Summary Risk Ratios Research Articles

Causal risk factors for asthma in Mendelian randomization studies: A systematic review and meta-analysis.

Several risk factors for asthma have been proposed; however, the causality of these associations is sometimes unclear. Mendelian randomization is a powerful epidemiological approach that can help elucidate the causality of risk factors. The aim of the present study was to identify causal risk factors for asthma through Mendelian Randomization studies. A systematic search of PubMed and EMBASE was conducted, to identify studies investigating risk factors for asthma or respiratory allergies through Mendelian Randomization. When two or more studies investigated the same risk factor a meta-analysis was conducted. Of 239 studies initially identified, 41 were included. A causal association between adiposity and adult asthma risk was found in 10 out of 12 studies with a summary risk ratio of 1.05 per kg/m2 increase in BMI (95% CI: 1.03-1.07). Puberty timing (n=3), alcohol (n=2), and linoleic acid (n=1) had causal effects on asthma risk, while vitamins/minerals (n=6) showed no consistent effect on asthma. The effect of smoking on adult asthma conflicted between studies. Several of the significant associations of asthma with immune related proteins (n=5) and depression (n=2) investigated through multiple traits analyses could generally benefit from replications in independent datasets. This systematic review and meta-analysis found evidence for causal effects of adiposity, puberty timing, linoleic acid, alcohol, immune related proteins, and depression on risk of asthma.

Estimating risk and rate ratio in rare events meta-analysis with the Mantel-Haenszel estimator and assessing heterogeneity.

Meta-analysis of binary outcome data faces often a situation where studies with a rare event are part of the set of studies to be considered. These studies have low occurrence of event counts to the extreme that no events occur in one or both groups to be compared. This raises issues how to estimate validly the summary risk or rate ratio across studies. A preferred choice is the Mantel-Haenszel estimator, which is still defined in the situation of zero studies unless all studies have zeros in one of the groups to be compared. For this situation, a modified Mantel-Haenszel estimator is suggested and shown to perform well by means of simulation work. Also, confidence interval estimation is discussed and evaluated in a simulation study. In a second part, heterogeneity of relative risk across studies is investigated with a new chi-square type statistic which is based on a conditional binomial distribution where the conditioning is on the event margin for each study. This is necessary as the conventional Q-statistic is undefined in the occurrence of zero studies. The null-distribution of the proposed Q-statistic is obtained by means of a parametric bootstrap as a chi-square approximation is not valid for rare events meta-analysis, as bootstrapping of the null-distribution shows. In addition, for the effect heterogeneity situation, confidence interval estimation is considered using a nonparametric bootstrap procedure. The proposed techniques are illustrated at hand of three meta-analytic data sets.

EXPLORING THE ROLE OF ADJUNCT CORTICOSTEROID THERAPY TO DECREASE COMMUNITY-ACQUIRED PNEUMONIA-RELATED COMPLICATIONS: A SYSTEMATIC REVIEW AND META-ANALYSIS

SESSION TITLE: Outcomes in Pneumonia and NTMSESSION TYPE: Rapid Fire Original InvPRESENTED ON: 10/17/2022 12:15 pm - 1:15 pmPURPOSE: Adjunct corticosteroid therapy to patients with community-acquired pneumonia (CAP) remains controversial in clinical practice. We performed an updated systematic review and meta-analysis to assess the efficacy of corticosteroids in decreasing complications of CAP such as ARDS, empyema, shock, and pleural effusion.METHODS: We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Scopus for randomized controlled trials (RCT) from each database’s inception to February 2022. We estimated the summary risk ratios (RR) with their corresponding 95% confidence interval (CI) through random effects Mental-Haenszel model. Subgroup analyses were also conducted. I-squared statistics (I2) were used to evaluate heterogeneity. Publication bias was assessed with Begg’s tests.RESULTS: We included 11 RCTs containing 3,509 patients with CAP. Adjunctive corticosteroid therapy was associated with significant reduction in CAP-related complications (RR = 0.73, CI 0.55 – 0.97, p = 0.015, I2 = 56.9%). In subgroup analysis, patients who received higher dose of steroids (> 50 mg prednisone equivalents/day) had a more significant reduction in CAP-related complications (RR = 0.46, CI = 0.31 – 0.68, p = 0.001, I2 = 12.2%). No significant publication bias was observed with Begg’s test (p = 0.087).CONCLUSIONS: This meta-analysis indicates that adjunctive corticosteroids significantly reduce CAP-related complications.CLINICAL IMPLICATIONS: Adjunctive corticosteroid therapy is a plausible option to limit complications such as ARDS, empyema, shock, and pleural effusion in CAP patients with co-morbidities and who are at high risk for clinical deterioration.DISCLOSURES: No relevant relationships by Mubashir Ayaz AhmedNo relevant relationships by Shayet Hossain EshanNo relevant relationships by Sami HusseinNo relevant relationships by Mohammed HusseinNo relevant relationships by Jose Medina InojosaNo relevant relationships by Wasey Ali Yadullahi MirNo relevant relationships by Sudha MisraNo relevant relationships by Kamalnath Sankaran RajagopalanNo relevant relationships by Chenyu Sun SESSION TITLE: Outcomes in Pneumonia and NTM SESSION TYPE: Rapid Fire Original Inv PRESENTED ON: 10/17/2022 12:15 pm - 1:15 pm PURPOSE: Adjunct corticosteroid therapy to patients with community-acquired pneumonia (CAP) remains controversial in clinical practice. We performed an updated systematic review and meta-analysis to assess the efficacy of corticosteroids in decreasing complications of CAP such as ARDS, empyema, shock, and pleural effusion. METHODS: We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Scopus for randomized controlled trials (RCT) from each database’s inception to February 2022. We estimated the summary risk ratios (RR) with their corresponding 95% confidence interval (CI) through random effects Mental-Haenszel model. Subgroup analyses were also conducted. I-squared statistics (I2) were used to evaluate heterogeneity. Publication bias was assessed with Begg’s tests. RESULTS: We included 11 RCTs containing 3,509 patients with CAP. Adjunctive corticosteroid therapy was associated with significant reduction in CAP-related complications (RR = 0.73, CI 0.55 – 0.97, p = 0.015, I2 = 56.9%). In subgroup analysis, patients who received higher dose of steroids (> 50 mg prednisone equivalents/day) had a more significant reduction in CAP-related complications (RR = 0.46, CI = 0.31 – 0.68, p = 0.001, I2 = 12.2%). No significant publication bias was observed with Begg’s test (p = 0.087). CONCLUSIONS: This meta-analysis indicates that adjunctive corticosteroids significantly reduce CAP-related complications. CLINICAL IMPLICATIONS: Adjunctive corticosteroid therapy is a plausible option to limit complications such as ARDS, empyema, shock, and pleural effusion in CAP patients with co-morbidities and who are at high risk for clinical deterioration. DISCLOSURES: No relevant relationships by Mubashir Ayaz Ahmed No relevant relationships by Shayet Hossain Eshan No relevant relationships by Sami Hussein No relevant relationships by Mohammed Hussein No relevant relationships by Jose Medina Inojosa No relevant relationships by Wasey Ali Yadullahi Mir No relevant relationships by Sudha Misra No relevant relationships by Kamalnath Sankaran Rajagopalan No relevant relationships by Chenyu Sun

Duloxetine for prevention and treatment of chemotherapy-induced peripheral neuropathy (CIPN): systematic review and meta-analysis

IntroductionDuloxetine has previously been reported to be promising in the setting of chemotherapy-induced peripheral neuropathy (CIPN). The aim of this study was to conduct a comprehensive systematic review and meta-analysis,...

Relations between the Consumption of Fatty or Lean Fish and Risk of Cardiovascular Disease and All-Cause Mortality: A Systematic Review and Meta-Analysis

Fish consumption is associated with a reduced risk of cardiovascular diseases (CVDs) partly ascribed to the high content of long-chain (LC) n-3 PUFAs; however, not all fish types are equally rich in these components. To date, it is not clear whether the beneficial effects of fish consumption are shared by fatty and lean fish. Therefore, the aim of this meta-analysis was to synthesize knowledge regarding the relation between the intake of fatty fish or lean fish and the risk of cardiovascular events and all-cause mortality. We conducted a systematic search in PubMed, Web of Science, and Embase until May 2021 for full text with a prospective design involving humans providing data for the highest compared with the lowest fish consumption categories. Summary risk ratios (RRs) and 95% CIs were estimated using a random-effects model. Out of 1902 articles retrieved from the literature search, 19 reports met the criteria for inclusion in the meta-analysis. Altogether, studies on fatty fish comprised 1,320,596 person-years of follow-up, 20,531 incident coronary heart disease (CHD) cases, 9256 incident CVD cases, and 104,763 total deaths. Studies on lean fish comprised 937,362 person-years of follow-up, 21,636 incident CHD cases, 7315 incident CVD cases, and 16,831 total deaths. An inverse association was present for fatty fish with CHD incidence (RR: 0.92; 95% CI: 0.86, 0.97), CHD mortality (RR: 0.83; 95% CI: 0.70, 0.98), and total mortality (RR: 0.97; 95% CI: 0.94, 0.99). This was not the case for lean fish. The summary estimates for CVD incidence and mortality did not show significant association with both fatty fish and lean fish consumption. The study findings are innovative in highlighting that the health benefits so far linked to fish consumption are, in fact, driven by fatty fish.

Side effects and treatment initiation barriers of sodium-glucose cotransporter 2 inhibitors in heart failure: a systematic review and meta-analysis.

Physicians are sometimes reluctant to initiate guideline-directed therapy in patients with heart failure and reduced ejection fraction (HFrEF) due to concerns of adverse events. We explored the risk of hypotension, volume depletion, and acute kidney injury (AKI) on sodium-glucose cotransporter 2 (SGLT2) inhibitors in HFrEF populations. We determined summary risk ratios (RRs) by conducting a meta-analysis on reported aforementioned adverse events on SGLT2 inhibitors from randomized controlled trials. We explored robustness of meta-analyses by computing fragility and/or reverse fragility index (FI or RFI) and its corresponding fragility quotient (FQ or RFQ) for each outcome. A total of 10 050 patients with HFrEF entered the final meta-analysis. Hypotension was reported in 4.5% (219/4836) on SGLT2 inhibitors and in 4.1% (202/4846) on placebo (RR 1.09, 95% confidence interval [CI] 0.91-1.31, p = 0.36). An RFI of 21 and RFQ of 0.002 suggest robust findings for hypotension. Volume depletion occurred in 9.4% (473/5019) on SGLT2 inhibitors and in 8.7% (438/5031) on placebo (RR 1.07, 95% CI 0.95-1.21, p = 0.25), respectively. RFI of 19 and RFQ of 0.001 suggest moderately robust findings for volume depletion. AKI was reported in fewer patients (1.9% [95/4888]) on SGLT2 inhibitors than on placebo (2.8% [140/4899]) providing lower incidence of AKI (RR 0.69, 95% CI 0.51-0.93, p = 0.02). FI of 14 and RFQ of 0.001 suggest moderately robust findings for AKI. Sodium-glucose cotransporter 2 inhibitor therapy is not associated with a clinically relevant risk of hypotension and volume depletion. Its use reduces the risk of AKI. This analysis supports current guideline recommendations on early use of SGLT2 inhibitors.

Association of Dietary Intake and Biomarker of α-Linolenic Acid With Incident Colorectal Cancer: A Dose-Response Meta-Analysis of Prospective Cohort Studies.

Background and ObjectiveThere is keen interest in better understanding the impacts of alpha-linolenic acid (ALA), a plant-derived n-3 fatty acid, in ameliorating the development of cancer; however, results of several prospective cohorts present an inconsistent association between ALA intake and the incident colorectal cancer (CRC). We aimed to investigate the summary association of dietary intake and biomarkers of ALA with CRC risk based on the prospective cohorts.MethodsPertinent prospective cohorts were identified in Cochrane Library, PubMed, and EMBASE from inception to February 2022. Study-specific risk ratios (RRs) with 95% confidence intervals (CIs) for comparing the top with the bottom quartiles of ALA levels were combined using a random-effects model. Nonlinear dose-response relationships of ALA levels in diet and blood with CRC risk were assessed using the restricted cubic spline models, respectively.ResultsOver the duration of follow-up with a median of 9.3 years ranging from 1 to 28 years, 12,239 CRC cases occurred among 861,725 participants from 15 cohorts (11 studies on diet and 5 studies on biomarkers including 4 on blood and 1 on adipose tissue). The summary RR was 1.03 (95% CI: 0.97, 1.10; I2: 0.00%) for dietary intake and 0.83 (95% CI: 0.69, 0.99; I2: 0.00%) for biomarker. Each 0.1% increase in the levels of ALA in blood was associated with a 10% reduction in risk of CRC (summary RR: 0.90, 95% CI: 0.80, 0.99; I2: 38.60%), whereas no significant dose-response association was found between dietary intake of ALA and the incident CRC (p for non-linearity = 0.18; p for linearity = 0.24).ConclusionsBlood levels of ALA were inversely and linearly associated with the risk of CRC, which suggested that increased intake of ALA to improve circulating levels was beneficial for CRC prevention.

State care in childhood and adult mortality: a systematic review and meta-analysis of prospective cohort studies

BackgroundRemoval from family of origin to state care can be a highly challenging childhood experience and is itself linked to an array of unfavourable outcomes in adult life. We aim to synthetise evidence on the risk of adult mortality in people with a history of state care in early life, and assess the association according to different contexts.MethodsIn this systematic review and meta-analysis, we focused on four health outcomes hypothesised to be associated with exposure to early state care: total mortality, cardiovascular disease, cancer, and suicide. We searched the electronic databases PubMed and Embase from inception to Jan 21, 2022, for studies fulfilling the following criteria: it was a prospective study in which the assessment of care was made up to 18 years of age; it included an unexposed comparator group; the focus of the study was temporary out-of-home care and not adoption; mortality surveillance was extended into adulthood; standard estimates of association (eg, relative risk, odds ratios, or hazard ratios) and variance (eg, CIs and SE) were provided; the study appeared in a peer-reviewed journal; and the study was published in English. An adapted Cochrane Risk of Bias Tool was used to assess study quality. We extracted estimates of association and variance from qualifying studies and augmented these findings with analyses of unpublished data from individual participants in two UK birth cohorts—ie, the 1958 and 1970 studies (total n=21 936). We computed hazard ratios with accompanying 95% CIs for care and each health outcome separately for each study, and then pooled the results using a random-effects meta-analysis. This review is registered at PROSPERO, CRD42021254665.FindingsWe identified 210 potentially eligible published articles, of which 14 met our inclusion criteria (two studies were unpublished). Of 3 223 580 individuals drawn from 13 studies, those who were exposed to care in childhood had twice the risk of total mortality in adulthood relative to those without a history of care in childhood (summary risk ratio 2·21 [95% CI 1·62–3·02]), with study-specific estimates varying between 1·04 and 5·77 (I2 =98%). Despite some attenuation, this association remained following adjustment for other measures of early-life adversity; extended into middle and older age; was stronger in higher-quality studies; and was of equal magnitude according to sex, geographical region, and birth year. There was some suggestion of sensitive periods of exposure to care, whereby individuals who entered state care for the first time in adolescence (2·47 [0·98–6·52]) had greater rates of mortality than those doing so early in the life course (1·75 [1·25–2·45]). In four studies including 534 890 people, children in care had more than three times the risk of completed suicide in adulthood relative to their unexposed peers (3·35 [2·41–4·68]), with study-specific estimates ranging between 2·42 and 5·85 (I2=72%). The magnitude of this association was weaker after adjustment for multiple covariates; in men than in women; and in lower-quality studies.InterpretationOur results for adult mortality suggest child protection systems, social policy, and health services following care graduation are insufficient to mitigate the adverse experiences that might have preceded placement into care and those that might accompany it.FundingNone.

Is L5/S1 interbody fusion necessary in long-segment surgery for adult degenerative scoliosis? A systematic review and meta-analysis.

There is no consensus regarding the best surgical strategy at the lumbosacral junction (LSJ) in long constructs for adult spinal deformity (ASD). The use of interbody fusion (IF) has been advocated to increase fusion rates, with additional pelvic fixation (PF) typically recommended. The actual benefit of IF even when extending to the pelvis, however, has not been vigorously analyzed. The goal of this work was to better understand the role of IF, specifically with respect to arthrodesis, when extending long constructs to the ilium. A systematic review of the PubMed and Cochrane databases was performed to identify the relevant studies in English, addressing the management of LSJ in long constructs (defined as ≥ 5 levels) in ASD. The search terms used were as follows: "Lumbosacral Junction," "Long Constructs," "Long Fusion to the Sacrum," "Sacropelvic Fixation," "Interbody Fusion," and "Iliac Screw." The authors excluded technical notes, case reports, literature reviews, and cadaveric studies; pediatric populations; pathologies different from ASD; studies not using conventional techniques; and studies focused only on alignment of different levels. The PRISMA protocol was used. The authors found 12 retrospective clinical studies with a total of 1216 patients who were sorted into 3 different categories: group 1, using PF or not (n = 6); group 2, using PF with or without IF (n = 5); and group 3, from 1 study comparing anterior lumbar interbody fusion versus transforaminal lumbar interbody fusion. Five studies in group 1 and 4 in group 2 had pseudarthrosis rate as primary outcome and were selected for a quantitative analysis. Forest plots were used to display the risk ratio, and funnel plots were used to look at the risk of publication bias. The summary risk ratios were 0.36 (0.23-0.57, p < 0.001) and 1.03 (0.54-1.96, p = 0.94) for the PF and IF, respectively; there is a protective effect of overall pseudarthrosis for using PF in long constructs for ASD surgeries, but not for using IF. The long-held contention that L5/S1 IF is always advantageous in long-construct deformity surgery is not supported by the current literature. Based on the findings from this systematic review and meta-analysis, PF with or without additional L5/S1 interbody grafting demonstrates similar overall construct pseudarthrosis rates. The added risk and costs associated with IF, therefore, should be more closely considered on a case-by-case basis.

Safety of High-Dose Vitamin D Supplementation Among Children Aged 0 to 6 Years

Several health benefits of vitamin D have been suggested; however, the safety of high-dose supplementation in early childhood is not well described. To systematically assess the risk of adverse events after high-dose supplementation with vitamin D reported in published randomized clinical trials. PubMed and ClinicalTrials.gov were searched through August 24, 2021. Randomized clinical trials of high-dose vitamin D supplementation in children aged 0 to 6 years, defined as greater than 1000 IU/d for infants (aged 0-1 year) and greater than 2000 IU/d for children aged 1 to 6 years. Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline, 2 reviewers independently extracted the data from the eligible studies. Summary risk ratio (RR), 95% CI, and P values were derived from random-effects meta-analysis. Adverse events, serious adverse events (SAEs), and/or levels of 25-hydroxyvitamin D, calcium, alkaline phosphatase, phosphate, parathyroid hormone, and/or the ratio of urine calcium to creatinine levels. A total of 32 randomized clinical trials with 8400 unique participants were included. Different clinical outcomes of children receiving high-dose vitamin D supplements ranging from 1200 to 10 000 IU/d and bolus doses from 30 000 IU/week to a single dose of 600 000 IU were evaluated. Eight studies with 4612 participants were eligible for meta-analysis using a control group receiving either low-dose vitamin D supplementation (≤400 IU/d) or placebo when investigating the risk of SAEs such as hospitalization or death. No overall increased risk of SAEs in the high-dose vitamin D vs control groups was found (RR, 1.01 [95% CI, 0.73-1.39]; P = .89, I2 = 0%). In addition, risk of hypercalcemia (n = 726) was not increased (RR, 1.18 [95% CI, 0.72-1.93]; P = .51). Clinical adverse events potentially related to the vitamin D supplementation reported in the studies were rare. This meta-analysis and systematic review found that high-dose vitamin D supplementation was not associated with an increased risk of SAEs in children aged 0 to 6 years, and that clinical adverse events potentially related to the supplementation were rare. These findings suggest that vitamin D supplementation in the dose ranges of 1200 to 10 000 IU/d and bolus doses to 600 000 IU to young children may be well tolerated.

Impact of occupational pesticide exposure assessment method on risk estimates for prostate cancer, non-Hodgkin’s lymphoma and Parkinson’s disease: results of three meta-analyses

Assessment of occupational pesticide exposure in epidemiological studies of chronic diseases is challenging. Biomonitoring of current pesticide levels might not correlate with past exposure relevant to disease aetiology, and indirect...

Pregabalin add-on for drug-resistant focal epilepsy.

Pregabalin add-on for drug-resistant focal epilepsy.

Comparative efficacy and safety of vaccines to prevent seasonal influenza: A systematic review and network meta-analysis

SummaryBackgroundInfluenza is one of the most common respiratory viral infections worldwide. Numerous vaccines are used to prevent influenza. Their selection should be informed by the best available evidence. We aimed to estimate the comparative efficacy and safety of seasonal influenza vaccines in children, adults and the elderly.MethodsWe conducted a systematic review and network meta-analysis (NMA). We searched the Cochrane Library Central Register of Controlled Trials, MEDLINE and EMBASE databases, and websites of regulatory agencies, through December 15th, 2020. We included placebo- or no vaccination-controlled, and head-to-head randomized clinical trials (RCTs). Pairs of reviewers independently screened the studies, abstracted the data, and appraised the risk of bias in accordance to the Cochrane Handbook for Systematic Reviews of Interventions. The primary outcome was laboratory-confirmed influenza. We also synthesized data for hospitalization, mortality, influenza-like illness (ILI), pneumonia or lower respiratory-tract disease, systemic and local adverse events (AEs). We estimated summary risk ratios (RR) using pairwise and NMA with random effects. This study is registered with PROSPERO, number CRD42018091895.FindingsWe identified 13,439 citations. A total of 231 RCTs were included after screening: 11 studies did not provide useful data for the analysis; 220 RCTs [100,677 children (< 18 years) and 329,127 adults (18–60 years) and elderly (≥ 61 years)] were included in the NMA. In adults and the elderly, all vaccines, except the trivalent inactivated intradermal vaccine (3-IIV ID), were more effective than placebo in reducing the risk of laboratory-confirmed influenza, with a RR between 0.33 (95% credible interval [CrI] 0.21–0.55) for trivalent inactivated high-dose (3-IIV HD) and 0.56 (95% CrI 0.41–0.74) for trivalent live-attenuated vaccine (3-LAIV). In adults and the elderly, compared with trivalent inactivated vaccine (3-IIV), no significant differences were found for any, except 3-LAIV, which was less efficacious [RR 1.41 (95% CrI 1.04–1.88)]. In children, compared with placebo, RR ranged between 0.13 (95% CrI 0.03–0.51) for trivalent inactivated vaccine adjuvanted with MF59/AS03 and 0.55 (95% CrI 0.36–0.83) for trivalent inactivated vaccine. Compared with 3-IIV, 3-LAIV and trivalent inactivated adjuvanted with MF59/AS03 were more efficacious [RR 0.52 (95% CrI 0.32–0.82) and RR 0.23 (95% CrI 0.06–0.87)] in reducing laboratory-confirmed influenza. With regard to safety, higher systemic AEs rates after vaccination with 3-IIV, 3-IIV HD, 3-IIV ID, 3-IIV MF59/AS03-adj, quadrivalent inactivated (4-IIV), quadrivalent adjuvanted (4-IIV MF59/AS03-adj), quadrivalent recombinant (4-RIV), 3-LAIV or quadrivalent live attenuated (4-LAIV) vaccines were noted in adults and the elderly [RR 1.5 (95% CrI 1.18–1.89) to 1.15 (95% CrI 1.06–1.23)] compared with placebo. In children, the systemic AEs rate after vaccination was not significantly higher than placebo.InterpretationAll vaccines cumulatively achieved major reductions in the incidence of laboratory-confirmed influenza in children, adults, and the elderly. While the live-attenuated was more efficacious than the inactivated vaccine in children, many vaccine types can be used in adults and the elderly.FundingThe directorate general of welfare, Lombardy region.

Serum uric acid levels and diabetic kidney disease in patients with type 2 diabetes mellitus: A dose-response meta-analysis

ObjectiveOur study aimed to assess the existing evidence on whether serum uric acid (SUA) levels are associated with diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM). MethodsWe conducted a systematic search of articles up to October 2021 in Medline, Embase, The Cochrane Library and Web of Science that estimated DKD by SUA levels in patients with T2DM. Pooled relative risks with 95% CI were calculated using random effects models ResultsA total of eight cohort studies involving 25,741 T2DM patients were included. Meta-analysis showed that compared the highest with the lowest category of SUA level, the summary risk ratios were 2.04 (95%CI 1.43–2.92, P < 0.001). The linear dose-response analysis revealed that the risk of DKD increased by 24% for each 1 mg/dl increase of SUA. The non-linear dose-response analysis also showed a significant relevance between SUA and the risk of DKD in patients with type 2 diabetes mellitus (P < 0.001). ConclusionsSerum uric acid is associated with an increased risk of diabetic kidney disease in patients with type 2 diabetes mellitus. Serum uric acid level could be a good indicator for predicting diabetic kidney disease in patients with type 2 diabetes mellitus.

Antiepileptic drugs for the primary and secondary prevention of seizures after stroke.

Seizures after stroke are an important clinical problem and may result in poor outcomes. The indications of antiepileptic drugs (AEDs) for seizure prophylaxis after stroke remain unclear. This is an updated version of the Cochrane Review previously published in 2014. To assess the effects of AEDs for the primary and secondary prevention of seizures after stroke. For primary prevention, we aimed to assess whether AEDs reduce the likelihood of seizures in people who have a stroke but do not have a seizure. For secondary prevention, we aimed to assess whether AEDs reduce the likelihood of further seizures in people who have a stroke and at least one post-stroke seizure. We searched the following databases on 9 March 2021: Cochrane Register of Studies (CRS Web), MEDLINE (Ovid, 1946 to March 08, 2021). CRS Web includes randomised or quasi-randomised controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organisation International Clinical Trials Registry Platform (ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), and the Specialised Registers of Cochrane Review Groups including Epilepsy and Stroke. We also checked the reference lists of articles retrieved from these searches. We selected randomised and quasi-randomised controlled studies that recruited participants with a clinical diagnosis of stroke, either ischaemic or haemorrhagic. We excluded studies that only recruited participants with subarachnoid haemorrhage, subdural haemorrhage, extradural haemorrhage, or other non-stroke diagnoses such as tumour- or infection-related infarction or haemorrhage. We also excluded studies that recruited only participants who had undergone neurosurgery. We included participants of all ages suffering any seizure type who were assigned to AEDs or placebo groups. In accordance with standard methodological procedures expected by The Cochrane Collaboration, two review authors independently assessed trials for inclusion before evaluating trial risk of bias and extracting relevant data. The primary outcome assessed was the proportion of participants who experienced seizures in the follow-up period. We presented results as summary risk ratios (RRs) with 95% confidence intervals (CIs) for dichotomous outcomes and mean differences (MDs) with 95% CIs for continuous outcomes. Where we had sufficient data, we calculated random-effects (Mantel-Haenszel) meta-analyses for dichotomous outcomes; otherwise, we reported results narratively. We used the I2 statistic to analyse statistical heterogeneity. We planned to use funnel plots to assess publication bias in meta-analyses with at least 10 included studies. We used the GRADE approach to assess the certainty of the evidence. Two studies with a total of 856 subjects were included. AEDs were not shown to be effective in primary prophylaxis of post-stroke seizure (RR 0.65, 95% CI 0.34 to 1.26; 2 studies, 856 participants; moderate-certainty evidence). The first study was a randomised double-blind study comparing valproic acid with placebo for primary seizure prevention up to one year after stroke. The study included 72 adults with intracerebral haemorrhage. There was no difference in the risk of post-stroke seizures (RR 0.88, 95% CI 0.35 to 2.16) or of death (RR 1.20, 95% CI 0.40 to 3.58). The second study was a substudy on the use of diazepam in acute stroke. It was a randomised double-blind study, comparing a three-day diazepam treatment versus placebo for primary seizure prevention up to three months after stroke in 784 adults with acute stroke. There was no evidence of a difference in the risk of post-stroke seizures for all stroke or subgroups of haemorrhagic or ischaemic stroke (RR for all stroke 0.47, 95% CI 0.18 to 1.22). In a subgroup analysis of anterior circulation cortical infarcts, primary prophylaxis with diazepam was associated with a reduced risk of post-stroke seizures (RR 0.21, 95% CI 0.05 to 0.95). Risks of mortality did not differ between the diazepam and the placebo group at two weeks (RR 0.84, 95% CI 0.56 to 1.26) and three months follow-up (RR 0.95, 95% CI 0.72 to 1.26). We assessed both studies to be at a low overall risk of bias. Using the GRADE approach, we assessed the overall certainty of the evidence as low to moderate. There is insufficient evidence to support the routine use of AEDs on the primary and secondary prevention of seizures after stroke. Further well-conducted studies are warranted for this important clinical problem.

Characteristics of Clinical Trials Evaluating Biosimilars in the Treatment of Cancer

Biologics account for almost half of US drug spending but may be subject to competitive pricing pressures by US Food and Drug Administration-approved biosimilars. The extent of the preapproval clinical testing that is needed and how these biosimilars compare with the originator biologic products remain critical issues in establishing a vibrant biosimilar market. To analyze the design of cancer biosimilar efficacy studies compared with the reference drug pivotal trials and provide summary risk ratio estimates for each cancer type drug subgroup. A systematic search was performed of articles and abstracts published using Embase, PubMed/MEDLINE, and ClinicalTrials.gov, last updated April 18, 2021. All studies or abstracts in English comparing a disease-modifying cancer biologic and its biosimilar and reporting efficacy or surrogate efficacy results were included. Outcome estimates and study characteristics were extracted from each study. Among biosimilar efficacy studies, random-effects meta-analyses were performed for each cancer type molecule outcome subgroup, calculating pooled relative estimates and 95% CIs. Study characteristics, such as population size, blinding, and randomization, were compared between biosimilar trials and those of reference drugs. Risk ratio estimates for relative change to surrogate measures (eg, progression-free survival) were collected for biosimilars and their reference products. A total of 31 cancer biosimilar studies of 3 reference products involving 12 310 patients were included. In all 7 subgroups, the biosimilars analyzed were indistinguishable from their reference drug on surrogate efficacy. Six reference drug trials were included, involving 1811 patients. On average, biosimilar studies involved more patients than reference drug trials (mean number of patients, 397 vs 302), were more likely to be randomized clinical trials rather than single-group or observational studies (100% [31 of 31] vs 50% [3 of 6]), and were more likely to be double blind rather than open label (84% [26 of 31] vs 17% [1 of 6]). This systematic review and meta-analysis found that the biosimilars for the cancer drugs in this sample were subjected to rigorous clinical evaluations, and the results were statistically indistinguishable from those of original products across drugs, cancer types, and outcome measures.

Fish Consumption and Colorectal Cancer Risk: Meta-Analysis of Prospective Epidemiological Studies and Review of Evidence from Animal Studies.

Simple SummaryWe meta-analyzed prospective epidemiological studies reporting on the association between fish consumption and colorectal cancer (CRC) risk among humans and reviewed preclinical studies that examined the link between fish components and colorectal carcinogenesis in animals. By pooling results from 25 studies (encompassing over 25,000 CRC cases) published up to November 2020, we found convincing evidence that increased fish consumption may protect from CRC development among humans. The review of animal studies allowed identifying several biological mechanisms able to explain the associations that have emerged in human populations. Dietary recommendations for cancer prevention should incorporate the evidence from this literature review and meta-analysis.Background: Epidemiological studies on the association between fish consumption and colorectal cancer (CRC) risk have yielded inconsistent results, despite evidence from preclinical studies that long-chain ω-3 polyunsaturated fatty acids inhibit colorectal carcinogenesis. We conducted a meta-analysis of prospective epidemiological studies investigating the association between fish consumption and CRC risk among humans and reviewed studies examining the link between fish components and colorectal carcinogenesis in animal models. Methods: We included studies published until November 2020. We calculated the summary risk ratio (SRR) and 95% confidence intervals (CI) through random effects meta-analysis models in order to summarize evidence from studies among humans. Results: Twenty-five prospective epidemiological studies encompassing 25,777 CRC cases were included. Individuals in the highest (vs. lowest) category of fish consumption had a significantly reduced risk of CRC (SRR 0.94, 95%CI 0.89–0.99). In dose–response meta-analysis, a 50-g increment in the daily consumption of fish was associated with a statistically significant 4% reduction in CRC risk (SRR 0.96, 95%CI 0.92–0.99). Preclinical studies (n = 25) identified multiple mechanisms of action of fish and fish components on colorectal carcinogenesis. Conclusions: Dietary recommendations for cancer prevention should take into account the evidence from epidemiological and preclinical studies that increasing fish consumption may be effective in preventing CRC.

Reduced lung function predicts risk of incident type 2 diabetes: insights from a meta-analysis of prospective studies.

Epidemiological studies have repeatedly investigated the association between reduced pulmonary function and incident type 2 diabetes mellitus (T2DM). However, the results have been inconsistent. This meta-analysis aimed to clarify this association with prospective cohort studies. We searched PubMed, Web of Science (ISI), and Google Scholar for all studies (in English) reporting reduced lung function with a risk of T2DM. The measures of lung function included percentage of forced vital capacity for predicted values (FVC%pre), percentage of forced expiratory volume in the first second after expiration for predicted values (FEV1%pre) and FEV1-to-FVC ratio%. Summary risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using fixed-effects or random-effects meta-analyses. A total of 5,480 incident T2DM patients among 88,799 individuals were identified from nine prospective cohort studies. Compared to the highest category of FVC%pre and FEV1%pre, the lowest category of FVC%pre and FEV1%pre were significantly associated with increased incident T2DM risk (FVC%pre: RR = 1.49, 95% CI: 1.39-1.59; FEV1%pre: RR = 1.52, 95% CI: 1.42-1.62). However, no significant relationship was found between the FEV1/FVC ratio and incident T2DM risk (RR = 1.01, 95% CI: 0.91-1.13). Current evidence suggests that restrictive rather than obstructive impairment of lung function is significantly associated with the incidence of T2DM. Further research is warranted to explore potential mediators of this relationship.

Active Versus Conventional Side Branch Protection Strategy for Coronary Bifurcation Lesions.

The side branch (SB) provisional stenting strategy is currently the recommended approach for most coronary bifurcation lesions. However, this strategy may result in SB deterioration, which is associated with an increased incidence of periprocedural myocardial infarction (PMI) and may adversely affect the long-term prognosis. Various techniques for SB protection (SB-P) have been developed to reduce SB occlusion and improve the clinical prognosis. This meta-analysis was performed to compare the outcomes of an active SB-P strategy of jailed balloon technique, balloon-stent kissing technique, and jailed Corsair technique versus the conventional SB-P strategy based on jailed wire technique.This meta-analysis included 5 studies (4 randomized and 1 observational) involving a total of 1,174 patients in whom the active and conventional SB-P strategies were compared. Fixed- and random-effects models were used to calculate summary risk ratios (RRs).The risk of SB occlusion was significantly lower in active SB-P strategy [RR 0.47, 95% confidence interval (CI) 0.30-0.73 in fixed-effect model; RR 0.52, 95% CI 0.31-0.87 in random-effect model]. The risk of PMI was similar between the two strategies (RR 0.63, 95% CI 0.30-1.33 in fixed-effect model; RR 0.71, 95%CI 0.20-2.48 in random-effect model). The rate of long-term major adverse cardiovascular events was similar between the groups (RR 0.48, 95% CI 0.15-1.48 in fixed-effect model; RR 0.49, 95% CI 0.16-1.52 in random-effect model).The active SB-P strategy in coronary bifurcation lesions is associated with reduced SB deterioration, but it does not decrease PMI or improve the long-term prognosis.

Risk of bleeding with ticagrelor in elderly patients over 75 years old: A systematic review and meta-analysis.

Background:Bleeding is an untoward outcome in the management of elderly patients with acute coronary syndrome (ACS). Although the potent oral P2Y12 inhibitor, ticagrelor is clinically beneficial, its association with bleeding events in elderly ACS patients (≥75 years) is poorly understood.Methods:We conducted a systematic search of 7 databases up to May 20, 2020 to identify studies which examined the risk of bleeding (defined according to each study) among elderly ACS patients (≥75 years) receiving ticagrelor compared to clopidogrel. Summary risk ratios (RR) were estimated using the random effects model.Results:Eight studies consisting of 5 observational studies and 3 randomized controlled trials involving 7032 elderly patients met the eligibility criteria. The mean age of the patients was 77.8 years, and the mean follow-up duration was 12 months. Overall, the pooled RRs showed higher risk of a bleeding event with ticagrelor compared to clopidogrel (RR 1.20, 95% confidence interval [95% CI] 1.03–1.40; P = .017). No statistically significant heterogeneity was observed among the studies (Q = 6.93; P = .44; I2 = 0). Also, pooled RRs did not show a higher risk of major bleeding (RR 1.32, 95% CI 0.91–1.92; P = .15) or minor bleeding (RR 1.09, 95% CI 0.76–1.58; P = .64) when comparing the ticagrelor to the clopidogrel group.Conclusions:There is a 20% increased risk of a bleeding event in elderly ACS patients treated with ticagrelor compared to clopidogrel; for such patients, clopidogrel may be considered as an alternative agent to ticagrelor due to its lower risk of bleeding.