-
The Cochrane Database of Systematic... Nov 2023Chronic kidney disease (CKD) is a significant risk factor for cardiovascular disease (CVD) and death. Increased oxidative stress in people with CKD has been implicated... (Review)
Review
BACKGROUND
Chronic kidney disease (CKD) is a significant risk factor for cardiovascular disease (CVD) and death. Increased oxidative stress in people with CKD has been implicated as a potential causative factor. Antioxidant therapy decreases oxidative stress and may consequently reduce cardiovascular morbidity and death in people with CKD. This is an update of a Cochrane review first published in 2012.
OBJECTIVES
To examine the benefits and harms of antioxidant therapy on death and cardiovascular and kidney endpoints in adults with CKD stages 3 to 5, patients undergoing dialysis, and kidney transplant recipients.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies until 15 November 2022 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov.
SELECTION CRITERIA
We included all randomised controlled trials investigating the use of antioxidants, compared with placebo, usual or standard care, no treatment, or other antioxidants, for adults with CKD on cardiovascular and kidney endpoints.
DATA COLLECTION AND ANALYSIS
Titles and abstracts were screened independently by two authors who also performed data extraction using standardised forms. Results were pooled using random effects models and expressed as risk ratios (RR) or mean difference (MD) with 95% confidence intervals (CI). Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
MAIN RESULTS
We included 95 studies (10,468 randomised patients) that evaluated antioxidant therapy in adults with non-dialysis-dependent CKD (31 studies, 5342 patients), dialysis-dependent CKD (41 studies, 3444 patients) and kidney transplant recipients (21 studies, 1529 patients). Two studies enrolled dialysis and non-dialysis patients (153 patients). Twenty-one studies assessed the effects of vitamin antioxidants, and 74 assessed the effects of non-vitamin antioxidants. Overall, the quality of included studies was moderate to low or very low due to unclear or high risk of bias for randomisation, allocation concealment, blinding, and loss to follow-up. Compared with placebo, usual care, or no treatment, antioxidant therapy may have little or no effect on cardiovascular death (8 studies, 3813 patients: RR 0.94, 95% CI 0.64 to 1.40; I² = 33%; low certainty of evidence) and probably has little to no effect on death (any cause) (45 studies, 7530 patients: RR 0.95, 95% CI 0.82 to 1.11; I² = 0%; moderate certainty of evidence), CVD (16 studies, 4768 patients: RR 0.79, 95% CI 0.63 to 0.99; I² = 23%; moderate certainty of evidence), or loss of kidney transplant (graft loss) (11 studies, 1053 patients: RR 0.88, 95% CI 0.67 to 1.17; I² = 0%; moderate certainty of evidence). Compared with placebo, usual care, or no treatment, antioxidants had little to no effect on the slope of urinary albumin/creatinine ratio (change in UACR) (7 studies, 1286 patients: MD -0.04 mg/mmol, 95% CI -0.55 to 0.47; I² = 37%; very low certainty of evidence) but the evidence is very uncertain. Antioxidants probably reduced the progression to kidney failure (10 studies, 3201 patients: RR 0.65, 95% CI 0.41 to 1.02; I² = 41%; moderate certainty of evidence), may improve the slope of estimated glomerular filtration rate (change in eGFR) (28 studies, 4128 patients: MD 3.65 mL/min/1.73 m², 95% CI 2.81 to 4.50; I² = 99%; low certainty of evidence), but had uncertain effects on the slope of serum creatinine (change in SCr) (16 studies, 3180 patients: MD -13.35 µmol/L, 95% CI -23.49 to -3.23; I² = 98%; very low certainty of evidence). Possible safety concerns are an observed increase in the risk of infection (14 studies, 3697 patients: RR 1.30, 95% CI 1.14 to 1.50; I² = 3%; moderate certainty of evidence) and heart failure (6 studies, 3733 patients: RR 1.40, 95% CI 1.11 to 1.75; I² = 0; moderate certainty of evidence) among antioxidant users. Results of studies with a low risk of bias or longer follow-ups generally were comparable to the main analyses.
AUTHORS' CONCLUSIONS
We found no evidence that antioxidants reduced death or improved kidney transplant outcomes or proteinuria in patients with CKD. Antioxidants likely reduce cardiovascular events and progression to kidney failure and may improve kidney function. Possible concerns are an increased risk of infections and heart failure among antioxidant users. However, most studies were of suboptimal quality and had limited follow-up, and few included people undergoing dialysis or kidney transplant recipients. Furthermore, the large heterogeneity in interventions hampers drawing conclusions on the efficacy and safety of individual agents.
Topics: Adult; Humans; Kidney Failure, Chronic; Antioxidants; Renal Insufficiency, Chronic; Cardiovascular Diseases; Heart Failure
PubMed: 37916745
DOI: 10.1002/14651858.CD008176.pub3 -
International Urology and Nephrology May 2024This review aimed to assess the utility of urinary N-acetyl-β-D-glucosaminidase (uNAG) as a prognostic biomarker for nephropathy in patients with type 2 diabetes... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This review aimed to assess the utility of urinary N-acetyl-β-D-glucosaminidase (uNAG) as a prognostic biomarker for nephropathy in patients with type 2 diabetes mellitus.
METHODS
The search for relevant studies was conducted across multiple databases, including PubMed (Medline), EMBASE, LILACS, CENTRAL, IBECS, and gray literature. We employed a random effects model to calculate the standardized mean difference and 95% confidence interval. Furthermore, we assessed heterogeneity using Cochrane's Q test and Higgins' I2 statistics.
RESULTS
This review included a total of 16 articles involving 1669 patients, with 13 being case-control studies and three being cohorts. The meta-analysis conducted across all studies revealed significant heterogeneity. However, subgroup analysis of four studies indicated that an increase in uNAG among normoalbuminuric patients was associated with the development of macroalbuminuria (DMP = - 1.47; 95% CI = - 1.98 to 0.95; p < 0.00001; I = 45%). Conversely, it did not demonstrate effectiveness in predicting the development of microalbuminuria (DMP = 0.26; 95% CI = - 0.08 to 0.60; p = 0.13; I = 17%).
CONCLUSIONS
Elevated uNAG levels in normoalbuminuric patients may indicate an increased risk for the development of macroalbuminuria, but not microalbuminuria. However, the high heterogeneity observed among the studies highlights the necessity for further research to validate these findings.
Topics: Humans; Diabetic Nephropathies; Diabetes Mellitus, Type 2; Acetylglucosaminidase; Prognosis; Biomarkers; Albuminuria
PubMed: 37898960
DOI: 10.1007/s11255-023-03843-3 -
Diseases (Basel, Switzerland) Oct 2023The objective of this systematic review and meta-analysis was to assess and contrast the efficacy and safety of combining erlotinib and bevacizumab with erlotinib alone... (Review)
Review
Comparing Efficacy of Erlotinib and Bevacizumab Combination with Erlotinib Monotherapy in Patients with Advanced Non-Small Cell Lung Cancer (NSCLC): A Systematic Review and Meta-Analysis.
The objective of this systematic review and meta-analysis was to assess and contrast the efficacy and safety of combining erlotinib and bevacizumab with erlotinib alone in the treatment of patients with advanced non-small cell lung cancer (NSCLC). The authors searched databases such as PubMed, Medline, Scopus, and Cochrane Central Register of Controlled Trials for randomized control trials (RCTs) comparing erlotinib plus bevacizumab with erlotinib in NSCLC patients. The overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs) were the outcomes of interest. The pooled hazard ratio (HR) and relative risk (RR) were estimated utilizing both fixed- and random-effect models. Methodological quality of the included studies was assessed using the Cochrane Risk of Bias tool. Nine studies comprising 1698 patients with NSCLC were included in this meta-analysis, of whom 850 were treated with erlotinib plus bevacizumab, and 848 with erlotinib. The erlotinib plus bevacizumab combination significantly prolonged PFS (HR, 0.62, 95% CI: 0.56, 0.70, < 0.00001) but did not show any significant improvement in OS (HR, 0.95; 95% CI: 0.83, 1.07, = 0.39) and ORR (HR, 1.10; 95% CI: 0.98, 1.24, = 0.09). Increased risks of hypertension (RR, 5.15; 95% CI: 3.59, 7.39; < 0.00001), proteinuria (RR, 10.54; 95% CI: 3.80, 29.20; < 0.00001) and grade 3 and higher AEs (RR, 2.09; 95% CI: 1.47, 2.97; < 0.00001) were observed with the erlotinib-plus-bevacizumab combination compared to erlotinib monotherapy. On subgroup analyses, the erlotinib plus bevacizumab combination improved PFS only. Combining erlotinib and bevacizumab has been shown to improve PFS in advanced NSCLC patients but did not show any significant OS and ORR benefits. Furthermore, risks of hypertension, proteinuria, and grade 3 or higher AEs were greater with the erlotinib-and-bevacizumab combination.
PubMed: 37873790
DOI: 10.3390/diseases11040146 -
The Cochrane Database of Systematic... Oct 2023Chronic kidney disease (CKD) is a major public health problem affecting 13% of the global population. Prior research has indicated that CKD is associated with gut... (Review)
Review
BACKGROUND
Chronic kidney disease (CKD) is a major public health problem affecting 13% of the global population. Prior research has indicated that CKD is associated with gut dysbiosis. Gut dysbiosis may lead to the development and/or progression of CKD, which in turn may in turn lead to gut dysbiosis as a result of uraemic toxins, intestinal wall oedema, metabolic acidosis, prolonged intestinal transit times, polypharmacy (frequent antibiotic exposures) and dietary restrictions used to treat CKD. Interventions such as synbiotics, prebiotics, and probiotics may improve the balance of the gut flora by altering intestinal pH, improving gut microbiota balance and enhancing gut barrier function (i.e. reducing gut permeability).
OBJECTIVES
This review aimed to evaluate the benefits and harms of synbiotics, prebiotics, and probiotics for people with CKD.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies up to 9 October 2023 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) measuring and reporting the effects of synbiotics, prebiotics, or probiotics in any combination and any formulation given to people with CKD (CKD stages 1 to 5, including dialysis and kidney transplant). Two authors independently assessed the retrieved titles and abstracts and, where necessary, the full text to determine which satisfied the inclusion criteria.
DATA COLLECTION AND ANALYSIS
Data extraction was independently carried out by two authors using a standard data extraction form. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) or standardised mean difference (SMD) and 95% CI for continuous outcomes. The methodological quality of the included studies was assessed using the Cochrane risk of bias tool. Data entry was carried out by one author and cross-checked by another. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
MAIN RESULTS
Forty-five studies (2266 randomised participants) were included in this review. Study participants were adults (two studies in children) with CKD ranging from stages 1 to 5, with patients receiving and not receiving dialysis, of whom half also had diabetes and hypertension. No studies investigated the same synbiotic, prebiotic or probiotic of similar strains, doses, or frequencies. Most studies were judged to be low risk for selection bias, performance bias and reporting bias, unclear risk for detection bias and for control of confounding factors, and high risk for attrition and other biases. Compared to prebiotics, it is uncertain whether synbiotics improve estimated glomerular filtration rate (eGFR) at four weeks (1 study, 34 participants: MD -3.80 mL/min/1.73 m², 95% CI -17.98 to 10.38), indoxyl sulfate at four weeks (1 study, 42 participants: MD 128.30 ng/mL, 95% CI -242.77 to 499.37), change in gastrointestinal (GI) upset (borborymgi) at four weeks (1 study, 34 participants: RR 15.26, 95% CI 0.99 to 236.23), or change in GI upset (Gastrointestinal Symptom Rating Scale) at 12 months (1 study, 56 participants: MD 0.00, 95% CI -0.27 to 0.27), because the certainty of the evidence was very low. Compared to certain strains of prebiotics, it is uncertain whether a different strain of prebiotics improves eGFR at 12 weeks (1 study, 50 participants: MD 0.00 mL/min, 95% CI -1.73 to 1.73), indoxyl sulfate at six weeks (2 studies, 64 participants: MD -0.20 μg/mL, 95% CI -1.01 to 0.61; I² = 0%) or change in any GI upset, intolerance or microbiota composition, because the certainty of the evidence was very low. Compared to certain strains of probiotics, it is uncertain whether a different strain of probiotic improves eGFR at eight weeks (1 study, 30 participants: MD -0.64 mL/min, 95% CI -9.51 to 8.23; very low certainty evidence). Compared to placebo or no treatment, it is uncertain whether synbiotics improve eGFR at six or 12 weeks (2 studies, 98 participants: MD 1.42 mL/min, 95% CI 0.65 to 2.2) or change in any GI upset or intolerance at 12 weeks because the certainty of the evidence was very low. Compared to placebo or no treatment, it is uncertain whether prebiotics improves indoxyl sulfate at eight weeks (2 studies, 75 participants: SMD -0.14 mg/L, 95% CI -0.60 to 0.31; very low certainty evidence) or microbiota composition because the certainty of the evidence is very low. Compared to placebo or no treatment, it is uncertain whether probiotics improve eGFR at eight, 12 or 15 weeks (3 studies, 128 participants: MD 2.73 mL/min, 95% CI -2.28 to 7.75; I² = 78%), proteinuria at 12 or 24 weeks (1 study, 60 participants: MD -15.60 mg/dL, 95% CI -34.30 to 3.10), indoxyl sulfate at 12 or 24 weeks (2 studies, 83 participants: MD -4.42 mg/dL, 95% CI -9.83 to 1.35; I² = 0%), or any change in GI upset or intolerance because the certainty of the evidence was very low. Probiotics may have little or no effect on albuminuria at 12 or 24 weeks compared to placebo or no treatment (4 studies, 193 participants: MD 0.02 g/dL, 95% CI -0.08 to 0.13; I² = 0%; low certainty evidence). For all comparisons, adverse events were poorly reported and were minimal (flatulence, nausea, diarrhoea, abdominal pain) and non-serious, and withdrawals were not related to the study treatment.
AUTHORS' CONCLUSIONS
We found very few studies that adequately test biotic supplementation as alternative treatments for improving kidney function, GI symptoms, dialysis outcomes, allograft function, patient-reported outcomes, CVD, cancer, reducing uraemic toxins, and adverse effects. We are not certain whether synbiotics, prebiotics, or probiotics are more or less effective compared to one another, antibiotics, or standard care for improving patient outcomes in people with CKD. Adverse events were uncommon and mild.
Topics: Adult; Child; Humans; Synbiotics; Prebiotics; Dysbiosis; Indican; Uremic Toxins; Renal Insufficiency, Chronic; Probiotics
PubMed: 37870148
DOI: 10.1002/14651858.CD013631.pub2 -
BMJ Open Oct 2023The study intended to assess the pooled prevalence of vitamin D deficiency (VDD) and its associated factors among patients with type 2 diabetes mellitus (T2DM). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The study intended to assess the pooled prevalence of vitamin D deficiency (VDD) and its associated factors among patients with type 2 diabetes mellitus (T2DM).
DESIGN
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were employed to plan and conduct this systematic review and meta-analysis.
DATA SOURCES
PubMed, Medline, Google Scholar, Web of Science, Science Direct and the Worldwide Science database were searched from their inception to 31 January 2023.
METHODS
Data were extracted using a standardised data extraction format prepared in Microsoft Excel. The inverse variance (I) test was used to evaluate the presence of heterogeneity across the included studies. To identify the possible source of heterogeneity, subgroup analysis was carried out. Funnel plot symmetry, Begg's and Egger's tests were used to evaluate the existence of publication bias. In addition, factors associated with VDD among patients with T2DM were examined. All statistical analyses were carried out with STATA V.14 software.
RESULTS
A total of 54 studies with 38 016 study participants were included in the study. The pooled prevalence of VDD among patients with T2DM was found to be 64.2% (95% CI 60.6% to 67.8%) with a substantial level of heterogeneity (I=98.2%; p<0.001). Results of the subgroup analysis indicated that the pooled prevalence of VDD among patients with T2DM was highest (70.9%) in African nations and lowest (57.1%) in Middle East countries. Being female (pooled OR (POR) 1.60, 95% CI 1.29 to 1.97), having poor glycaemic control (POR 2.50; 95% CI 1.74 to 3.59), hypertension (POR 1.21; 95% CI 1.08 to 1.36), obesity (body mass index ≥25) (POR 1.68; 95% CI 1.16 to 2.44), dyslipidaemia (POR 2.54, 95% CI 1.37 to 4.73), albuminuria (POR 2.22, 95% CI 1.71 to 2.95), nephropathy (POR 1.58; 95% CI 1.08 to 2.31) and retinopathy (POR 1.48: 95% CI 1.17 to 1.89) were predictors of VDD among patients with T2DM.
CONCLUSIONS
More than half of patients with T2DM were suffering from VDD. Being female, having poor glycaemic control, hypertension, obesity, dyslipidaemia, albuminuria, nephropathy and retinopathy were the predictors of VDD among patients with T2DM.
Topics: Humans; Female; Male; Diabetes Mellitus, Type 2; Albuminuria; Obesity; Hypertension; Dyslipidemias; Retinal Diseases; Vitamin D Deficiency; Prevalence; Ethiopia
PubMed: 37798019
DOI: 10.1136/bmjopen-2023-075607 -
American Journal of Nephrology 2024Mineralocorticoid receptor blockade could be a potential approach for the inhibition of chronic kidney disease (CKD) progression. The benefits and harms of different... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Mineralocorticoid receptor blockade could be a potential approach for the inhibition of chronic kidney disease (CKD) progression. The benefits and harms of different mineralocorticoid receptor antagonists (MRAs) in CKD are inconsistent.
OBJECTIVES
The aim of the study was to summarize the benefits and harms of MRAs for CKD patients.
METHODS
We searched MEDLINE, EMBASE, and the Cochrane databases for trials assessing the effects of MRAs on non-dialysis-dependent CKD populations. Treatment and adverse effects were summarized using meta-analysis.
RESULTS
Fifty-three trials with 6 different MRAs involving 22,792 participants were included. Compared with the control group, MRAs reduced urinary albumin-to-creatinine ratio (weighted mean difference [WMD], -90.90 mg/g, 95% CI, -140.17 to -41.64 mg/g), 24-h urinary protein excretion (WMD, -0.20 g, 95% CI, -0.28 to -0.12 g), estimated glomerular filtration rate (eGFR) (WMD, -1.99 mL/min/1.73 m2, 95% CI, -3.28 to -0.70 mL/min/1.73 m2), chronic renal failure events (RR, 0.86, 95% CI, 0.79-0.93), and cardiovascular events (RR, 0.84, 95% CI, 0.77-0.92). MRAs increased the incidence of hyperkalemia (RR, 2.04, 95% CI, 1.73-2.40) and hypotension (RR, 1.80, 95% CI, 1.41-2.31). MRAs reduced the incidence of peripheral edema (RR, 0.65, 95% CI, 0.56-0.75) but not the risk of acute kidney injury (RR, 0.94, 95% CI, 0.79-1.13). Nonsteroidal MRAs (RR, 0.66, 95% CI, 0.57-0.75) but not steroidal MRAs (RR, 0.20, 95% CI, 0.02-1.68) significantly reduced the risk of peripheral edema. Steroidal MRAs (RR, 5.68, 95% CI, 1.26-25.67) but not nonsteroidal MRAs (RR, 0.52, 95% CI, 0.22-1.22) increased the risk of breast disorders.
CONCLUSIONS
In the CKD patients, MRAs, particularly in combination with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, reduced albuminuria/proteinuria, eGFR, and the incidence of chronic renal failure, cardiovascular and peripheral edema events, whereas increasing the incidence of hyperkalemia and hypotension, without the augment of acute kidney injury events. Nonsteroidal MRAs were superior in the reduction of more albuminuria with fewer peripheral edema events and without the augment of breast disorder events.
Topics: Humans; Mineralocorticoid Receptor Antagonists; Hyperkalemia; Albuminuria; Renal Insufficiency, Chronic; Kidney Failure, Chronic; Acute Kidney Injury; Edema; Hypotension
PubMed: 37793348
DOI: 10.1159/000534366 -
American Journal of Kidney Diseases :... Mar 2024Atrial fibrillation (AF) and chronic kidney disease (CKD) often coexist. However, it is not known whether CKD is an independent risk factor for incident AF. Therefore,... (Meta-Analysis)
Meta-Analysis
RATIONALE & OBJECTIVE
Atrial fibrillation (AF) and chronic kidney disease (CKD) often coexist. However, it is not known whether CKD is an independent risk factor for incident AF. Therefore, we evaluated the association between markers of CKD-estimated glomerular filtration rate (eGFR) and albuminuria-and incident AF.
STUDY DESIGN
Systematic review and meta-analysis of cohort studies and randomized controlled trials.
SETTING & STUDY POPULATIONS
Participants with measurement of eGFR and/or albuminuria who were not receiving dialysis.
SELECTION CRITERIA FOR STUDIES
Cohort studies and randomized controlled trials were included that reported incident AF risk in adults according to eGFR and/or albuminuria.
ANALYTICAL APPROACH
Age- or multivariate-adjusted risk ratios (RRs) for incident AF were extracted from cohort studies, and RRs for each trial were derived from event data. RRs for incident AF were pooled using random-effects models.
RESULTS
38 studies involving 28,470,249 participants with 530,041 incident AF cases were included. Adjusted risk of incident AF was greater among participants with lower eGFR than those with higher eGFR (eGFR<60 vs≥60mL/min/1.73m: RR, 1.43; 95% CI, 1.30-1.57; and eGFR<90 vs≥90mL/min/1.73m: RR, 1.42; 95% CI, 1.26-1.60). Adjusted incident AF risk was greater among participants with albuminuria (any albuminuria vs no albuminuria: RR, 1.43; 95% CI, 1.25-1.63; and moderately to severely increased albuminuria vs normal to mildly increased albuminuria: RR, 1.64; 95% CI, 1.31-2.06). Subgroup analyses showed an exposure-dependent association between CKD and incident AF, with the risk increasing progressively at lower eGFR and higher albuminuria categories.
LIMITATIONS
Lack of patient-level data, interaction between eGFR and albuminuria could not be evaluated, possible ascertainment bias due to variation in the methods of AF detection.
CONCLUSIONS
Lower eGFR and greater albuminuria were independently associated with increased risk of incident AF. CKD should be regarded as an independent risk factor for incident AF.
PLAIN-LANGUAGE SUMMARY
Irregular heartbeat, or atrial fibrillation (AF), is the commonest abnormal heart rhythm. AF occurs commonly in people with chronic kidney disease (CKD), and CKD is also common in people with AF. However, CKD in not widely recognized as a risk factor for new-onset or incident AF. In this research, we combined data on more than 28 million participants in 38 studies to determine whether CKD itself increases the chances of incident AF. We found that both commonly used markers of kidney disease (estimated glomerular filtration rate and albuminuria, ie, protein in the urine) were independently associated with a greater risk of incident AF. This finding suggests that CKD should be recognized as an independent risk factor for incident AF.
Topics: Adult; Humans; Atrial Fibrillation; Albuminuria; Renal Insufficiency, Chronic; Glomerular Filtration Rate; Risk Factors; Kidney
PubMed: 37777059
DOI: 10.1053/j.ajkd.2023.07.023 -
Ontario Health Technology Assessment... 2023Pre-eclampsia is when high blood pressure develops after 20 weeks of pregnancy and either proteinuria, maternal end-organ dysfunction, or uteroplacental dysfunction...
BACKGROUND
Pre-eclampsia is when high blood pressure develops after 20 weeks of pregnancy and either proteinuria, maternal end-organ dysfunction, or uteroplacental dysfunction causing fetal growth restriction also develops. The Fetal Medicine Foundation has created an algorithm ("the FMF algorithm") that uses maternal factors in combination with biophysical and biochemical markers to identify people at high risk for pre-eclampsia so that they can been offered acetylsalicylic acid (Aspirin) as a preventive measure. We conducted a health technology assessment to evaluate the safety, effectiveness, and cost-effectiveness of a first-trimester population-wide screening program for pre-eclampsia risk that uses the FMF algorithm ("the FMF-based screening program"). We also evaluated the accuracy of the FMF algorithm, the budget impact of publicly funding the population-wide FMF-based screening program, and patient preferences and values.
METHODS
We performed a systematic literature search of the clinical evidence. We assessed the risk of bias of each study using the Risk of Bias in Non-randomized Studies-of Interventions tool and the Quality Assessment of Diagnostic Accuracy Studies-Comparative tool, and the quality of the body of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. We performed a systematic economic literature search and conducted a cost-effectiveness analysis comparing the FMF-based screening program to standard care (screening for risk of pre-eclampsia using maternal factors alone) from a public payer perspective. We also analyzed the budget impact of publicly funding a population-wide FMF-based screening program in Ontario. We spoke with people who have experience with pregnancy and preeclampsia and their family members through direct interviews to gather preferences and values surrounding pre-eclampsia and the potential screening program.
RESULTS
We included nine studies in the clinical evidence review. The FMF-based screening program likely reduces the risk of pre-eclampsia with delivery at less than 37 weeks' gestation compared with standard care, when initiated at 11+ to 13+ weeks' gestation; risk ratios ranged from 0.64 (95% confidence interval [CI] 0.46-0.93) to 0.70 (95% CI 0.58-0.84) (GRADE: Moderate). It may reduce the risks of low birth weight (risk ratio 0.89 [95% CI 0.85-0.94]) and low Apgar score (risk ratio 0.73 [95% CI 0.63-0.85]) (GRADE: Low). Evidence on the effectiveness of the FMF-based screening program in reducing the risk of stillbirth and neonatal death was highly uncertain (GRADE: Very low). In addition, the FMF algorithm can improve the detection rate of pre-eclampsia with delivery at less than 37 weeks' gestation or at less than 34 weeks' gestation compared with conventional algorithms, although there are concerns about bias and applicability across studies. The population-wide FMF-based screening program is more effective and more costly than standard care. The incremental cost-effectiveness ratio of the population-wide FMF-based screening program compared with standard care is $3,446 per prevented case of pre-eclampsia with delivery at less than 37 weeks. The annual budget impact of publicly funding the population-wide FMF-based screening program in Ontario ranges from an additional $1.23 million in year 1 to $3.56 million in year 5, for a total of $8.50 million over the next 5 years. The population-wide FMF-based screening program was seen as valuable by those who have experienced pregnancy and their family members. Strong emphasis was placed on providing education and equitable access as part of any screening program, and participants valued the potential clinical benefits that the population-wide FMF-based screening program could provide.
CONCLUSIONS
The FMF-based screening program is likely more effective than standard care in reducing the risk of pre-eclampsia with delivery at less than 37 weeks' gestation. Also, the FMF algorithm can improve the detection rate of pre-eclampsia with delivery at less than 37 weeks' gestation or at less than 34 weeks' gestation when compared with conventional algorithms. The population-wide FMF-based screening program is more effective and more costly than standard care. We estimate that publicly funding the population-wide FMF-based screening program in Ontario would result in additional costs of $8.50 million over the next 5 years. Pregnant people and their family members valued the potential equitable access, information, and clinical benefits that the population-wide FMF-based screening program could provide.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Pre-Eclampsia; Pregnancy Trimester, First; Technology Assessment, Biomedical; Hypertension; Cost-Effectiveness Analysis
PubMed: 37772268
DOI: No ID Found -
Pediatric Nephrology (Berlin, Germany) Mar 2024Cisplatin is a chemotherapeutic drug commonly used in the treatment of many childhood solid malignancies. It is known to cause long-term nephrotoxicity, most commonly... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cisplatin is a chemotherapeutic drug commonly used in the treatment of many childhood solid malignancies. It is known to cause long-term nephrotoxicity, most commonly manifesting as reduced glomerular filtration rate and hypomagnesaemia. Existing literature regarding the epidemiology of long-term nephrotoxicity in childhood cancer describes large variation in prevalence and risk factors.
OBJECTIVES
This study is to evaluate the prevalence of, and risk factors for, long-term cisplatin nephrotoxicity after treatment for childhood cancer.
STUDY ELIGIBILITY CRITERIA
Studies were eligible for inclusion if they: (i) evaluated participants treated with cisplatin who were diagnosed with cancer < 18 years of age; (ii) investigated any author-defined measure of nephrotoxicity; and (iii) performed this evaluation 3 or more months after cisplatin cessation. Studies whose scope was broader than this were included if appropriate subgroup analysis was performed.
RESULTS
Prevalence of reduced glomerular filtration rate (GFR) ranged between 5.9 and 48.1%. Pooled prevalence of reduced GFR using studies with a modern consensus threshold of 90 ml/min/1.73 m was 29% (95% CI 0.0-58%). Prevalence of hypomagnesaemia ranged between 8.0 and 71.4%. Pooled prevalence of hypomagnesaemia was 37% (95% CI 22-51%). Substantial heterogeneity was present, with I statistics of 94% and 73% for reduced GFR and hypomagnesaemia respectively. All large, long-term follow-up studies described increased risk of reduced GFR with increasing cumulative cisplatin dose. Included studies varied as to whether cisplatin was a risk factor for proteinuria, and whether age was a risk factor for cisplatin nephrotoxicity.
LIMITATIONS
A wide range of study methodologies were noted which impeded analysis. No studies yielded data from developing health-care settings. No non-English studies were included, further limiting generalisability.
CONCLUSIONS
Both of the most common manifestations of long-term cisplatin nephrotoxicity have a prevalence of approximately a third, with increasing cumulative dose conferring increased risk of nephrotoxicity. Further work is needed to characterise the relationship between reduced GFR and hypomagnesaemia, investigate other risk factors and understand the interindividual variation in susceptibility to nephrotoxicity.
Topics: Child; Humans; Antineoplastic Agents; Cisplatin; Glomerular Filtration Rate; Magnesium; Neoplasms; Renal Insufficiency
PubMed: 37726572
DOI: 10.1007/s00467-023-06149-9 -
JAMA Sep 2023Hypertensive disorders of pregnancy are a leading cause of pregnancy-related morbidity and mortality in the US.
IMPORTANCE
Hypertensive disorders of pregnancy are a leading cause of pregnancy-related morbidity and mortality in the US.
OBJECTIVE
To conduct a targeted systematic review to update the evidence on the effectiveness of screening for hypertensive disorders of pregnancy to inform the US Preventive Services Task Force.
DATA SOURCES
MEDLINE and the Cochrane Central Register of Controlled Trials for relevant studies published between January 1, 2014, and January 4, 2022; surveillance through February 21, 2023.
STUDY SELECTION
English-language comparative effectiveness studies comparing screening strategies in pregnant or postpartum individuals.
DATA EXTRACTION AND SYNTHESIS
Two reviewers independently appraised articles and extracted relevant data from fair-or good-quality studies; no quantitative synthesis was conducted.
MAIN OUTCOMES AND MEASURES
Morbidity or mortality, measures of health-related quality of life.
RESULTS
The review included 6 fair-quality studies (5 trials and 1 nonrandomized study; N = 10 165) comparing changes in prenatal screening practices with usual care, which was routine screening at in-person office visits. No studies addressed screening for new-onset hypertensive disorders of pregnancy in the postpartum period. One trial (n = 2521) evaluated home blood pressure measurement as a supplement to usual care; 3 trials (total n = 5203) evaluated reduced prenatal visit schedules. One study (n = 2441) evaluated proteinuria screening conducted only for specific clinical indications, compared with a historical control group that received routine proteinuria screening. One additional trial (n = 80) only addressed the comparative harms of home blood pressure measurement. The studies did not report statistically significant differences in maternal and infant complications with alternate strategies compared with usual care; however, estimates were imprecise for serious, rare health outcomes. Home blood pressure measurement added to prenatal care visits was not associated with earlier diagnosis of a hypertensive disorder of pregnancy (104.3 vs 106.2 days), and incidence was not different between groups in 3 trials of reduced prenatal visit schedules. No harms of the different screening strategies were identified.
CONCLUSIONS AND RELEVANCE
This review did not identify evidence that any alternative screening strategies for hypertensive disorders of pregnancy were more effective than routine blood pressure measurement at in-person prenatal visits. Morbidity and mortality from hypertensive disorders of pregnancy can be prevented, yet American Indian/Alaska Native persons and Black persons experience inequitable rates of adverse outcomes. Further research is needed to identify screening approaches that may lead to improved disease detection and health outcomes.
Topics: Female; Humans; Infant; Pregnancy; Advisory Committees; Blood Pressure Determination; Hypertension, Pregnancy-Induced; Quality of Life; United States; Pregnancy Outcome; Black or African American; American Indian or Alaska Native
PubMed: 37721606
DOI: 10.1001/jama.2023.4934