabolic risk factors. However due to high heterogeneity, findings should be declared with caution.
PubMed: 30288175
DOI: 10.1186/s13098-018-0373-y -
Frontiers in Endocrinology 2022(1) To establish the prevalence of sleep disorders in women with PCOS. (2) To establish the association between sleep disturbance and cardiovascular risk factors in... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
(1) To establish the prevalence of sleep disorders in women with PCOS. (2) To establish the association between sleep disturbance and cardiovascular risk factors in women with PCOS.
METHODS
The electronic databases PubMed and EMBASE were searched for observational studies of individuals with PCOS published in English from inception to 21 October 2021. The dichotomous outcome measure was presented as odds ratio (OR) and 95% confidence interval (CI). The mean difference (MD) in continuous variables was expressed for each study.
RESULTS
A total of 18 articles were included in this meta-analysis, with a total of 16,152 participants from nine different countries. Women with PCOS had a high prevalence of sleep disturbance (OR = 6.22; 95% CI: 2.77, 13.97; < 0.001), higher PSQI scores (MD = 2.10; 95% CI: 0.29, 3.90; = 0.02), and shorter duration of sleep (MD = -15.65 min; 95% CI: -27.18, -4.13; = 0.008). We found that body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), low-density lipoprotein cholesterol (LDL-c), fasting glucose, 2-h glucose, and waist circumference (WC) levels were significantly higher and high-density lipoprotein cholesterol (HDL-c) was significantly lower in PCOS with sleep disturbance than in PCOS without sleep disturbance.
CONCLUSIONS
The current study shows a high prevalence of sleep disturbance in women with PCOS and provides evidence of an association between cardiovascular risk factors and sleep disturbance among this population. Increased attention should be paid to sleep management in clinical guidelines for PCOS.
UNLABELLED
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022298040.
Topics: Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Female; Glucose; Heart Disease Risk Factors; Humans; Polycystic Ovary Syndrome; Risk Factors; Sleep Quality; Sleep Wake Disorders
PubMed: 36176474
DOI: 10.3389/fendo.2022.971604 -
Journal of Bone Metabolism Feb 2021Research on osteoporosis and physical activity often focuses on women. We aimed to conduct a systematic review to assess the benefits and harms of physical activity...
BACKGROUND
Research on osteoporosis and physical activity often focuses on women. We aimed to conduct a systematic review to assess the benefits and harms of physical activity interventions for men's bone health.
METHODS
We used standard methods and searched for randomized controlled trials (RCTs) (duration, ≥6 months) published in all languages across multiple databases and trial registries. The last search was conducted on July 22, 2020.
RESULTS
We included 11 studies (14 publications), resulting in a sample of N=723 men (range, 17-132 participants). We found low-certainty evidence that physical activity has little influence on the areal bone mineral density (aBMD) at the total hip (5 RCTs, N=324; mean difference [MD], 0.03 [95 confidence interval (CI), 0.01 to 0.05]) and little or no influence on the aBMD at the femoral neck (3 RCTs, N=186; MD, 0.00 [95% CI, -0.04 to 0.04]), lumbar spine (3 RCTs; N=213; MD, 0.05 [95% CI, -0.01 to 0.11]), and whole body (4 RCTs, N=203; MD, -0.00 [95% CI, -0.03 to 0.02]).
CONCLUSIONS
We found low-certainty evidence that physical activity (≥6 months) has some effect on the total hip in men, but new evidence may change this finding. This review highlights the gap in the evidence on specific intervention prescriptions that can benefit the bone geometry, structure, microarchitecture, and, ultimately, bone strength in men. Future research should engage in comprehensive reporting of harms, quality of life outcomes, advanced imaging findings, and long-term interventions.
PubMed: 33730781
DOI: 10.11005/jbm.2021.28.1.27 -
Autoimmunity Reviews Jun 2022We conducted a systematic review, on behalf of the EULAR Study Group on Microcirculation in Rheumatic Diseases (EULAR SG MC/RD), to investigate the value of nailfold... (Review)
Review
Standardised interpretation of capillaroscopy in autoimmune idiopathic inflammatory myopathies: A structured review on behalf of the EULAR study group on microcirculation in Rheumatic Diseases.
OBJECTIVE
We conducted a systematic review, on behalf of the EULAR Study Group on Microcirculation in Rheumatic Diseases (EULAR SG MC/RD), to investigate the value of nailfold videocapillaroscopy (NVC) in idiopathic inflammatory myopathies (IIM).
METHODS
Three electronic databases were systematically searched to find all relevant manuscripts reporting NVC outcomes in IIM patients. Articles were assessed based on study design, population, NVC methodology and description of NVC results. To allow comparison between the articles, all NVC results were interpreted according to standardised capillaroscopic terminology, as previously consented by the EULAR SG MC/RD and the Scleroderma Clinical Trials Consortium (SCTC) Group on Capillaroscopy.
RESULTS
Of the 653 identified records; five were retained after critical appraisal on title, abstract and manuscript level. A marked difference in NVC was observed between (juvenile) dermatomyositis [(j)DM] versus polymyositis, healthy controls and systemic sclerosis patients. In addition, reduced capillary density and scleroderma pattern seem to be associated with active disease in (j)DM, while immunosuppressive treatment appears to reduce NVC abnormalities.
CONCLUSION
This is the first systematic review investigating NVC in IIM, interpreting the results according to an international consented standardised manner, as proposed by the EULAR SG MC/RD and SCTC Group on Capillaroscopy. We can conclude that NVC presents a promising asset in the diagnosis of (j)DM. Moreover, NVC could be a biomarker for organ involvement and follow-up. Large multicentre prospective standardised studies are further needed to definitely describe associations with clinical and laboratory parameters in the different IIM subtypes.
Topics: Autoimmune Diseases; Capillaries; Dermatomyositis; Humans; Microcirculation; Microscopic Angioscopy; Myositis; Nails; Prospective Studies; Rheumatic Diseases; Scleroderma, Localized; Scleroderma, Systemic
PubMed: 35421608
DOI: 10.1016/j.autrev.2022.103087 -
Frontiers in Endocrinology 2022Novel atherogenic lipid indices, including non-high-density lipoprotein cholesterol (non-HDL-C) which is calculated by subtracting the HDL-C value from the total... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Novel atherogenic lipid indices, including non-high-density lipoprotein cholesterol (non-HDL-C) which is calculated by subtracting the HDL-C value from the total cholesterol level, atherogenic index (ratio between triglycerides (TG) and HDL-C concentrations (TG/HDL-C)), and Diff-C (calculated by subtracting low-density lipoprotein (LDL-C) from non-HDL-C), have been known as valuable predictors of dyslipidemia and subsequent cardiovascular diseases. Previous studies have reported the potential association of novel atherogenic lipid indices with metabolic syndrome (MetS). This meta-analysis aimed to assess the pooled association of novel atherogenic lipid indices with MetS or its components.
METHODS
A systematic search was conducted through PubMed, Scopus, and Web of Science (WoS) databases from January 2000 until March 2021 to evaluate the association of novel atherogenic lipid indices, including non-HDL-C, atherogenic index, and the difference between non-HDL-C and LDL-C (Diff-C) with MetS. Observational studies were included without any language restriction. As exclusive studies evaluating the association of non-HDL-C with metabolic syndrome (MetS) were eligible to be included in quantitative analyses, a random-effect meta-analysis was performed to pool the odds ratios (ORs). A stratified meta-analysis was performed based on the definition of MetS [Adult Treatment Panel (ATP) and International Diabetes Federation (IDF)] and the studied population.
RESULTS
Overall, 318 studies were retrieved from an initial systematic search. After screening, 18 and five studies were included in the qualitative and quantitative syntheses, respectively. Qualitative synthesis revealed an association between non-HDL-C, Diff-C, and atherogenic index with MetS and its components. Stratified meta-analysis showed that an increased non-HDL-C level was associated with an increased odds of MetS based on ATP criteria (OR: 3.77, 95% CI: 2.14-5.39) and IDF criteria (OR: 2.71, 95% CI: 1.98-3.44) in adults (OR: 3.53, 95% CI: 2.29-4.78) and in children (OR: 2.27, 95% CI: 1.65-2.90).
CONCLUSION
Novel atherogenic lipid indices, including atherogenic index, Diff-c, and non-HDL-C, are strongly associated with increased odds of MetS and its components. The indices could be considered as potential predictors of MetS and its components in clinical practice.
Topics: Adenosine Triphosphate; Adult; Child; Cholesterol; Cholesterol, LDL; Diabetes Mellitus; Humans; Metabolic Syndrome; Triglycerides
PubMed: 36176470
DOI: 10.3389/fendo.2022.957136 -
Archives of Rehabilitation Research and... Mar 2024This systematic review aims to determine the effects of exercise on bone and muscle health in men with low bone density. (Review)
Review
OBJECTIVE
This systematic review aims to determine the effects of exercise on bone and muscle health in men with low bone density.
DATA SOURCES
An electronic search in the following databases was performed: Medline, AMED, Embase, Scopus, and SPORTDiscus between January 1940 and September 2021.
STUDY SELECTION
Randomized or non-randomized trials involving any form of exercise in adult men with a densitometric diagnosis of osteoporosis or osteopenia and reported outcomes relating to bone or muscle health. Two independent reviewers screened 12,018 records, resulting in 13 eligible articles.
DATA EXTRACTION
One reviewer extracted data into a pre-formed table, including characteristics of the exercise intervention, population examined, and primary and secondary outcomes. Study quality was assessed by 2 independent reviewers using the Tool for assEssment of Study qualiTy and reporting in Exercise (TESTEX).
DATA SYNTHESIS
Thirteen publications, originating from 6 unique trials, were eligible for inclusion, which assessed the effect of resistance training, impact training, whole body vibration, and traditional Chinese exercises. Resistance training was the most effective: it stimulates the replacement of adipose tissue with muscle, and in some cases, improved bone density.
CONCLUSIONS
Exercise, especially resistance training, slowed down the natural progression of osteoporosis and sarcopenia in men. These benefits are reflected in enhancements to function, such as improved mobility and balance. Other exercise modalities, such as whole body vibration and traditional Chinese exercises, generated minimal improvements to bone health, strength, and balance.
PubMed: 38482104
DOI: 10.1016/j.arrct.2023.100313 -
Journal of Ophthalmic & Vision Research 2019To estimate the pooled prevalence and incidence of diabetic retinopathy (DR) in Iran and to investigate their correlations with the Human Development Index (HDI),... (Review)
Review
PURPOSE
To estimate the pooled prevalence and incidence of diabetic retinopathy (DR) in Iran and to investigate their correlations with the Human Development Index (HDI), healthcare access (i.e., density of specialists and sub-specialists), and methodological issues.
METHODS
Electronic databases such as PubMed, Embase, Scopus, Web of Science, Google Scholar, and local databases were searched for cohort and cross-sectional studies published prior to January 2018. Prevalence and incidence rates of DR were extracted from January 2000 to December 2017 and random effects models were used to estimate pooled effect sizes. The Joanna Briggs Institute critical appraisal tool was applied for quality assessment of eligible studies.
RESULTS
A total of 55,445 participants across 33 studies were included. The pooled prevalence (95% CI) of DR in diabetic clinics (22 studies), eye clinics (4 studies), and general population (7 studies) was 31.8% (24.5 to 39.2), 57.8% (50.2 to 65.3), and 29.6% (22.6 to 36.5), respectively. It was 7.4% (3.9 to 10.8) for proliferative DR and 7.1% (4.9 to 9.4) for clinically significant macular edema. The heterogeneity of individual estimates of prevalence was highly significant. HDI ( < 0.001), density of specialists ( = 0.004), subspecialists ( < 0.001), and sampling site ( = 0.041) were associated with heterogeneity after the adjustment for type of DR, duration of diabetes, study year, and proportion of diabetics with controlled HbA1C.
CONCLUSION
Human development and healthcare access were correlated with the prevalence of DR. Data were scarce on the prevalence of DR in less developed provinces. Participant recruitment in eye clinics might overestimate the prevalence of DR.
PubMed: 31660112
DOI: 10.18502/jovr.v14i3.4790 -
The Cochrane Database of Systematic... May 2023Osteoporosis is characterized by low bone mass and micro-architectural deterioration of bone tissue leading to increased bone fragility. In people with... (Review)
Review
BACKGROUND
Osteoporosis is characterized by low bone mass and micro-architectural deterioration of bone tissue leading to increased bone fragility. In people with beta-thalassaemia, osteoporosis represents an important cause of morbidity and is due to a number of factors. First, ineffective erythropoiesis causes bone marrow expansion, leading to reduced trabecular bone tissue with cortical thinning. Second, excessive iron loading causes endocrine dysfunction, leading to increased bone turnover. Lastly, disease complications can result in physical inactivity, with a subsequent reduction in optimal bone mineralization. Treatments for osteoporosis in people with beta-thalassaemia include bisphosphonates (e.g. clodronate, pamidronate, alendronate; with or without hormone replacement therapy (HRT)), calcitonin, calcium, zinc supplementation, hydroxyurea, and HRT alone (for preventing hypogonadism). Denosumab, a fully human monoclonal antibody, inhibits bone resorption and increases bone mineral density (BMD). Finally, strontium ranelate simultaneously promotes bone formation and inhibits bone resorption, thus contributing to a net gain in BMD, increased bone strength, and reduced fracture risk. This is an update of a previously published Cochrane Review.
OBJECTIVES
To review the evidence on the efficacy and safety of treatment for osteoporosis in people with beta-thalassaemia.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register, which includes references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also searched online trial registries. Date of most recent search: 4 August 2022.
SELECTION CRITERIA
Randomized controlled trials (RCTs) in people with beta-thalassaemia with: a BMD Z score below -2 standard deviations (SDs) for children aged under 15 years, adult males (aged 15 to 50 years) and premenopausal females aged over 15 years; or a BMD T score below -2.5 SDs for postmenopausal females and males aged over 50 years.
DATA COLLECTION AND ANALYSIS
Two review authors assessed the eligibility and risk of bias of the included RCTs, and extracted and analysed data. We assessed the certainty of the evidence using GRADE.
MAIN RESULTS
We included six RCTs (298 participants). Active interventions included bisphosphonates (3 trials, 169 participants), zinc supplementation (1 trial, 42 participants), denosumab (1 trial, 63 participants), and strontium ranelate (1 trial, 24 participants). The certainty of the evidence ranged from moderate to very low and was downgraded mainly due to concerns surrounding imprecision (low participant numbers), but also risk of bias issues related to randomization, allocation concealment, and blinding. Bisphosphonates versus placebo or no treatment Two RCTs compared bisphosphonates to placebo or no treatment. After two years, one trial (25 participants) found that alendronate and clodronate may increase BMD Z score compared to placebo at the femoral neck (mean difference (MD) 0.40, 95% confidence interval (CI) 0.22 to 0.58) and the lumbar spine (MD 0.14, 95% CI 0.05 to 0.23). One trial (118 participants) reported that neridronate compared to no treatment may increase BMD at the lumbar spine and total hip at six and 12 months; for the femoral neck, the study found increased BMD in the neridronate group at 12 months only. All results were of very low-certainty. There were no major adverse effects of treatment. Participants in the neridronate group reported less back pain; we considered this representative of improved quality of life (QoL), though the certainty of the evidence was very low. One participant in the neridronate trial (116 participants) sustained multiple fractures as a result of a traffic accident. No trials reported BMD at the wrist or mobility. Different doses of bisphosphonate compared One 12-month trial (26 participants) assessed different doses of pamidronate (60 mg versus 30 mg) and found a difference in BMD Z score favouring the 60 mg dose at the lumbar spine (MD 0.43, 95% CI 0.10 to 0.76) and forearm (MD 0.87, 95% CI 0.23 to 1.51), but no difference at the femoral neck (very low-certainty evidence). This trial did not report fracture incidence, mobility, QoL, or adverse effects of treatment. Zinc versus placebo One trial (42 participants) showed zinc supplementation probably increased BMD Z score compared to placebo at the lumbar spine after 12 months (MD 0.15, 95% CI 0.10 to 0.20; 37 participants) and 18 months (MD 0.34, 95% CI 0.28 to 0.40; 32 participants); the same was true for BMD at the hip after 12 months (MD 0.15, 95% CI 0.11 to 0.19; 37 participants) and 18 months (MD 0.26, 95% CI 0.21 to 0.31; 32 participants). The evidence for these results was of moderate certainty. The trial did not report BMD at the wrist, fracture incidence, mobility, QoL, or adverse effects of treatment. Denosumab versus placebo Based on one trial (63 participants), we are unsure about the effect of denosumab on BMD Z score at the lumbar spine, femoral neck, and wrist joint after 12 months compared to placebo (low-certainty evidence). This trial did not report fracture incidence, mobility, QoL, or adverse effects of treatment, but the investigators reported a reduction in bone pain measured on a visual analogue scale in the denosumab group after 12 months of treatment compared to placebo (MD -2.40 cm, 95% CI -3.80 to -1.00). Strontium ranelate One trial (24 participants) only narratively reported an increase in BMD Z score at the lumbar spine in the intervention group and no corresponding change in the control group (very low-certainty evidence). This trial also found a reduction in back pain measured on a visual analogue scale after 24 months in the strontium ranelate group compared to the placebo group (MD -0.70 cm (95% CI -1.30 to -0.10); we considered this measure representative of improved quality of life.
AUTHORS' CONCLUSIONS
Bisphosphonates may increase BMD at the femoral neck, lumbar spine, and forearm compared to placebo after two years' therapy. Zinc supplementation probably increases BMD at the lumbar spine and hip after 12 months. Denosumab may make little or no difference to BMD, and we are uncertain about the effect of strontium on BMD. We recommend further long-term RCTs on different bisphosphonates and zinc supplementation therapies in people with beta-thalassaemia-associated osteoporosis.
Topics: Adult; Child; Female; Male; Humans; Middle Aged; beta-Thalassemia; Alendronate; Pamidronate; Clodronic Acid; Denosumab; Osteoporosis; Diphosphonates; Fractures, Bone
PubMed: 37159055
DOI: 10.1002/14651858.CD010429.pub3 -
Taiwan Journal of Ophthalmology 2023The purpose of the study is to evaluate the safety and outcomes of corneal collagen cross-linking (CXL) and different CXL protocols in progressive keratoconus (PK)... (Review)
Review
Short- and long-term safety and efficacy of corneal collagen cross-linking in progressive keratoconus: A systematic review and meta-analysis of randomized controlled trials.
PURPOSE
The purpose of the study is to evaluate the safety and outcomes of corneal collagen cross-linking (CXL) and different CXL protocols in progressive keratoconus (PK) population at short and long-term.
MATERIALS AND METHODS
A systematic review and meta-analysis was conducted. A total of eight literature databases were searched (up to February 15, 2022). Randomized controlled trials (RCTs) comparing CXL versus placebo/control or comparing different CXL protocols in the PK population were included. The primary objective was assessment of outcomes of CXL versus placebo and comparison of different CXL protocols in terms of maximum keratometry (Kmax) or Kmax change from baseline (Δ), spherical equivalent, best corrected visual acuity (BCVA), and central corneal thickness (CCT) in both at short term (6 months) and long term (1, 2, and 3 year or more). The secondary objective was comparative evaluation of safety. For the meta-analysis, the RevMan5.3 software was used.
RESULTS
A total of 48 RCTs were included. Compared to control, CXL was associated with improvement in Δ Kmax at 1 year (4 RCTs, mean difference [MD], -1.78 [-2.71, -0.86], P = 0.0002) and 2 and 3 years (1 RCT); ΔBCVA at 1 year (7 RCTs, -0.10 [-0.14, -0.06], P < 0.00001); and Δ CCT at 1 year (2 RCTs) and 3 years (1 RCT). Compared to conventional CXL (C-CXL), deterioration in Δ Kmax, ΔBCVA and endothelial cell density was seen at long term in the transepithelial CXL (TE-CXL, chemical enhancer). Up to 2 years, there was no difference between TE-CXL using iontophoresis (T-ionto) and C-CXL. At 2 and 4 years, C-CXL performed better compared to accelerated CXL (A-CXL) in terms of improving Kmax. Although CCT was higher in the A-CXL arm at 2 years, there was no difference at 4 years. While exploring heterogeneity among studies, selection of control eye (fellow eye of the same patient vs. eye of different patient) and baseline difference in Kmax were important sources of heterogeneity.
CONCLUSION
CXL outperforms placebo/control in terms of enhancing Kmax and CCT, as well as slowing disease progression over time (till 3 years). T-ionto protocol, on the other hand, performed similarly to C-CXL protocol up to 2 years.
PubMed: 37484615
DOI: 10.4103/2211-5056.361974