-
The Lancet. Diabetes & Endocrinology Jan 2018There is conflicting evidence, relying on heterogeneous studies, as to whether aldosterone excess is responsible for an increased risk of cardiovascular and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There is conflicting evidence, relying on heterogeneous studies, as to whether aldosterone excess is responsible for an increased risk of cardiovascular and cerebrovascular complications in patients with primary aldosteronism. We aimed to assess the association between primary aldosteronism and adverse cardiac and cerebrovascular events, target organ damage, diabetes, and metabolic syndrome, compared with the association of essential hypertension and these cardiovascular and end organ events, by integrating results of previous studies.
METHODS
We did a meta-analysis of prospective and retrospective observational studies that compared patients with primary aldosteronism and essential hypertension, to analyse the association between primary aldosteronism and stroke, coronary artery disease (as co-primary endpoints), atrial fibrillation and heart failure, target organ damage, metabolic syndrome, and diabetes (as secondary endpoints). We searched MEDLINE and Cochrane Library for articles published up to Feb 28, 2017, with no start date restriction. Eligible studies compared patients with primary aldosteronism with patients with essential hypertension (as a control group) and reported on the clinical events or endpoints of interest. We also compared primary aldosteronism subtypes, aldosterone-producing adenoma, and bilateral adrenal hyperplasia.
FINDINGS
We identified 31 studies including 3838 patients with primary aldosteronism and 9284 patients with essential hypertension. After a median of 8·8 years (IQR 6·2-10·7) from the diagnosis of hypertension, compared with patients with essential hypertension, patients with primary aldosteronism had an increased risk of stroke (odds ratio [OR] 2·58, 95% CI 1·93-3·45), coronary artery disease (1·77, 1·10-2·83), atrial fibrillation (3·52, 2·06-5·99), and heart failure (2·05, 1·11-3·78). These results were consistent for patients with aldosterone-producing adenoma and bilateral adrenal hyperplasia, with no difference between these subgroups. Similarly, primary aldosteronism increased the risk of diabetes (OR 1·33, 95% CI 1·01-1·74), metabolic syndrome (1·53, 1·22-1·91), and left ventricular hypertrophy (2·29, 1·65-3·17).
INTERPRETATION
Diagnosing primary aldosteronism in the early stages of disease, with early initiation of specific treatment, is important because affected patients display an increased cardiovascular risk compared with patients with essential hypertension.
FUNDING
None.
Topics: Cardiovascular Diseases; Essential Hypertension; Humans; Hyperaldosteronism; Prognosis; Prospective Studies; Retrospective Studies
PubMed: 29129575
DOI: 10.1016/S2213-8587(17)30319-4 -
BMC Neurology Mar 2014There are a number of instruments that describe severity and progression of multiple sclerosis and they are increasingly used as endpoints to assess the effectiveness of... (Review)
Review
Systematic literature review and validity evaluation of the Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Functional Composite (MSFC) in patients with multiple sclerosis.
BACKGROUND
There are a number of instruments that describe severity and progression of multiple sclerosis and they are increasingly used as endpoints to assess the effectiveness of therapeutic interventions. We examined to what extent the psychometric properties of two accepted instruments--EDSS and MSFC--meet methodological standards and the value they have in clinical trials.
METHODS
We conducted a systematic literature search in relevant databases [MEDLINE (PubMed), ISI Web of Science, EMBASE, PsycINFO & PSYNDEX, CINAHL] yielding 3,860 results. Relevant full-text publications were identified using abstract and then full-text reviews, and the literature was reviewed.
RESULTS
For evaluation of psychometric properties (validity, reliability, sensitivity of change) of EDSS and MSFC, 120 relevant full-text publications were identified, 54 of them assessed the EDSS, 26 the MSFC and 40 included both instruments. The EDSS has some documented weaknesses in reliability and sensitivity to change. The main limitations of the MSFC are learning effects and the z-scores method used to calculate the total score. However, the methodological criterion of validity applies sufficiently for both instruments.For use in clinical studies, we found the EDSS to be preferred as a primary and secondary outcome measure in recent studies (50 EDSS, 9 MSFC).
CONCLUSIONS
Recognizing their strengths and weaknesses, both EDSS and MSFC are suitable to detect the effectiveness of clinical interventions and to monitor disease progression. Almost all publications identify the EDSS as the most widely used tool to measure disease outcomes in clinical trials. Despite some limitations, both instruments are accepted as endpoints and neither are discussed as surrogate parameters in identified publications. A great advantage of the EDSS is its international acceptance (e.g. by EMA) as a primary endpoint in clinical trials and its broad use in trials, enabling cross-study comparisons.
Topics: Clinical Trials as Topic; Disability Evaluation; Humans; Multiple Sclerosis; Psychometrics
PubMed: 24666846
DOI: 10.1186/1471-2377-14-58 -
The Journal of Headache and Pain Sep 2023Intranasal agents may be ideal for the treatment of migraine patients. Many new acute intranasal-specific therapies have been developed, but few of them have been... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Intranasal agents may be ideal for the treatment of migraine patients. Many new acute intranasal-specific therapies have been developed, but few of them have been directly compared. The aim of this network meta-analysis (NMA) was to compare the efficacy and safety of various intranasal agents for the treatment of acute migraine in adult patients.
METHODS
The Cochrane Register of Controlled Trials, Embase, and PubMed were searched from inception to 15 August 2023. Randomized controlled trials (RCTs) using intranasal agents (no restrictions on dose, formulation, dosing regimen or timing of the first dose) to treat adult patients with acute migraine were included. The primary efficacy endpoint was pain freedom at 2 h, and the primary safety endpoint was adverse events (AEs). The analysis process followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
RESULTS
Nineteen studies (21 RCTs, 9738 participants) were included. Compared to the placebo, 5 mg of zolmitriptan using a conventional liquid nasal spray device was the most effective for pain freedom at 2 h [odds ratio (OR): 4.67, 95% confidence interval (CI): 3.43 to 6.43] and 24 h (OR: 5.49, 95% CI: 3.58 to 8.42) among all the interventions. Butorphanol nasal spray 1 mg was the most effective (OR: 8.62, 95% CI: 1.11 to 66.92) for pain freedom at 1 h, but with low-quality evidence. DFN-02 presented the highest freedom from nausea (OR: 4.95, 95% CI: 1.29 to 19.01) and phonophobia (OR: 5.36, 95% CI: 1.67 to 17.22) at 2 h, albeit with lower odds of achieving complete pain freedom. ROX-828 showed the highest improvement in freedom from photophobia at 2 h (OR: 4.03, 95% CI: 1.66 to 9.81). Dihydroergotamine nasal spray was significantly associated with the highest risk of AEs (OR: 9.65, 95% CI: 4.39 to 21.22) and was not recommended for routine use. Zavegepant nasal spray demonstrated the lowest risk of AEs (OR: 2.04, 95% CI: 1.37 to 3.03). The results of sensitivity analyses for the primary endpoints (pain freedom at 2 h and AEs) were generally consistent with those of the base case model.
CONCLUSIONS
Compared with other new intranasal-specific therapies in treating migraine attacks, zolmitriptan nasal spray 5 mg was the most effective agent for pain freedom at 2 h. Zavegepant nasal spray 10 mg had the fewest adverse side effects.
Topics: Adult; Humans; Nasal Sprays; Network Meta-Analysis; Migraine Disorders; Oxazolidinones
PubMed: 37723470
DOI: 10.1186/s10194-023-01662-6 -
Orthopaedic Journal of Sports Medicine Jun 2023Patellar tendinopathy (PT) mainly affects athletes who use the tendon for repeated energy storage and release activities. It can have a striking impact on athletes'...
BACKGROUND
Patellar tendinopathy (PT) mainly affects athletes who use the tendon for repeated energy storage and release activities. It can have a striking impact on athletes' careers, although data on its real prevalence and incidence are sparse. Research efforts should start from the results of reliable and updated epidemiological research to help better understand the impact of PT and underpin preventative measures.
PURPOSE
To determine the prevalence and incidence of PT in athletes and the general population.
DESIGN
Systematic review; Level of evidence, 3.
METHODS
A systematic review of the literature was performed on January 17, 2022, and conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The PubMed, Web of Science, and Wiley Cochrane Library databases were searched for epidemiological reports of any evidence level and clinical studies reporting data on the incidence or prevalence of PT for the 11,488 retrieved records. The primary endpoint was the prevalence and incidence of PT in sport-active patients. The secondary endpoints were PT prevalence and incidence in subgroups of athletes based on sex, age, sport type, and sport level played, as well as the same epidemiological measures in the general population.
RESULTS
A total of 28 studies, with 28,171 participants, were selected and used for the qualitative and quantitative analysis. The general and athletes' populations reported an overall PT prevalence of 0.1% and 18.3%, respectively. In athletes, the prevalence of PT was 11.2% in women and 17% in men ( = .070). The prevalence of PT in athletes <18 years was 10.1%, while it was 21.3% in athletes ≥18 years ( = .004). The prevalence of PT was 6.1% in soccer players, 20.8% in basketball players, and 24.8% in volleyball players. Heterogeneous PT diagnostic approaches were observed. Higher prevalence values were found when PT diagnoses were made using patient-reported outcomes versus clinical evaluations ( = .004).
CONCLUSION
This review demonstrated that PT is a common problem in the male and female sport-active populations. There are twice as many athletes aged ≥18 years than there are <18 years. Volleyball and basketball players are most affected by PT.
PubMed: 37347023
DOI: 10.1177/23259671231173659 -
Cancer Treatment Reviews Mar 2022Circulating tumor DNA (ctDNA) is increasingly being used as a biomarker in early breast cancer (EBC). We performed a systematic review and meta-analysis to investigate... (Meta-Analysis)
Meta-Analysis Review
Circulating tumor DNA (ctDNA) is increasingly being used as a biomarker in early breast cancer (EBC). We performed a systematic review and meta-analysis to investigate the prognostic value of ctDNA in patients with EBC treated with neoadjuvant therapy (NAT). We searched Medline, Web of Science and Embase for observational or interventional studies that included patients with EBC undergoing NAT, reported outcomes related to the predefined endpoints, and had full text articles available. Study selection followed the PRISMA guidelines and quality assessment the REMARK tool for biomarker studies. Primary endpoint was impact of ctDNA detection in different time points (baseline, on-treatment, and after NAT) on relapse-free survival (RFS) and overall survival (OS). Secondary endpoints included the association of ctDNA detection with pathologic complete response (pCR), and the positive and negative predictive value of ctDNA detection in predicting residual disease after NAT. From the 2908 studies initially identified, 11 met the eligibility criteria and were included in the meta-analysis. Detection of ctDNA, both at baseline and after completion of NAT, significantly associated to worse RFS (HR 4.22, 95% CI: 1.29-13.82 and HR 5.67, 95% CI: 2.73-11.75, respectively) and worse OS (HR 19.1, 95% CI: 6.9-53.04 and HR 4.00, 95% CI: 1.90-8.42, respectively). In contrast, detection of ctDNA did not associate with the probability of achieving a pCR. Our results suggest that ctDNA assessment during NAT for EBC merits further evaluation as a stratification risk factor in prospective trials, in order to better individualize patient's treatment.
Topics: Breast Neoplasms; Circulating Tumor DNA; Female; Humans; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Prognosis; Prospective Studies
PubMed: 35219090
DOI: 10.1016/j.ctrv.2022.102362 -
Reviews in Cardiovascular Medicine Dec 2021Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is used as mechanical circulatory support in cardiogenic shock (CS). It restores peripheral perfusion, at the... (Meta-Analysis)
Meta-Analysis
Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is used as mechanical circulatory support in cardiogenic shock (CS). It restores peripheral perfusion, at the expense of increased left ventricle (LV) afterload. In this setting, Impella can be used as direct unloading strategy. Aim of this meta-analysis was to investigate efficacy and safety of LV unloading with Impella during ECMO in CS. A systematic search on Medline, Scopus and Cochrane Library was performed using as combination of keywords: extracorporeal membrane oxygenation, Impella, percutaneous micro axial pump, ECPELLA, cardiogenic shock. We aimed to include studies, which compared the use of ECMO with and without Impella (ECPELLA vs. ECMO). Primary endpoint was short-term all-cause mortality; secondary endpoints included major bleeding, haemolysis, need for renal replacement therapy (RRT) and cerebrovascular accident (CVA). Five studies met the inclusion criteria, with a total population of 972 patients. The ECPELLA cohort showed improved survival compared to the control group (RR (Risk Ratio): 0.86; 95% CI (Confidence Interval): 0.76, 0.96; = 0.009). When including in the analysis only studies with homogeneous comparator groups, LV unloading with Impella remained associated with significant reduction in mortality (RR: 0.85; 95% CI: 0.75, 0.97; = 0.01). Haemolysis (RR: 1.70; 95% CI: 1.35, 2.15; < 0.00001) and RRT (RR: 1.86; 95% CI: 1.07, 3.21; = 0.03) occurred at a higher rate in the ECPELLA group. There was no difference between the two groups in terms of major bleeding (RR: 1.37; 95% CI: 0.88, 2.13; = 0.16) and CVA (RR: 0.91; 95% CI: 0.61, 1.38; = 0.66). In conclusion, LV unloading with Impella during ECMO was associated with improved survival, despite increased haemolysis and need for RRT, without additional risk of major bleeding and CVA.
Topics: Extracorporeal Membrane Oxygenation; Heart Ventricles; Heart-Assist Devices; Humans; Shock, Cardiogenic; Stroke
PubMed: 34957789
DOI: 10.31083/j.rcm2204154 -
Dermatology and Therapy May 2022The comparative efficacy of targeted systemic therapies for moderate to severe atopic dermatitis (AD) has not been systematically assessed using recent phase 3 data....
INTRODUCTION
The comparative efficacy of targeted systemic therapies for moderate to severe atopic dermatitis (AD) has not been systematically assessed using recent phase 3 data. This network meta-analysis assesses the comparative efficacy of targeted systemic therapies without the addition of topical corticosteroids (TCS) and/or topical calcineurin inhibitors (TCI) in adults with moderate to severe AD.
METHODS
The systematic literature review searched through 17 May 2021 for phase 3/4 trials with upadacitinib, interleukin-4 (IL-4), interleukin-13 (IL-13), or JAK inhibitors compared with placebo or active intervention for adults and adolescents with moderate to severe AD with inadequate response to TCS/TCI or for whom TCS/TCI was medically inadvisable, without restrictions on year or region. Researchers assessed data using PRISMA guidelines. The proportion of patients achieving trial co-primary endpoints [Investigator Global Assessment (IGA) score of 0 or 1 (clear or almost clear) and reduction of ≥ 2 points from baseline; proportion of patients achieving Eczema Area and Severity Index (EASI) improvement ≥ 75% from baseline (EASI-75)]; EASI improvement ≥ 90% from baseline (EASI-90); and ≥ 4-point improvement on Pruritus Numerical Rating Scale from baseline (ΔNRS ≥ 4) were evaluated using Bayesian network meta-analysis.
RESULTS
Of 3415 initially identified records, network meta-analysis (NMA) ultimately included 6 records representing 9 unique studies. Two upadacitinib trials were also included. Eleven clinical trials including 6254 patients were analyzed. Upadacitinib 30 mg daily was the most efficacious therapy across all endpoints at the primary endpoint (week 12 or 16) and at earlier timepoints, followed by upadacitinib 15 mg daily and abrocitinib 200 mg daily.
DISCUSSION
Many factors need to be considered for treatment selection for AD. These findings can help healthcare providers when personalizing a patient's treatment.
CONCLUSION
Upadacitinib 30 mg daily, upadacitinib 15 mg daily, and abrocitinib 200 mg daily may be the most efficacious targeted systemic therapies over 12-16 weeks of therapy in AD.
PubMed: 35435637
DOI: 10.1007/s13555-022-00721-1 -
International Journal of Colorectal... Oct 2021Over the last years, laparoscopic appendectomy has progressively replaced open appendectomy and become the current gold standard treatment for suspected, uncomplicated...
BACKGROUND
Over the last years, laparoscopic appendectomy has progressively replaced open appendectomy and become the current gold standard treatment for suspected, uncomplicated appendicitis. At the same time, though, it is an ongoing discussion that antibiotic therapy can be an equivalent treatment for patients with uncomplicated appendicitis. The aim of this systematic review was to determine the safety and efficacy of antibiotic therapy and compare it to the laparoscopic appendectomy for acute, uncomplicated appendicitis.
METHODS
The PubMed database, Embase database, and Cochrane library were scanned for studies comparing laparoscopic appendectomy with antibiotic treatment. Two independent reviewers performed the study selection and data extraction. The primary endpoint was defined as successful treatment of appendicitis. Secondary endpoints were pain intensity, duration of hospitalization, absence from work, and incidence of complications.
RESULTS
No studies were found that exclusively compared laparoscopic appendectomy with antibiotic treatment for acute, uncomplicated appendicitis.
CONCLUSIONS
To date, there are no studies comparing antibiotic treatment to laparoscopic appendectomy for patients with acute uncomplicated appendicitis, thus emphasizing the lack of evidence and need for further investigation.
Topics: Acute Disease; Anti-Bacterial Agents; Appendectomy; Appendicitis; Humans; Laparoscopy; Length of Stay; Treatment Outcome
PubMed: 33852068
DOI: 10.1007/s00384-021-03927-5 -
Digestive Diseases and Sciences Jun 2023We conducted a systematic literature review to understand the evidence supporting treatment decisions for cholestatic pruritus associated with primary biliary...
BACKGROUND AND AIMS
We conducted a systematic literature review to understand the evidence supporting treatment decisions for cholestatic pruritus associated with primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC).
METHODS
Studies that enrolled ≥ 75% participants with PBC or PSC and reported ≥ 1 endpoint(s) related to efficacy, safety, health-related quality of life (HRQoL) or other patient-reported outcomes were included. Bias was assessed using the Cochrane risk of bias tool for randomised controlled trials (RCTs) and the Quality of Cohort studies tool for non-RCTs.
RESULTS
Thirty-nine publications were identified, covering 42 studies and six treatment classes (including investigational and approved products): anion-exchange resins, antibiotics (rifampicin/derivatives), opiates, selective serotonin reuptake inhibitors, fibrates, ileal bile acid transporter inhibitors and other agents not categorised in these six classes. Across studies, median sample size was small (n = 18), 20 studies were over 20 years old, 25 followed patients for ≤ 6 weeks, only 25 were RCTs. Pruritus was assessed using several different tools, with inconsistencies in their application. Cholestyramine, considered first-line therapy for moderate-severe cholestatic pruritus, was assessed in six studies (two RCTs) including 56 patients with PBC and 2 with PSC, with evidence of efficacy demonstrated in only three studies, among which, two RCTs were assessed as having a high risk of bias. Findings were similar for other drug classes.
CONCLUSIONS
There is a lack of consistent and reproducible evidence available on efficacy, impact on HRQoL, and safety of cholestatic pruritus treatments, leaving physicians to rely on clinical experience rather than evidence-based medicine for treatment selection.
Topics: Humans; Young Adult; Adult; Liver Cirrhosis, Biliary; Cholangitis, Sclerosing; Pruritus; Fibric Acids; Quality of Life
PubMed: 36933112
DOI: 10.1007/s10620-023-07862-z -
Nutrition, Metabolism, and... Jun 2021Aim of the present meta-analysis and network metanalysis (NMA) is the assessment of the effects of physical exercise on glucose control and cardiovascular risk factors... (Meta-Analysis)
Meta-Analysis
Comparison between different types of exercise training in patients with type 2 diabetes mellitus: A systematic review and network metanalysis of randomized controlled trials.
AIM
Aim of the present meta-analysis and network metanalysis (NMA) is the assessment of the effects of physical exercise on glucose control and cardiovascular risk factors in type 2 diabetes.
DATA SYNTHESIS
This metanalysis includes all available trials exploring the effects of different exercise modalities in type 2 diabetes, with a duration of ≥3 months. The standardized difference in means (SDM) with 95% Confidence Intervals were calculated. Data were analyzed using MetaXL and Rev Man 5.0. Primary endpoint was the effect of exercise versus no exercise on HbA1c and fasting plasma glucose (FPG) at endpoint. Secondary endpoints were body weight and fat, waist circumference, and blood pressure. A comparison of different exercise training modalities (aerobic, resistance and combined) for the same endpoints was also performed, choosing 'no exercise' as the reference for indirect comparisons. We included 25 trials fulfilling all inclusion criteria. Physical exercise versus no exercise produced a small, but significant, improvement of HbA1c, body fat, and systolic blood pressure at endpoint (-0.3 [-0.1;-0.4]%, -1.44 [-2.22, -0.66]%, and -5.6 [-9.5, -1.6] mmHg, respectively). Combined, supervised aerobic and resistance exercise were associated with a significantly greater reduction of HbA1c (SDM, -0.4 [-0.6;-0.3], -0.2 [-0.4;-0.1], and -0.2 [-0.3;-0.1]%, respectively), but not of FPG, in comparison with no exercise.
CONCLUSIONS
Physical exercise produces small, but detectable, advantages on glycemic control and cardiovascular risk factors and should be suggested in type 2 diabetes. Combined aerobic/resistance training seems to be superior to aerobic training alone, but differences are small and the reliability of supporting evidence limited.
Topics: Biomarkers; Blood Glucose; Diabetes Mellitus, Type 2; Exercise Therapy; Female; Glycated Hemoglobin; Glycemic Control; Humans; Male; Middle Aged; Network Meta-Analysis; Randomized Controlled Trials as Topic; Resistance Training; Treatment Outcome
PubMed: 33965297
DOI: 10.1016/j.numecd.2021.02.030