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Breast (Edinburgh, Scotland) Dec 2022Mammographic density is a well-defined risk factor for breast cancer and having extremely dense breast tissue is associated with a one-to six-fold increased risk of... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Mammographic density is a well-defined risk factor for breast cancer and having extremely dense breast tissue is associated with a one-to six-fold increased risk of breast cancer. However, it is questioned whether this increased risk estimate is applicable to current breast density classification methods. Therefore, the aim of this study was to further investigate and clarify the association between mammographic density and breast cancer risk based on current literature.
METHODS
Medline, Embase and Web of Science were systematically searched for articles published since 2013, that used BI-RADS lexicon 5th edition and incorporated data on digital mammography. Crude and maximally confounder-adjusted data were pooled in odds ratios (ORs) using random-effects models. Heterogeneity regarding breast cancer risks were investigated using I statistic, stratified and sensitivity analyses.
RESULTS
Nine observational studies were included. Having extremely dense breast tissue (BI-RADS density D) resulted in a 2.11-fold (95% CI 1.84-2.42) increased breast cancer risk compared to having scattered dense breast tissue (BI-RADS density B). Sensitivity analysis showed that when only using data that had adjusted for age and BMI, the breast cancer risk was 1.83-fold (95% CI 1.52-2.21) increased. Both results were statistically significant and homogenous.
CONCLUSIONS
Mammographic breast density BI-RADS D is associated with an approximately two-fold increased risk of breast cancer compared to having BI-RADS density B in general population women. This is a novel and lower risk estimate compared to previously reported and might be explained due to the use of digital mammography and BI-RADS lexicon 5th edition.
Topics: Female; Humans; Breast Density; Breast Neoplasms; Mammography; Breast; Risk Factors
PubMed: 36183671
DOI: 10.1016/j.breast.2022.09.007 -
BMJ (Clinical Research Ed.) Apr 2020To determine the relative effectiveness of dietary macronutrient patterns and popular named diet programmes for weight loss and cardiovascular risk factor improvement... (Meta-Analysis)
Meta-Analysis
Comparison of dietary macronutrient patterns of 14 popular named dietary programmes for weight and cardiovascular risk factor reduction in adults: systematic review and network meta-analysis of randomised trials.
OBJECTIVE
To determine the relative effectiveness of dietary macronutrient patterns and popular named diet programmes for weight loss and cardiovascular risk factor improvement among adults who are overweight or obese.
DESIGN
Systematic review and network meta-analysis of randomised trials.
DATA SOURCES
Medline, Embase, CINAHL, AMED, and CENTRAL from database inception until September 2018, reference lists of eligible trials, and related reviews.
STUDY SELECTION
Randomised trials that enrolled adults (≥18 years) who were overweight (body mass index 25-29) or obese (≥30) to a popular named diet or an alternative diet.
OUTCOMES AND MEASURES
Change in body weight, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, systolic blood pressure, diastolic blood pressure, and C reactive protein at the six and 12 month follow-up.
REVIEW METHODS
Two reviewers independently extracted data on study participants, interventions, and outcomes and assessed risk of bias, and the certainty of evidence using the GRADE (grading of recommendations, assessment, development, and evaluation) approach. A bayesian framework informed a series of random effects network meta-analyses to estimate the relative effectiveness of the diets.
RESULTS
121 eligible trials with 21 942 patients were included and reported on 14 named diets and three control diets. Compared with usual diet, low carbohydrate and low fat diets had a similar effect at six months on weight loss (4.63 4.37 kg, both moderate certainty) and reduction in systolic blood pressure (5.14 mm Hg, moderate certainty 5.05 mm Hg, low certainty) and diastolic blood pressure (3.21 2.85 mm Hg, both low certainty). Moderate macronutrient diets resulted in slightly less weight loss and blood pressure reductions. Low carbohydrate diets had less effect than low fat diets and moderate macronutrient diets on reduction in LDL cholesterol (1.01 mg/dL, low certainty 7.08 mg/dL, moderate certainty 5.22 mg/dL, moderate certainty, respectively) but an increase in HDL cholesterol (2.31 mg/dL, low certainty), whereas low fat (-1.88 mg/dL, moderate certainty) and moderate macronutrient (-0.89 mg/dL, moderate certainty) did not. Among popular named diets, those with the largest effect on weight reduction and blood pressure in comparison with usual diet were Atkins (weight 5.5 kg, systolic blood pressure 5.1 mm Hg, diastolic blood pressure 3.3 mm Hg), DASH (3.6 kg, 4.7 mm Hg, 2.9 mm Hg, respectively), and Zone (4.1 kg, 3.5 mm Hg, 2.3 mm Hg, respectively) at six months (all moderate certainty). No diets significantly improved levels of HDL cholesterol or C reactive protein at six months. Overall, weight loss diminished at 12 months among all macronutrient patterns and popular named diets, while the benefits for cardiovascular risk factors of all interventions, except the Mediterranean diet, essentially disappeared.
CONCLUSIONS
Moderate certainty evidence shows that most macronutrient diets, over six months, result in modest weight loss and substantial improvements in cardiovascular risk factors, particularly blood pressure. At 12 months the effects on weight reduction and improvements in cardiovascular risk factors largely disappear.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42015027929.
Topics: Blood Pressure; Body Mass Index; Body Weight; Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Diet, Carbohydrate-Restricted; Diet, Fat-Restricted; Diet, Mediterranean; Humans; Network Meta-Analysis; Nutrients; Obesity; Randomized Controlled Trials as Topic; Risk Reduction Behavior; Weight Loss
PubMed: 32238384
DOI: 10.1136/bmj.m696 -
JAMA Network Open Dec 2019Vitamin D and calcium supplements are recommended for the prevention of fracture, but previous randomized clinical trials (RCTs) have reported conflicting results, with... (Review)
Review Meta-Analysis
IMPORTANCE
Vitamin D and calcium supplements are recommended for the prevention of fracture, but previous randomized clinical trials (RCTs) have reported conflicting results, with uncertainty about optimal doses and regimens for supplementation and their overall effectiveness.
OBJECTIVE
To assess the risks of fracture associated with differences in concentrations of 25-hydroxyvitamin D (25[OH]D) in observational studies and the risks of fracture associated with supplementation with vitamin D alone or in combination with calcium in RCTs.
DATA SOURCES
PubMed, EMBASE, Cochrane Library, and other RCT databases were searched from database inception until December 31, 2018. Searches were performed between July 2018 and December 2018.
STUDY SELECTION
Observational studies involving at least 200 fracture cases and RCTs enrolling at least 500 participants and reporting at least 10 incident fractures were included. Randomized clinical trials compared vitamin D or vitamin D and calcium with control.
DATA EXTRACTION AND SYNTHESIS
Two researchers independently extracted data according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and assessed possible bias. Rate ratios (RRs) were estimated using fixed-effects meta-analysis. Data extraction and synthesis took place between July 2018 and June 2019.
MAIN OUTCOMES AND MEASURES
Any fracture and hip fracture.
RESULTS
In a meta-analysis of 11 observational studies (39 141 participants, 6278 fractures, 2367 hip fractures), each increase of 10.0 ng/mL (ie, 25 nmol/L) in 25 (OH)D concentration was associated with an adjusted RR for any fracture of 0.93 (95% CI, 0.89-0.96) and an adjusted RR for hip fracture of 0.80 (95% CI, 0.75-0.86). A meta-analysis of 11 RCTs (34 243 participants, 2843 fractures, 740 hip fractures) of vitamin D supplementation alone (daily or intermittent dose of 400-30 000 IU, yielding a median difference in 25[OH]D concentration of 8.4 ng/mL) did not find a reduced risk of any fracture (RR, 1.06; 95% CI, 0.98-1.14) or hip fracture (RR, 1.14; 95% CI, 0.98-1.32), but these trials were constrained by infrequent intermittent dosing, low daily doses of vitamin D, or an inadequate number of participants. In contrast, a meta-analysis of 6 RCTs (49 282 participants, 5449 fractures, 730 hip fractures) of combined supplementation with vitamin D (daily doses of 400-800 IU, yielding a median difference in 25[OH]D concentration of 9.2 ng/mL) and calcium (daily doses of 1000-1200 mg) found a 6% reduced risk of any fracture (RR, 0.94; 95% CI, 0.89-0.99) and a 16% reduced risk of hip fracture (RR, 0.84; 95% CI, 0.72-0.97).
CONCLUSIONS AND RELEVANCE
In this systematic review and meta-analysis, neither intermittent nor daily dosing with standard doses of vitamin D alone was associated with reduced risk of fracture, but daily supplementation with both vitamin D and calcium was a more promising strategy.
Topics: Bone Density Conservation Agents; Bone and Bones; Calcitriol; Dietary Supplements; Fractures, Bone; Hip Fractures; Humans; Randomized Controlled Trials as Topic; Vitamin D
PubMed: 31860103
DOI: 10.1001/jamanetworkopen.2019.17789 -
BMJ (Clinical Research Ed.) Aug 2021To inform the update of the European Association for the Study of Diabetes clinical practice guidelines for nutrition therapy. (Meta-Analysis)
Meta-Analysis
Effect of low glycaemic index or load dietary patterns on glycaemic control and cardiometabolic risk factors in diabetes: systematic review and meta-analysis of randomised controlled trials.
OBJECTIVE
To inform the update of the European Association for the Study of Diabetes clinical practice guidelines for nutrition therapy.
DESIGN
Systematic review and meta-analysis of randomised controlled trials.
DATA SOURCES
Medline, Embase, and the Cochrane Library searched up to 13 May 2021.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Randomised controlled trials of three or more weeks investigating the effect of diets with low glycaemic index (GI)/glycaemic load (GL) in diabetes.
OUTCOME AND MEASURES
The primary outcome was glycated haemoglobin (HbA1c). Secondary outcomes included other markers of glycaemic control (fasting glucose, fasting insulin); blood lipids (low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), non-HDL-C, apo B, triglycerides); adiposity (body weight, BMI (body mass index), waist circumference), blood pressure (systolic blood pressure (SBP) and diastolic blood pressure (DBP)), and inflammation (C reactive protein (CRP)).
DATA EXTRACTION AND SYNTHESIS
Two independent reviewers extracted data and assessed risk of bias. Data were pooled by random effects models. GRADE (grading of recommendations assessment, development, and evaluation) was used to assess the certainty of evidence.
RESULTS
29 trial comparisons were identified in 1617 participants with type 1 and 2 diabetes who were predominantly middle aged, overweight, or obese with moderately controlled type 2 diabetes treated by hyperglycaemia drugs or insulin. Low GI/GL dietary patterns reduced HbA1c in comparison with higher GI/GL control diets (mean difference −0.31% (95% confidence interval −0.42 to −0.19%), P<0.001; substantial heterogeneity, I2=75%, P<0.001). Reductions occurred also in fasting glucose, LDL-C, non-HDL-C, apo B, triglycerides, body weight, BMI, systolic blood pressure (dose-response), and CRP (P<0.05), but not blood insulin, HDL-C, waist circumference, or diastolic blood pressure. A positive dose-response gradient was seen for the difference in GL and HbA1c and for absolute dietary GI and SBP (P<0.05). The certainty of evidence was high for the reduction in HbA1c and moderate for most secondary outcomes, with downgrades due mainly to imprecision.
CONCLUSIONS
This synthesis suggests that low GI/GL dietary patterns result in small important improvements in established targets of glycaemic control, blood lipids, adiposity, blood pressure, and inflammation beyond concurrent treatment with hyperglycaemia drugs or insulin, predominantly in adults with moderately controlled type 1 and type 2 diabetes. The available evidence provides a good indication of the likely benefit in this population.
STUDY REGISTRATION
ClinicalTrials.gov NCT04045938.
Topics: Cardiometabolic Risk Factors; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diet, Diabetic; Glycemic Control; Glycemic Index; Glycemic Load; Humans
PubMed: 34348965
DOI: 10.1136/bmj.n1651 -
Osteoporosis International : a Journal... Jul 2023The aim of this systematic review and meta-analysis was (1) to determine exercise effects on bone mineral density (BMD) in postmenopausal women and (2) to address the... (Meta-Analysis)
Meta-Analysis Review
Exercise training and bone mineral density in postmenopausal women: an updated systematic review and meta-analysis of intervention studies with emphasis on potential moderators.
The aim of this systematic review and meta-analysis was (1) to determine exercise effects on bone mineral density (BMD) in postmenopausal women and (2) to address the corresponding implication of bone and menopausal status or supervision in postmenopausal women. A comprehensive search of eight electronic databases according to the PRISMA statement up to August 9, 2022, included controlled exercise trials ≥ 6 months. BMD changes (standardized mean differences: SMD) at the lumbar spine (LS), femoral neck (FN), and total hip (TH) were considered as outcomes. Study group comparisons were conducted for osteopenia/osteoporosis versus normal BMD, early versus late postmenopausal women, and predominantly supervised versus predominantly non-supervised study arms. We applied an inverse heterogeneity (IVhet) model. In summary, 80 studies involving 94 training and 80 control groups with a pooled number of 5581 participants were eligible. The IVhet model determined SMDs of 0.29 (95% CI: 0.16-0.42), 0.27 (95% CI: 0.16-0.39), and 0.41 (95% CI: 0.30-0.52) for LS, FN, and THBMD, respectively. Heterogeneity between the trial results varied from low (I = 20%, TH BMD) to substantial (I = 68%, LS-BMD). Evidence for publication bias/small study effects was negligibly low (FN-, TH-BMD) to high (LSBMD). We observed no significant differences (p > .09) for exercise effects on LS-, FN-, or TH-BMD-LS between studies/study arms with or without osteopenia/osteoporosis, early versus late postmenopausal women, or predominantly supervised versus non-supervised exercise programs. Using robust statistical methods, the present work provides further evidence for a positive effect of exercise on BMD in postmenopausal women. Differences in bone status (osteopenia/osteoporosis versus normal bone), menopausal status (early versus late postmenopausal), and supervision (yes versus no) did not significantly affect the exercise effects on BMD at LS or proximal femur.
Topics: Female; Humans; Bone Density; Postmenopause; Osteoporosis, Postmenopausal; Exercise; Osteoporosis; Femur Neck; Lumbar Vertebrae
PubMed: 36749350
DOI: 10.1007/s00198-023-06682-1 -
Nutrients Dec 2020The rise in obesity has emphasised a focus on lifestyle and dietary habits. We aimed to address the debate between low-carbohydrate and low-fat diets and compare their... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The rise in obesity has emphasised a focus on lifestyle and dietary habits. We aimed to address the debate between low-carbohydrate and low-fat diets and compare their effects on body weight, low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), total cholesterol, and triglycerides in an adult population.
METHOD
Medline and Web of Science were searched for randomised controlled trials (RCTs) comparing low-fat and low-carbohydrate diets up to September 2019. Three independent reviewers extracted data. Risk of bias was assessed using the Cochrane tool. The meta-analysis was stratified by follow-up time using the random-effects models.
RESULTS
This meta-analysis of 38 studies assessed a total of 6499 adults. At 6-12 months, pooled analyses of mean differences of low-carbohydrate vs. low-fat diets favoured the low-carbohydrate diet for average weight change (mean difference -1.30 kg; 95% CI -2.02 to -0.57), HDL (0.05 mmol/L; 95% CI 0.03 to 0.08), and triglycerides (TG) (-0.10 mmol/L; -0.16 to -0.04), and favoured the low-fat diet for LDL (0.07 mmol/L; 95% CI 0.02 to 0.12) and total cholesterol (0.10 mmol/L; 95% CI 0.02 to 0.18). Conclusion and Relevance: This meta-analysis suggests that low-carbohydrate diets are effective at improving weight loss, HDL and TG lipid profiles. However, this must be balanced with potential consequences of raised LDL and total cholesterol in the long-term.
Topics: Adult; Cholesterol, HDL; Cholesterol, LDL; Diet, Carbohydrate-Restricted; Diet, Fat-Restricted; Humans; Lipids; Triglycerides; Weight Loss
PubMed: 33317019
DOI: 10.3390/nu12123774 -
Clinical Microbiology and Infection :... Mar 2023COVID-19 and antimicrobial resistance (AMR) are two intersecting global public health crises. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
COVID-19 and antimicrobial resistance (AMR) are two intersecting global public health crises.
OBJECTIVE
We aimed to describe the impact of the COVID-19 pandemic on AMR across health care settings.
DATA SOURCE
A search was conducted in December 2021 in WHO COVID-19 Research Database with forward citation searching up to June 2022.
STUDY ELIGIBILITY
Studies evaluating the impact of COVID-19 on AMR in any population were included and influencing factors were extracted. Reporting of enhanced infection prevention and control and/or antimicrobial stewardship programs was noted.
METHODS
Pooling was done separately for Gram-negative and Gram-positive organisms. Random-effects meta-analysis was performed.
RESULTS
Of 6036 studies screened, 28 were included and 23 provided sufficient data for meta-analysis. The majority of studies focused on hospital settings (n = 25, 89%). The COVID-19 pandemic was not associated with a change in the incidence density (incidence rate ratio 0.99, 95% CI: 0.67-1.47) or proportion (risk ratio 0.91, 95% CI: 0.55-1.49) of methicillin-resistant Staphylococcus aureus or vancomycin-resistant enterococci cases. A non-statistically significant increase was noted for resistant Gram-negative organisms (i.e. extended-spectrum beta-lactamase, carbapenem-resistant Enterobacterales, carbapenem or multi-drug resistant or carbapenem-resistant Pseudomonas aeruginosa or Acinetobacter baumannii, incidence rate ratio 1.64, 95% CI: 0.92-2.92; risk ratio 1.08, 95% CI: 0.91-1.29). The absence of reported enhanced infection prevention and control and/or antimicrobial stewardship programs initiatives was associated with an increase in gram-negative AMR (risk ratio 1.11, 95% CI: 1.03-1.20). However, a test for subgroup differences showed no statistically significant difference between the presence and absence of these initiatives (p 0.40).
CONCLUSION
The COVID-19 pandemic may have hastened the emergence and transmission of AMR, particularly for Gram-negative organisms in hospital settings. But there is considerable heterogeneity in both the AMR metrics used and the rate of resistance reported across studies. These findings reinforce the need for strengthened infection prevention, antimicrobial stewardship, and AMR surveillance in the context of the COVID-19 pandemic.
Topics: Humans; Anti-Bacterial Agents; Drug Resistance, Bacterial; Methicillin-Resistant Staphylococcus aureus; COVID-19; Carbapenems
PubMed: 36509377
DOI: 10.1016/j.cmi.2022.12.006 -
Health Technology Assessment... Jun 2020Fragility fractures are fractures that result from mechanical forces that would not ordinarily result in fracture.
BACKGROUND
Fragility fractures are fractures that result from mechanical forces that would not ordinarily result in fracture.
OBJECTIVES
The objectives were to evaluate the clinical effectiveness, safety and cost-effectiveness of non-bisphosphonates {denosumab [Prolia; Amgen Inc., Thousand Oaks, CA, USA], raloxifene [Evista; Daiichi Sankyo Company, Ltd, Tokyo, Japan], romosozumab [Evenity; Union Chimique Belge (UCB) S.A. (Brussels, Belgium) and Amgen Inc.] and teriparatide [Forsteo; Eli Lilly and Company, Indianapolis, IN, USA]}, compared with each other, bisphosphonates or no treatment, for the prevention of fragility fracture.
DATA SOURCES
For the clinical effectiveness review, nine electronic databases (including MEDLINE, EMBASE and the World Health Organization International Clinical Trials Registry Platform) were searched up to July 2018.
REVIEW METHODS
A systematic review and network meta-analysis of fracture and femoral neck bone mineral density were conducted. A review of published economic analyses was undertaken and a model previously used to evaluate bisphosphonates was adapted. Discrete event simulation was used to estimate lifetime costs and quality-adjusted life-years for a simulated cohort of patients with heterogeneous characteristics. This was done for each non-bisphosphonate treatment, a strategy of no treatment, and the five bisphosphonate treatments previously evaluated. The model was populated with effectiveness evidence from the systematic review and network meta-analysis. All other parameters were estimated from published sources. An NHS and Personal Social Services perspective was taken, and costs and benefits were discounted at 3.5% per annum. Fracture risk was estimated from patient characteristics using the QFracture (QFracture-2012 open source revision 38, Clinrisk Ltd, Leeds, UK) and FRAX (web version 3.9, University of Sheffield, Sheffield, UK) tools. The relationship between fracture risk and incremental net monetary benefit was estimated using non-parametric regression. A probabilistic sensitivity analysis and scenario analyses were used to assess uncertainty.
RESULTS
Fifty-two randomised controlled trials of non-bisphosphonates were included in the clinical effectiveness systematic review and an additional 51 randomised controlled trials of bisphosphonates were included in the network meta-analysis. All treatments had beneficial effects compared with placebo for vertebral, non-vertebral and hip fractures, with hazard ratios varying from 0.23 to 0.94, depending on treatment and fracture type. The effects on vertebral fractures and the percentage change in bone mineral density were statistically significant for all treatments. The rate of serious adverse events varied across trials (0-33%), with most between-group differences not being statistically significant for comparisons with placebo/no active treatment, non-bisphosphonates or bisphosphonates. The incremental cost-effectiveness ratios were > £20,000 per quality-adjusted life-year for all non-bisphosphonate interventions compared with no treatment across the range of QFracture and FRAX scores expected in the population eligible for fracture risk assessment. The incremental cost-effectiveness ratio for denosumab may fall below £30,000 per quality-adjusted life-year at very high levels of risk or for high-risk patients with specific characteristics. Raloxifene was dominated by no treatment (resulted in fewer quality-adjusted life-years) in most risk categories.
LIMITATIONS
The incremental cost-effectiveness ratios are uncertain for very high-risk patients.
CONCLUSIONS
Non-bisphosphonates are effective in preventing fragility fractures, but the incremental cost-effectiveness ratios are generally greater than the commonly applied threshold of £20,000-30,000 per quality-adjusted life-year.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42018107651.
FUNDING
This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in ; Vol. 24, No. 29. See the NIHR Journals Library website for further project information.
Topics: Bone Density Conservation Agents; Clinical Trials as Topic; Cost-Benefit Analysis; Denosumab; Diphosphonates; Humans; Osteoporotic Fractures; Quality-Adjusted Life Years; Raloxifene Hydrochloride; Teriparatide; Treatment Outcome
PubMed: 32588816
DOI: 10.3310/hta24290 -
BMJ (Clinical Research Ed.) Mar 2022To compare the efficacy of different statin treatments by intensity on levels of non-high density lipoprotein cholesterol (non-HDL-C) for the prevention of... (Meta-Analysis)
Meta-Analysis
Comparative effectiveness of statins on non-high density lipoprotein cholesterol in people with diabetes and at risk of cardiovascular disease: systematic review and network meta-analysis.
OBJECTIVE
To compare the efficacy of different statin treatments by intensity on levels of non-high density lipoprotein cholesterol (non-HDL-C) for the prevention of cardiovascular disease in people with diabetes.
DESIGN
Systematic review and network meta-analysis.
DATA SOURCES
Medline, Cochrane Central Register of Controlled Trials, and Embase from inception to 1 December 2021.
REVIEW METHODS
Randomised controlled trials comparing different types and intensities of statins, including placebo, in adults with type 1 or type 2 diabetes mellitus were included. The primary outcome was changes in levels of non-HDL-C, calculated from measures of total cholesterol and HDL-C. Secondary outcomes were changes in levels of low density lipoprotein cholesterol (LDL-C) and total cholesterol, three point major cardiovascular events (non-fatal stroke, non-fatal myocardial infarction, and death related to cardiovascular disease), and discontinuations because of adverse events. A bayesian network meta-analysis of statin intensity (low, moderate, or high) with random effects evaluated the treatment effect on non-HDL-C by mean differences and 95% credible intervals. Subgroup analysis of patients at greater risk of major cardiovascular events was compared with patients at low or moderate risk. The confidence in network meta-analysis (CINeMA) framework was applied to determine the certainty of evidence.
RESULTS
In 42 randomised controlled trials involving 20 193 adults, 11 698 were included in the meta-analysis. Compared with placebo, the greatest reductions in levels of non-HDL-C were seen with rosuvastatin at high (-2.31 mmol/L, 95% credible interval -3.39 to -1.21) and moderate (-2.27, -3.00 to -1.49) intensities, and simvastatin (-2.26, -2.99 to -1.51) and atorvastatin (-2.20, -2.69 to -1.70) at high intensity. Atorvastatin and simvastatin at any intensity and pravastatin at low intensity were also effective in reducing levels of non-HDL-C. In 4670 patients at greater risk of a major cardiovascular events, atorvastatin at high intensity showed the largest reduction in levels of non-HDL-C (-1.98, -4.16 to 0.26, surface under the cumulative ranking curve 64%). Simvastatin (-1.93, -2.63 to -1.21) and rosuvastatin (-1.76, -2.37 to -1.15) at high intensity were the most effective treatment options for reducing LDL-C. Significant reductions in non-fatal myocardial infarction were found for atorvastatin at moderate intensity compared with placebo (relative risk=0.57, confidence interval 0.43 to 0.76, n=4 studies). No significant differences were found for discontinuations, non-fatal stroke, and cardiovascular deaths.
CONCLUSIONS
This network meta-analysis indicated that rosuvastatin, at moderate and high intensity doses, and simvastatin and atorvastatin, at high intensity doses, were most effective at moderately reducing levels of non-HDL-C in patients with diabetes. Given the potential improvement in accuracy in predicting cardiovascular disease when reduction in levels of non-HDL-C is used as the primary target, these findings provide guidance on which statin types and intensities are most effective by reducing non-HDL-C in patients with diabetes.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42021258819.
Topics: Adult; Bayes Theorem; Cardiovascular Diseases; Cholesterol; Diabetes Mellitus, Type 2; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Network Meta-Analysis
PubMed: 35331984
DOI: 10.1136/bmj-2021-067731 -
The Cochrane Database of Systematic... Feb 2023Diabetic retinopathy (DR) is characterised by neurovascular degeneration as a result of chronic hyperglycaemia. Proliferative diabetic retinopathy (PDR) is the most... (Review)
Review
BACKGROUND
Diabetic retinopathy (DR) is characterised by neurovascular degeneration as a result of chronic hyperglycaemia. Proliferative diabetic retinopathy (PDR) is the most serious complication of DR and can lead to total (central and peripheral) visual loss. PDR is characterised by the presence of abnormal new blood vessels, so-called "new vessels," at the optic disc (NVD) or elsewhere in the retina (NVE). PDR can progress to high-risk characteristics (HRC) PDR (HRC-PDR), which is defined by the presence of NVD more than one-fourth to one-third disc area in size plus vitreous haemorrhage or pre-retinal haemorrhage, or vitreous haemorrhage or pre-retinal haemorrhage obscuring more than one disc area. In severe cases, fibrovascular membranes grow over the retinal surface and tractional retinal detachment with sight loss can occur, despite treatment. Although most, if not all, individuals with diabetes will develop DR if they live long enough, only some progress to the sight-threatening PDR stage. OBJECTIVES: To determine risk factors for the development of PDR and HRC-PDR in people with diabetes and DR.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; which contains the Cochrane Eyes and Vision Trials Register; 2022, Issue 5), Ovid MEDLINE, and Ovid Embase. The date of the search was 27 May 2022. Additionally, the search was supplemented by screening reference lists of eligible articles. There were no restrictions to language or year of publication. SELECTION CRITERIA: We included prospective or retrospective cohort studies and case-control longitudinal studies evaluating prognostic factors for the development and progression of PDR, in people who have not had previous treatment for DR. The target population consisted of adults (≥18 years of age) of any gender, sexual orientation, ethnicity, socioeconomic status, and geographical location, with non-proliferative diabetic retinopathy (NPDR) or PDR with less than HRC-PDR, diagnosed as per standard clinical practice. Two review authors independently screened titles and abstracts, and full-text articles, to determine eligibility; discrepancies were resolved through discussion. We considered prognostic factors measured at baseline and any other time points during the study and in any clinical setting. Outcomes were evaluated at three and eight years (± two years) or lifelong. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data from included studies using a data extraction form that we developed and piloted prior to the data collection stage. We resolved any discrepancies through discussion. We used the Quality in Prognosis Studies (QUIPS) tool to assess risk of bias. We conducted meta-analyses in clinically relevant groups using a random-effects approach. We reported hazard ratios (HR), odds ratios (OR), and risk ratios (RR) separately for each available prognostic factor and outcome, stratified by different time points. Where possible, we meta-analysed adjusted prognostic factors. We evaluated the certainty of the evidence with an adapted version of the GRADE framework. MAIN RESULTS: We screened 6391 records. From these, we identified 59 studies (87 articles) as eligible for inclusion. Thirty-five were prospective cohort studies, 22 were retrospective studies, 18 of which were cohort and six were based on data from electronic registers, and two were retrospective case-control studies. Twenty-three studies evaluated participants with type 1 diabetes (T1D), 19 with type 2 diabetes (T2D), and 17 included mixed populations (T1D and T2D). Studies on T1D included between 39 and 3250 participants at baseline, followed up for one to 45 years. Studies on T2D included between 100 and 71,817 participants at baseline, followed up for one to 20 years. The studies on mixed populations of T1D and T2D ranged from 76 to 32,553 participants at baseline, followed up for four to 25 years. We found evidence indicating that higher glycated haemoglobin (haemoglobin A1c (HbA1c)) levels (adjusted OR ranged from 1.11 (95% confidence interval (CI) 0.93 to 1.32) to 2.10 (95% CI 1.64 to 2.69) and more advanced stages of retinopathy (adjusted OR ranged from 1.38 (95% CI 1.29 to 1.48) to 12.40 (95% CI 5.31 to 28.98) are independent risk factors for the development of PDR in people with T1D and T2D. We rated the evidence for these factors as of moderate certainty because of moderate to high risk of bias in the studies. There was also some evidence suggesting several markers for renal disease (for example, nephropathy (adjusted OR ranged from 1.58 (95% CI not reported) to 2.68 (2.09 to 3.42), and creatinine (adjusted meta-analysis HR 1.61 (95% CI 0.77 to 3.36)), and, in people with T1D, age at diagnosis of diabetes (< 12 years of age) (standardised regression estimate 1.62, 95% CI 1.06 to 2.48), increased triglyceride levels (adjusted RR 1.55, 95% CI 1.06 to 1.95), and larger retinal venular diameters (RR 4.28, 95% CI 1.50 to 12.19) may increase the risk of progression to PDR. The certainty of evidence for these factors, however, was low to very low, due to risk of bias in the included studies, inconsistency (lack of studies preventing the grading of consistency or variable outcomes), and imprecision (wide CIs). There was no substantial and consistent evidence to support duration of diabetes, systolic or diastolic blood pressure, total cholesterol, low- (LDL) and high- (HDL) density lipoproteins, gender, ethnicity, body mass index (BMI), socioeconomic status, or tobacco and alcohol consumption as being associated with incidence of PDR. There was insufficient evidence to evaluate prognostic factors associated with progression of PDR to HRC-PDR. AUTHORS' CONCLUSIONS: Increased HbA1c is likely to be associated with progression to PDR; therefore, maintaining adequate glucose control throughout life, irrespective of stage of DR severity, may help to prevent progression to PDR and risk of its sight-threatening complications. Renal impairment in people with T1D or T2D, as well as younger age at diagnosis of diabetes mellitus (DM), increased triglyceride levels, and increased retinal venular diameters in people with T1D may also be associated with increased risk of progression to PDR. Given that more advanced DR severity is associated with higher risk of progression to PDR, the earlier the disease is identified, and the above systemic risk factors are controlled, the greater the chance of reducing the risk of PDR and saving sight.
Topics: Adult; Female; Humans; Male; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Glycated Hemoglobin; Prognosis; Prospective Studies; Retinal Hemorrhage; Retrospective Studies; Triglycerides; Vitreous Hemorrhage
PubMed: 36815723
DOI: 10.1002/14651858.CD013775.pub2