A Simple Guide to Systematic Reviews and Meta-Analyses.

Systematic reviews and meta-analyses lie on the top of the evidence hierarchy because they utilize explicit methods for literature search and retrieval of studies relevant to the review question as well as robust methodology for quality assessment of included studies and quantitative synthesis of results. As opposed to narrative reviews which represent the authors' personal judgments, they may be more resource-intensive, but provide an unbiased answer to a specific clinical query. Clinical guidelines are usually supported by such evidence syntheses. Therefore, it is important that healthcare practitioners become competent in understanding and applying systematic review findings. This simple guide outlines the key principles regarding the design, conduct and interpretation of systematic reviews and meta-analyses.

Pulmonary exacerbations, airway pathogens, and long-term course of lung clearance index in children and young adults with cystic fibrosis.

BACKGROUND: Pulmonary exacerbations (PEx), pathogens colonizing the respiratory tract, and patients' age are associated with progressive worsening of lung function among patients with cystic fibrosis (CF). However, the effect of these factors on longitudinal changes of Lung Clearance Index (LCI) remains unclear. AIM: To assess the role of age, different types of bronchial infection, and PEx on LCI deterioration. METHODS: We conducted a retrospective study assessing multiple-breath washout (MBW) and spirometry changes among CF patients evaluated at quarterly outpatient clinic visits over 8 years. MBW and spirometry were performed at each visit, sputum samples and/or cough swabs were obtained for culture, whereas respiratory symptoms and clinical examination findings were recorded. Patients who had ≥5 serial MBW measurements, one of which coincided with a pulmonary exacerbation, were reviewed. RESULTS: Seventy-six patients were included in the study: mean age of 10.61 years (range 1.75-23.75). A total of 1152 MBW tests and 1047 spirometry tests were performed. LCI was significantly higher among CF patients aged 11-15, 16-20, and over 20 years than those under 5 years of age; ΔLCI: 1.16 (confidence interval [CI] 0.43-1.90) and 3.25 (CI 2.33-4.17), respectively. Furthermore, LCI was significantly elevated in CF patients with positive cultures for Pseudomonas aeruginosa (0.52 LCI [CI -0.12 to 0.71]) and Stenotrophomonas Maltophilia (1.41 LCI [CI 0.61-2.21]). Moreover, increased values of LCI in CF patients were significantly associated with increased risk of PEx (odds ratio [OR] 1.19, CI [1.14-1.25], p < 0.001). CONCLUSION: LCI demonstrates a progression of lung disease and corresponds to changes in bacterial infections and PEx among patients with CF. LCI may be a valuable marker for tracking disease deterioration and may have a role in the routine clinical care of patients with CF.

Comparative efficacy of glucose-lowering medications on body weight and blood pressure in patients with type 2 diabetes: A systematic review and network meta-analysis.

AIM: To compare the effects of glucose-lowering drugs on body weight and blood pressure in adults with type 2 diabetes. METHODS: We searched Medline, Embase, the Cochrane Library, and grey literature sources until 29 September 2020 for randomized controlled trials of at least 24 weeks' duration assessing the effects of glucose-lowering drugs on body weight and blood pressure in adults with type 2 diabetes. We performed frequentist network meta-analyses and calculated weighted mean differences and 95% confidence intervals combining trial arms of different approved doses of a given intervention into a single group. We evaluated the confidence in pooled estimates using the CINeMA (Confidence In Network Meta-Analysis) framework. RESULTS: In total, 424 trials (276 336 patients) assessing 21 antidiabetic medications from nine drug classes were included. Subcutaneous semaglutide was the most efficacious in reducing body weight followed by oral semaglutide, exenatide twice-daily, liraglutide, and the sodium-glucose co-transporter-2 (SGLT-2) inhibitors empagliflozin, canagliflozin, dapagliflozin and ertugliflozin. The same agents also conferred the greatest reductions in systolic blood pressure. Metformin had a modest effect in reducing body weight and systolic blood pressure. Diastolic blood pressure was reduced with the SGLT-2 inhibitors pioglitazone, exenatide twice-daily and semaglutide. In subgroup analyses of trials with over 52 weeks' duration, semaglutide and SGLT-2 inhibitors reduced both body weight and systolic blood pressure. CONCLUSIONS: Semaglutide and SGLT-2 inhibitors conferred reductions both in body weight and blood pressure that were sustainable for over 1 year of treatment. These agents may be preferable treatment options for patients with type 2 diabetes who are overweight/obese and/or hypertensive.

Global mapping of overviews of systematic reviews in healthcare published between 2000 and 2020: a bibliometric analysis.

OBJECTIVE: To conduct a bibliometric analysis using a large sample of overviews of systematic reviews (OoSRs) and reveal research trends and areas of interest about these studies. STUDY DESIGN AND SETTING: We searched MEDLINE, Scopus and Cochrane Database of Systematic Reviews from 1/1/2000 to 15/10/2020. We used Scopus meta-data and two authors recorded supplementary information independently. We summarized the data using frequencies with percentages. RESULTS: A total of 1558 studies were considered eligible for analysis. We found that the publications have been increasing yearly and their nomenclature was not uniform (the most frequent label in the title was "overview of systematic reviews"). The largest number of papers and the most cited ones were published by corresponding authors from the UK. The publications were distributed across 737 scholarly journals and many of them were published in the field of complementary/alternative medicine, psychiatry/psychology, nutrition/dietetics, and pediatrics. The co-authorship analysis revealed collaborations among countries. The most common clinical conditions were depression, diabetes, cancer, dementia, pain, cardiovascular disease, stroke, obesity, and schizophrenia. CONCLUSION: OoSRs have recently become a popular approach of evidence synthesis. International collaborations between overview authors from countries with increased research productivity and countries with less research activity should be encouraged.

Methods for depicting overlap in overviews of systematic reviews: An introduction to static tabular and graphical displays.

BACKGROUND AND OBJECTIVE: To introduce potential static tabular and graphical techniques for visually presenting overlap between systematic reviews (SRs) included in overviews of systematic reviews (OoSRs). METHODS: The graphical approaches described include Venn and Euler diagrams, as well as matrix-based, node-link, and aggregation-based techniques. We used fundamental concepts of mathematics from set and network theory to develop our novel graphical approaches. The graphical displays were created using R. RESULTS: Overview authors have the flexibility to choose from a variety of visualizations, depending on the characteristics of their study. If the OoSRs include few SRs, a Venn or an Euler diagram can be used. In case of OoSRs with more SRs, Upset plots, heatmaps, and node-link graphs are more appropriate for visualizing overlapping SRs. Stacked bar plots constitute an aggregation-based technique of illustrating overlap. Strengths and limitations of each graphical approach are presented. CONCLUSION: The degree of overlap should be explored for the entire study and for specific outcomes of interest. The proposed graphical techniques may assist methodologists and authors in identifying overlap, which in turn may improve validity and transparency in OoSRs. More research is needed to understand which technique would be most useful and easiest to understand.

Glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter-2 inhibitors as combination therapy for type 2 diabetes: A systematic review and meta-analysis.

AIM: To assess the efficacy and safety of combination therapy with a glucagon-like peptide-1 receptor agonist (GLP-1 RA) and a sodium-glucose co-transporter-2 inhibitor (SGLT2i) in patients with type 2 diabetes. METHODS: We searched Medline, Embase, the Cochrane Library and grey literature sources up to 2 December 2019 for randomized controlled trials in adults with type 2 diabetes assessing the combination of GLP-1RA and SGLT2i, either as co-initiation therapy or as add-on to each other, against placebo or an active comparator. The primary outcome was change in HbA1c . Secondary outcomes included change in body weight, blood pressure and estimated glomerular filtration rate, and incidence of severe hypoglycaemia, all-cause mortality, cardiovascular mortality, myocardial infarction, stroke and hospitalization for heart failure. We pooled data using random effects meta-analyses. RESULTS: Seven trials (1913 patients) were eligible. Compared with GLP-1RA, GLP-1RA/SGLT2i combination therapy was associated with a greater reduction in HbA1c (weighted mean difference -0.61%, 95% CI -1.09% to -0.14%, four studies), body weight (-2.59 kg, -3.68 to -1.51 kg, three studies) and systolic blood pressure (-4.13 mmHg, -7.28 to -0.99 mmHg, four studies). Compared with SGLT2i, GLP-1RA/SGLT2i combination therapy reduced HbA1c (-0.85%, -1.19% to -0.52%, six studies) and systolic blood pressure (-2.66 mmHg, -5.26 to -0.06 mmHg, six studies), but not body weight (-1.46 kg, -2.94 to 0.03 kg, five studies). After excluding data for one trial that had a considerably longer duration than the remaining studies, body weight was also reduced versus SGLT2i (-1.79 kg, -2.99 to -0.59 kg, five studies). Combination therapy did not increase the incidence of severe hypoglycaemia. Data for mortality and cardiovascular outcomes were scarce. CONCLUSIONS: GLP-1RA/SGLT2i combination therapy seems to reduce HbA1c , body weight and systolic blood pressure without increasing the risk of severe hypoglycaemia compared with either GLP-1RA or SGLT2i. No conclusions can be made regarding long-term effectiveness or the effect on cardiovascular outcomes.

Efficacy and safety of statin use in children and adolescents with familial hypercholesterolaemia: a systematic review and meta-analysis of randomized-controlled trials.

PURPOSE: Statins are the mainstay of treatment for patients with familial hypercholesterolaemia (FH). However, their efficacy and safety in children and adolescents with FH has not been well-documented. The purpose of this study was to systematically investigate and meta-analyze the best available evidence from randomized-controlled trials (RCTs) regarding the efficacy and safety of statins in this population. METHODS: A comprehensive search was conducted in PubMed, Scopus and Cochrane, up to 10 January 2020. Data were expressed as mean differences with 95% confidence intervals (CI). The I2 index was employed for heterogeneity. RESULTS: Ten RCTs were included in the qualitative and quantitative analysis (1191 patients, aged 13.3 ± 2.5 years). Compared with placebo, statins led to a mean relative reduction in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglyceride and apolipoprotein B (apo-B) concentrations by -25.5% (95% CI -30.4%, -20.5%; I2 91%), -33.8% (95% CI -40.1%, -27.4%; I2 90%), -8.4% (95% CI -14.8%, -2.03%; I2 26%) and -28.8% (95% CI -33.9%, -23.6%; I2 83%), respectively. High-density lipoprotein cholesterol (HDL-C) was increased by 3.1% (95% CI 1.1%-5.2%; I2 0%). Statins were well-tolerated, with no significant differences in transaminase and creatine kinase levels or other adverse effects compared with placebo. Statins exerted no effect on growth or sexual development. CONCLUSION: Statins are quite effective in reducing TC, LDL-C, TG and apo-B and increasing HDL-C concentrations in children and adolescents with FH. No safety issues were seen with statin use.

Strategies to achieve low-density lipoprotein cholesterol targets in high-risk patients.

Several options exist in very-high risk patients who do not achieve low-density lipoprotein cholesterol (LDL-C) targets despite treatment with atorvastatin 80 mg, including switching to rosuvastatin 40 mg, adding ezetimibe or adding a proprotein convertase subtilisin/kexin type 9 inhibitor. Taking into account the safety, LDL-C lowering capacity, effect on cardiovascular events and cost of these available options, switching to rosuvastatin 40 mg appears to represent the most attractive strategy. Nevertheless, more studies are needed to confirm the effects of this strategy on LDL-C levels given the limited available data.