Risk Of Overall Adverse Events Research Articles

Effectiveness and Safety of Dupuytren Contracture Treatments: A Systematic Review and Meta-Analysis Using the GRADE Approach.

There is currently no consensus on the optimal treatment for Dupuytren contracture. Prior meta-analyses have been limited by suboptimal data synthesis methodologies. We conducted an updated evidence review comparing the effectiveness and safety of percutaneous needle fasciotomy (PNF), collagenase clostridium histolyticum (CCH), and limited fasciectomy (LF) using the GRADE approach. CENTRAL, MEDLINE, and Embase were searched for randomized controlled trials comparing outcomes following PNF, CCH, and LF for Dupuytren contracture treatment. Outcomes of interest included residual contracture, recurrence rate, hand function, pain, global satisfaction, and adverse events. Time points included 3-months, 1-year, and 2-3 years. Seventeen publications (1,010 patients) were included. High to moderate certainty evidence showed no clinically important difference in long-term contracture reduction (PNF vs. LF (mean difference (MD): 7.6°; 95% CI: 1.8°-13.4°), CCH vs. LF (MD: 4.8°; 95% CI: -1.3°-10.9°)). Moderate certainty evidence indicated that LF provides the lowest risk of long-term recurrence (PNF vs. LF (relative risk (RR): 12.3; 95% CI: 1.6-92.4), CCH vs. LF (RR: 9.5; 95% CI 1.2-73.4)), LF has a higher risk of serious adverse events than PNF (RR: 0.5; 95% CI 0.3-0.9), and CCH has a higher risk of overall adverse events than PNF (RR: 4.8; 95% CI 2.9-7.0). CCH, PNF, and LF are equally effective in long-term contracture reduction. However, LF yields more durable results at a higher risk of rare but serious adverse events. Current evidence suggests the use of PNF over CCH. However, ultimate treatment decisions should be tailored to individual patient preferences.

Safety profile of sacituzumab govitecan in patients with breast cancer: A systematic review and meta-analysis.

e13106 Background: Sacituzumab govitecan (SG), a first-in-class TROP-2-directed antibody conjugated to a topoisomerase inhibitor, has shown antitumor activity across various breast cancer (BC) subtypes. Following SG approval for metastatic triple negative breast cancer (TNBC) and its broad use, understanding SG’ safety profile is crucial. Hence, we conducted a systematic review and meta-analysis to evaluate the safety and tolerability of SG in patients with BC. Methods: We comprehensively searched PubMed, Embase, and Cochrane databases, and ASCO and ESMO websites for clinical trials assessing the safety of SG in BC patients. Outcomes of interest included treatment-related adverse events (TRAEs) of any grade, grade 3/4, adverse events (AEs) leading to death, and AEs leading to SG dose reduction or discontinuation. All analyses were performed in R software (v.4.2.2) using random effects models. Heterogeneity was assessed using I2 test. Results: A total of 1,325 patients from six studies – three randomized clinical trials (RCTs) and three non-RCTs – were included. Median age of population ranged from 47 to 56 years. Most had metastatic disease (86%, n=1187), and triple-negative BC (48.6%, n=670). Regarding therapies, 798 patients received SG and 527 had treatment of physician's choice (TPC). In the pooled analysis of 748 patients on SG, the overall risk of AEs was 100% (95% CI 99-100%). The estimated risk of the most common all grade AEs were neutropenia (66%), anemia (44%), nausea (56%), vomiting (30%), fatigue (46%), constipation (17%), diarrhea (45%), and alopecia (46%), as described (Table). The risk of grade 3/4 AEs among 748 patients on SG was 55% (95% CI 36-74%). Neutropenia was the most important grade ≥3 AE, with a estimated frequency of 47%; followed by anemia and diarrhea, with an incidence of at 9% and 7%, respectively. The incidence of all other grade 3/4 AEs (e.g. anemia, vomiting, leukopenia, fatigue, constipation, and diarrhea) was below 10%. Dose reduction and discontinuation were observed in 14.4% and 2.9% of patients, respectively. Toxicity-related deaths occurred in six patients (0.4%). In a comparative sensitivity analysis of RCTs only, SG had significantly higher toxicity than TCPs, all grade AEs (OR 12.30 95%CI 1.68-89.87, p=0.01), and grade >3 AEs (OR 1.69 95%CI 1.25-2.28, p=0.0006). Conclusions: In this systematic review and meta-analysis, SG was associated with a high incidence of AEs. Neutropenia is a notable and potentially serious adverse event. Toxicity associated with SG may be addressed through close monitoring and early management. [Table: see text]

Is tumor necrosis factor-α monoclonal therapy with proactive therapeutic drug monitoring optimized for inflammatory bowel disease? Network meta-analysis.

The efficacy and safety of anti-tumor necrosis factor-α (TNF-α) monoclonal antibody therapy [adalimumab (ADA) and infliximab (IFX)] with therapeutic drug monitoring (TDM), which has been proposed for inflammatory bowel disease (IBD) patients, are still controversial. To determine the efficacy and safety of anti-TNF-α monoclonal antibody therapy with proactive TDM in patients with IBD and to determine which subtype of IBD patients is most suitable for proactive TDM interventions. As of July 2023, we searched for randomized controlled trials (RCTs) and observational studies in PubMed, Embase, and the Cochrane Library to compare anti-TNF-α monoclonal antibody therapy with proactive TDM with therapy with reactive TDM or empiric therapy. Pairwise and network meta-analyses were used to determine the IBD patient subtype that achieved clinical remission and to determine the need for surgery. This systematic review and meta-analysis yielded 13 studies after exclusion, and the baseline indicators were balanced. We found a significant increase in the number of patients who achieved clinical remission in the ADA [odds ratio (OR) = 1.416, 95% confidence interval (CI): 1.196-1.676] and RCT (OR = 1.393, 95%CI: 1.182-1.641) subgroups and a significant decrease in the number of patients who needed surgery in the proactive vs reactive (OR = 0.237, 95%CI: 0.101-0.558) and IFX + ADA (OR = 0.137, 95%CI: 0.032-0.588) subgroups, and the overall risk of adverse events was reduced (OR = 0.579, 95%CI: 0.391-0.858) according to the pairwise meta-analysis. Moreover, the network meta-analysis results suggested that patients with IBD treated with ADA (OR = 1.39, 95%CI: 1.19-1.63) were more likely to undergo TDM, especially in comparison with patients with reactive TDM (OR = 1.38, 95%CI: 1.07-1.77). Proactive TDM is more suitable for IBD patients treated with ADA and has obvious advantages over reactive TDM. We recommend proactive TDM in IBD patients who are treated with ADA.

Efficacy and Safety of Insulin Degludec/Insulin Aspart versus Biphasic Insulin Aspart 30 in Patients with Type 2 Diabetes: A Meta-Analysis of Randomized Controlled Trials.

We systematically reviewed and analyzed the efficacy and safety of insulin degludec/insulin as-part (IDegAsp) versus biphasic insulin aspart 30 (BIAsp 30) in patients with type 2 diabetes (T2D). We used computers to search the Embase, PubMed, Clinical Trials, and the Cochrane Library database, and collected randomized controlled trials (RCTs) on the treatment of IDegAsp versus BIAsp 30 in T2D patients. The research period was from the establishment of the database to May 19, 2023. We used Review Manager 5.20 statistical software for systematic meta-analysis. We included 8 RCTs with 2281 participants. IDegAsp was better to BIAsp30 in improving fasting plasma glucose (FPG) levels (P<0.001) and reducing the endpoint daily average insulin dose (P<0.01). Furthermore, compared with BIAsp30, IDegAsp significantly reduced the risk of nocturnal hypoglycemic events (P<0.001). However, there was no significant difference in the improvement of body weight change (P=0.99), glycosylated hemoglobin (P=0.50), the overall risk of hypoglycemic events (P=0.57) and adverse events (P=0.89) between the two groups. Compared with BIAsp30, IDegAsp could significantly reduce FPG levels, insulin dosage, and the risk of nocturnal hypoglycemic events in T2D patients, without increasing the overall risk of adverse events.

Identifying risk factors of anti-TNF induced skin lesions and other adverse events in paediatric patients with inflammatory bowel disease.

While higher infliximab (IFX) trough concentrations (TCs) are associated with better outcomes in patients with inflammatory bowel disease (IBD), they could pose a risk for adverse events (AEs), including IFX-induced skin lesions. Therefore, we studied correlations between IFX TCs and occurrence of AEs in paediatric IBD patients. In this single-centre study, all children with Crohn's disease (CD) and ulcerative colitis (UC) receiving IFX maintenance therapy who underwent proactive drug monitoring between March 2015 and August 2022 were included. IFX doses/intervals/TCs and patient characteristics were systematically registered, as well as AEs and skin lesions appearance. A total of 109 patients (72 CD and 37 UC) contributed 2913 IFX TCs. During a median follow-up of 3.0 [1.5-4.5] years, we observed 684 AEs in 101 patients and 49 skin lesions in 35 patients. There was no significant difference (p = .467) in median TCs between patients with and without skin lesions. However, higher median IFX doses were associated with an increased hazard rate of skin lesions [HR 1.084 (1.024-1.148), p = .005], in addition to female sex [2.210 (1.187-5.310), p = .016] and diagnosis of CD [1.695 (1.241-1.877), p = .011]. Considering IFX therapeutic TC cut-offs of 5.0 and 9.0 µg/mL, there was no significant difference in AE rate (p = .749 and p = .833, respectively). Also, no significant association between IFX doses and AE rate (p = .159). Increasing the IFX dose to achieve therapeutic TCs may not increase the overall risk of AEs in paediatric IBD patients. However, concerns arise regarding the risk of skin lesions, especially in female CD patients.

Safety of biologic therapy in combination with methotrexate in moderate to severe psoriasis: a cohort study from the BIOBADADERM registry.

Safety is an important consideration in decisions on treatment for patients with moderate-to-severe psoriasis and the study of drug safety is the main purpose of the BIOBADADERM registry. The combination of a biologic agent and a conventional systemic drug [generally methotrexate (MTX)] is a common treatment in clinical practice. However, there is a paucity of evidence from real-world practice on the safety of such combination regimens in the treatment of psoriasis. The primary objective of this study was to ascertain whether the use of regimens combining biologic drugs with MTX in the management of moderate-to-severe psoriasis increases the risk of adverse events (AEs) or serious AEs (SAEs). We compared monotherapy using tumour necrosis factor (TNF), interleukin (IL)-17 and IL-23 inhibitors with the use of the same drugs in combination with MTX. Using data from the BIOBADADERM registry, we compared biologic monotherapies with therapies that were combined with MTX. We estimated adjusted incidence rate ratios (aIRR) using a random effects Poisson regression with 95% confidence intervals for all AEs, SAEs, infections and serious infections and other AEs by system organ class. We analysed data from 2829 patients and 5441 treatment cycles, a total of 12 853 patient-years. The combination of a biologic with MTX was not associated with statistically significant increases in overall risk of AEs or SAEs in any treatment group. No increase in the total number of infections or serious infections in patients receiving combined therapy was observed for any group. However, treatment with aTNF inhibitor combined with MTX was associated with an increase in the incidence of gastrointestinal AEs (aIRR 2.50, 95% CI 1.57-3.98; P < 0.002). The risk of AEs and SAEs was not significantly increased in patients with moderate-to-severe psoriasis receiving different classes of biologic drugs combined with MTX compared with those on biologic monotherapy.

Comparing Efficacy and Safety of Different Doses of Tirzepatide for the Treatment of Type 2 Diabetes Mellitus: A Meta-Analysis of Randomized Controlled Trials.

Our study assessedthe efficacyand safety of the three primary tirzepatide (TZP) doses, 5 mg, 10 mg, and 15 mg using network meta-analysis to assess their relative impact on type 2 diabetes mellitus (T2DM) treatment.This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Two authors independently screened online databases, including PubMed, Cochrane Library, and Embase. We employed the keywords "Type 2 diabetes OR T2DM or diabetes" AND "Tirzepatide OR LY3298176 OR twincretin OR dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist" AND "randomized controlled trial". The outcomes evaluated in this study comprised changes in hemoglobin (Hb)A1c levels from baseline (%), changes in weight from baseline (Kg), changes in fasting serum glucose from baseline (mg/dL), and occurrences of serious adverse events (SAE), adverse events (AE) and major adverse cardiovascular events (MACE). A total of eight studies met the inclusion criteria and were included in this meta-analysis. Our findings suggest that among the evaluated doses, TZP at 15 mg demonstrated superior effectiveness in reducing HbA1c, weight, and fasting serum glucose compared to doses of 10 mg and 5 mg. Notably, the reduction in HbA1c and weight showed a dose-dependent trend, with the 15 mg dose achieving the most substantial benefits. The safety analysis indicated that while serious adverse events and major adverse cardiovascular events (MACE) did not significantly differ among the three doses, the risk of overall adverse events was notably higher in the 10 mg and 15 mg TZP groups compared to the 5 mg group.

A Systematic Review and Meta-Analysis on the Efficacy and Safety of Finerenone Therapy in Patients with Cardiovascular and Chronic Kidney Diseases in Type 2 Diabetes Mellitus.

The purpose of this study is to assess the safety and efficacy of finerenone therapy in type 2 diabetes mellitus (T2DM) patients with cardiovascular and chronic renal diseases. This meta-analysis assesses the efficacy and safety of finerenone in the treatment of diabetic kidney disease (DKD).A comprehensive search of PubMed, Embase, and Google Scholar databases was performed to identify relevant randomized controlled trials (RCTs). To quantify the effects of finerenone, the analysis included the estimation of aggregated mean differences (MDs) and relative risks (RRs), as well as 95% confidence intervals (CIs). This meta-analysis included seven double-blind trials with patients suffering from chronic kidney disease (CKD) and T2D. Participants received finerenone or a placebo was assigned at random. The primary efficacy outcomes were cardiovascular mortality, non-fatal myocardial infarction, non-fatal stroke, hospitalization for heart failure, kidney failure, a sustained 57% decrease in the estimated glomerular filtration rate from baseline over four weeks, or renal death. Among the 39,995 patients included in the analysis, finerenone treatment was associated with a lower risk of cardiovascular and renal-related mortality compared to placebo (RR = 0.86 (0.80, 0.93), p = 0.0002; I-squared statistic(I2)= 0%) and (RR = 0.56 (0.17, 1.82), p = 0.34; I2= 0%). In addition, finerenone treatment was associated with a marginally reduced risk of serious adverse events (RR = 0.95 (0.92, 0.97), p = 0.0001; I2= 0%), although no significant difference in the overall risk of adverse events was observed between the two groups (RR = 1.00 (0.99, 1.01), p = 0.56; I2= 0%). This study's findings suggest that finerenone administration can reduce the risk of end-stage kidney disease, renal failure, cardiovascular mortality, and hospitalization. Patients with both T2DM and CKD are therefore advised to consider finerenone therapy.

Topical diquafosol versus hyaluronic acid for the treatment of dry eye disease: a meta-analysis of randomized controlled trials.

Diquafosol enhances fluid transfer and mucin secretion on ocular surface, which has been suggested as an effective treatment for dry eye disease (DED). The aim of the systematic review and meta-analysis was to compare the efficacy and safety of topical diquafosol versus hyaluronic acid (HA) for DED. Relevant randomized controlled trials were obtained via search of electronic including PubMed, Embase, Cochrane Library, and Web of Science. A random-effects model was used to pool the results after incorporating the influence of potential heterogeneity. A total of nine RCTs involving 1295 patients with DED were included in the meta-analysis. Compared to treatment with 0.1% HA, topical treatment with 3% diquafosol significantly improved the Ocular Surface Disease Index (mean difference (MD): - 3.59, 95% confidence interval (CI): - 4.68 to - 2.50, p < 0.001; I2 = 6%), results of Schirmer's test (MD: 1.08 mm, 95% CI: 0.41 to 1.76, p = 0.002; I2 = 0%), tear breakup time (MD: 0.60 s, 95% CI: 0.20 to 0.99, p = 0.003; I2 = 63%), corneal fluorescein staining score (MD: - 0.20, 95% CI: - 0.37 to - 0.03, p = 0.02; I2 = 58%), and ocular rose bengal staining score (MD: - 0.62, 95% CI: - 0.88 to - 0.35, p < 0.001; I2 = 15%). No severe adverse events were reported. Topical use of diquafosol was associated with a higher risk of overall adverse events as compared to HA (odds ratio: 1.71, 95% CI: 1.08 to 2.71, p = 0.02; I2 = 18%). Topical treatment with 3% diquafosol may be more effective than 0.1% HA for patients with DED. However, the long-term efficacy and tolerability of diquafosol still need to be determined.

Does a coaxial double pigtail stent reduce adverse events after lumen apposing metal stent placement for pancreatic fluid collections? A systematic review and meta-analysis.

Lumen apposing metal stents (LAMSs) have a higher clinical success rate for managing pancreatic fluid collections. But they are associated with adverse events (AEs) like bleeding, migration, buried stent, occlusion, and infection. It has been hypothesized that placing a double pigtail stent (DPS) within LAMS may mitigate these AEs. The present systematic review and meta-analysis were conducted to compare the outcome and AEs associated with LAMS with or without a coaxial DPS (LAMS-DPS). A comprehensive literature search of three databases from January 2010 to August 2022 was conducted for studies comparing the outcome and AEs of LAMS alone and LAMS-DPS. Pooled incidence and risk ratios (RRs) with 95% confidence intervals (CIs) were calculated for all the dichotomous outcomes. Overall, eight studies (n = 460) were included in the final analysis. The clinical success rate (RR 1.00, 95% CI: 0.87-1.14) and the risk of overall AEs (RR 1.60, 95% CI: 0.95-2.68) remained comparable between both groups. There was no difference in the risk of bleeding between LAMS alone and LAMS-DPS (RR 1.80, 95% CI: 0.83-3.88). Individual analysis of other AEs, including infection, stent migration, occlusion, and reintervention, showed no difference in the risk between both procedures. The present meta-analysis shows that coaxial DPS within LAMS may not reduce AE rates or improve clinical outcomes. Further larger studies, including patients with walled-off necrosis, are required to demonstrate the benefit of coaxial DPS within LAMS.

Low Testosterone Level and Risk of Adverse Clinical Events among Male Patients with Chronic Kidney Disease: A Systematic Review and Meta-Analysis of Cohort Studies.

The phenomenon of low testosterone level is extremely common in male patients with chronic kidney diseases (CKDs). This meta-analysis aimed to evaluate whether the low circulating testosterone could independently predict adverse outcomes among male patients with chronic kidney diseases (CKDs). The data till May 2022 were systematically searched from Pubmed, Web of Science, and Embase from inception. Studies meeting the PICOS (population, intervention/exposure, control/comparison, outcomes, and study design) principles were included in this meta-analysis. Study-specific effect estimates were pooled using fixed-effects (I2 > 50%) or random-effects models (I2 < 50%). Ultimately, 9 cohort studies covering 5331 patients with CKDs were involved in this meta-analysis. The results suggested that per 1-standard deviation (SD) decrease in total testosterone independently increased the risk of all-cause mortality by 27% [hazard risk (HR) 1.27, 95% confidence interval (CI) 1.16–1.38], cardiovascular mortality by 100% (HR 2.00, 95% CI 1.39–2.86), cardiovascular events by 20% (HR 1.20, 95% CI 1.04–1.39), and infectious events by 41% (HR 1.41, 95% CI 1.08–1.84). Besides, with per 1-SD decrease in free testosterone, the risk of overall adverse events increased by 66% (HR 1.66, 95% CI 1.34–2.05). Stratified analyses indicated that the negative relationship of the total testosterone with all-cause death risk was independent of factors involving age, race, body mass index, diabetes, hypertension, C-reactive protein, creatinine, and sex hormone binding globulin. In conclusion, it was identified that low endogenous testosterone could serve as an independent predictor of adverse clinical events among male patients with CKDs.

Efficacy and Safety of JAK Inhibitors for Rheumatoid Arthritis: A Meta-Analysis.

Background: More and more trials have been conducted. We aimed to assess the efficacy and safety of different JAKinibs in RA. Methods: A systematic search of randomized controlled trials (RCTs) with JAKinib treatment in RA published in the Medline, Embase, and Cochrane databases up to May 2021 was performed. Results: 37 trials involving 15,174 patients were identified. Pooled analysis revealed that JAKinibs were associated with significant therapeutic improvement in RA patients as determined by ACR20 (RR = 2.03, 95% CI: 1.85 to 2.28) and HAQ-DI (MD = −0.31, 95% CI: −0.33 to −0.28) over placebo. Compared to placebo, JAKinib treatment was also associated with more adverse events (RR = 1.10, p < 0.001; RR = 1.29, p < 0.001; RR = 1.59, p = 0.02). Baricitinib and upadacitinib were related to more frequent adverse events (RR = 1.10; 95% CI: 1.01, 1.21; RR = 1.19; 95% CI: 1.11, 1.28) and infection (RR = 1.22; 95% CI: 1.09, 1.37; RR = 1.38; 95% CI: 1.22, 1.56), whereas only baricitinib was associated with more herpes zoster (RR = 3.15; 95% CI: 1.19, 8.33). Conclusions: JAKinibs were superior to placebo for improving signs, symptoms, and health-related quality of life in RA patients at short term, whereas the overall risk of adverse events and infections were greater with baricitinib and upadacitinib, and a higher risk of herpes zoster was only associated with baricitinib. More trials are needed to investigate the long-term safety.

Impact of cytochrome P450 2C19 polymorphisms on the clinical efficacy and safety of voriconazole: an update systematic review and meta-analysis.

To assess the impact of cytochrome P450 (CYP) 2C19 polymorphisms on the clinical efficacy and safety of voriconazole. We systematically searched PubMed, EMBASE, CENTRAL, ClinicalTrials.gov, and three Chinese databases from their inception to 18 March 2021 using a predefined search algorithm to identify relevant studies. Studies that reported voriconazole-treated patients and information on CYP2C19 polymorphisms were included. The efficacy outcome was success rate. The safety outcomes included overall adverse events, hepatotoxicity, and neurotoxicity. A total of 20 studies were included. Intermediate metabolizers (IMs) and poor metabolizers (PMs) were associated with increased success rates compared with normal metabolizers (NMs) [risk ratio (RR), 1.18; 95% confidence interval (CI), 1.03-1.34; I2 = 0%; P = 0.02; RR, 1.28; 95% CI, 1.06-1.54; I2 = 0%; P = 0.01]. PMs were at increased risk of overall adverse events in comparison with NMs and IMs (RR, 2.18; 95% CI, 1.35-3.53; I2 = 0%; P = 0.001; RR, 1.80; 95% CI, 1.23-2.64; I2 = 0%; P = 0.003). PMs demonstrated a trend towards an increased incidence of hepatotoxicity when compared with NMs (RR, 1.60; 95% CI, 0.94-2.74; I2 = 27%; P = 0.08), although there was no statistically significant difference. In addition, there was no significant association between CYP2C19 polymorphisms and neurotoxicity. IMs and PMs were at a significant higher success rate in comparison with NMs. PMs were significantly associated with an increased incidence of all adverse events compared with NMs and IMs. Researches are expected to further confirm these findings. Additionally, the relationship between hepatotoxicity and CYP2C19 polymorphisms deserves clinical attention.

Interventions for treating proximal humeral fractures in adults.

Interventions for treating proximal humeral fractures in adults.

Arthroplasties for hip fracture in adults.

Arthroplasties for hip fracture in adults.

Meta-Analysis of the Efficacy and Safety of Finerenone in Diabetic Kidney Disease

Background: The phase III clinical trial of the nonsteroidal mineralocorticoid receptor antagonist finerenone (BAY 94-8862) has been completed, aiming to investigate renal and cardiovascular outcomes in type 2 diabetes (T2D) with chronic kidney disease (CKD). However, the efficacy and safety of finerenone in renal function remain controversial. The purpose of this study was to explore the efficacy and safety of finerenone in treating the patients with diabetic kidney disease (DKD). Methods: Databases of PubMed, Cochrane Library, Embase, and Web of Science were searched for randomized controlled trials (RCTs) on patients with DKD receiving finerenone treatment from inception to September 2021. Data including patient characteristics and interested outcomes were extracted, and the dichotomous data and continuous variables were evaluated using risk ratio (RR) with 95% confidence intervals (CIs) and mean differences (MD) with 95% CIs, respectively. Results: A total of 4 RCTs involving 13,945 patients were included in this meta-analysis. Analysis results demonstrated that patients receiving finerenone showed a significant decrease in changing urinary albumin-to-creatinine ratio (UACR) from baseline (MD: −0.30; 95% CI [−0.33, −0.27], p = 0.46, I² = 0%) (p < 0.05). The number of patients with ≥40% reduction in estimated glomerular filtration rate (eGFR) from baseline in the finerenone group was significantly smaller than that in the placebo group (RR: 0.85; 95% CI [0.78, 0.93], p = 0.60, I² = 0%) (p < 0.05). No difference was found in adverse events between the finerenone and placebo groups (RR: 1.00; 95% CI [0.98, 1.01], p = 0.94, I² = 0%) (p = 0.65). The incidence of hyperkalemia was higher in the finerenone group than that in the placebo group (RR: 2.03; 95% CI [1.83, 2.26], p = 0.95, I² = 0%) (p < 0.05). Conclusion: Finerenone contributes to the reduction of UACR and can ameliorate the deterioration of renal function in patients with T2D and CKD. The higher risk of hyperkalemia was found in the finerenone group compared with placebo; however, there was no difference in the risk of overall adverse events.

Effect of sodium-glucose cotransporter-2 inhibitors on patients with essential hypertension and pre-hypertension: a meta-analysis.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors are novel, hypoglycemic drugs exhibiting cardiovascular protective activities. If SGLT2 inhibitors can be successfully used as antihypertensive drugs, they can be administered to patients with both hypertension and type 2 diabetes, thus diminishing the risk of polypharmacy-related complications. The aim of this review was to evaluate the hypotensive efficacy of SGLT2 inhibitors in patients with hypertension and pre-hypertension. We systematically searched PubMed, Embase, and Cochrane for randomized controlled trials comparing SGLT2 inhibitors and a placebo in patients with essential hypertension and pre-hypertension. Our main outcome was the mean change in office blood pressure (BP) and body weight. We assessed the pooled data using a fixed-effects model. After screening 968 articles, nine trials were eligible (n = 2450 participants). Compared to the mean changes in systolic and diastolic BP in patients who were given a placebo, those in patients who used SGLT2 inhibitors were -5.04 mmHg and -1.67 mmHg, respectively. An intensive dose of SGLT2 inhibitors resulted in a stronger BP-lowering effect than the regular dose. Compared to that in the placebo group, the mean change in mean body weight was -1.74 kg in the SGLT2 inhibitor group. There was no significant difference between the two groups regarding the risk of overall adverse events. The pooled effect estimates remained similar across all residual studies and their subgroups in the leave-one-out sensitivity analysis. SGLT2 inhibitors had a statistically significant BP-lowering effect on hypertension and pre-hypertension, which was further enhanced with increased drug dosage. SGLT2 inhibitors have the potential to be used as antihypertensive agents in patients with hypertension complicated by type 2 diabetes.

Cesarean delivery on maternal request in the United States from 1999 to 2015

The rate of cesarean delivery has increased in the United States over the last several decades. However, the rate of cesarean delivery on maternal request remains undetermined, and recent data on cesarean delivery on maternal request are lacking. This study aimed to describe the prevalence and temporal trends of cesarean delivery on maternal request in the United States and characterize the population of women who elect to undergo a cesarean delivery in the absence of fetal or maternal indications. Maternal outcomes between women who delivered by cesarean delivery on maternal request and those who did not were compared. A retrospective cohort study was conducted using data from the Healthcare Cost and Utilization Project-Nationwide Inpatient Sample from 1999 to 2015. An algorithm based on International Classification of Diseases, Ninth Revision codes was created to identify patients who underwent a primary elective cesarean delivery in the absence of fetal or maternal indications. Maternal characteristics and outcomes between women who delivered by cesarean delivery on maternal request and those who did not were compared using descriptive and logistic regression analyses. Of the 13,698,835 deliveries included throughout the study period, 228,586 were identified as cesarean delivery on maternal request. Rates of cesarean delivery on maternal request among all live births increased throughout the study period, from 1% in 1999 to 1.62% in 2015 (P<.0001). Women who delivered by cesarean delivery on maternal request were more likely to be >35 years of age, were in the highest income quartile, and have private insurance. Cesarean delivery on maternal request was associated with an increased risk of venous thromboembolism (odds ratio, 1.9; 95% confidence interval, 1.8-2.0), myocardial infarction (odds ratio, 6.3; 95% confidence interval, 3.8-10.4), sepsis (odds ratio, 5.6; 95% confidence interval, 4.7-6.6), disseminated intravascular coagulation (odds ratio, 2.9; 95% confidence interval, 2.3-3.7), death (odds ratio, 14.5; 95% confidence interval, 11.4-18.6), and prolonged hospital stay (odds ratio, 4.9; 95% confidence interval, 4.8-5.1) and a lower risk of postpartum hemorrhage (odds ratio, 0.7; 95% confidence interval, 0.7-0.7). Our findings indicated that cesarean delivery on maternal request accounts for a small but increasing proportion of all cesarean deliveries in the United States. Cesarean delivery on maternal request was more prevalent among women with certain demographic characteristics, indicating that the option of cesarean delivery on maternal request may be more appealing or more frequently offered to a certain population of women. Although the overall risk of adverse events is low for individual births, population effects can result in increased morbidity and mortality. Therefore, the rates of cesarean delivery on maternal request should be monitored on a national level. Study findings were limited by the absence of a specific diagnostic code for cesarean delivery on maternal request.

Efficacy and Safety of COVID-19 Vaccines in Phase III Trials: A Meta-Analysis.

Nowadays, the vaccination with COVID-19 vaccines is being promoted worldwide, professionals and common people are very concerned about the efficacy and safety of COVID-19 vaccines. No published systematic review and meta-analysis has assessed the efficacy and safety of the COVID-19 vaccines based on data from phase III clinical trials. Therefore, this study has estimated the efficacy and safety of COVID-19 vaccines and the differences between vaccine types. PubMed, Embase, the Cochrane Library, CNKI, Wanfang, medRxiv databases and two websites were used to retrieve the studies. Random-effects models were used to estimate the pooled efficacy and safety with risk ratio (RR). A total of eight studies, seven COVID-19 vaccines and 158,204 subjects were included in the meta-analysis. All the vaccines had a good preventive effect on COVID-19 (RR = 0.17, 95% CI: 0.09–0.32), and the mRNA vaccine (RR = 0.05, 95% CI: 0.03–0.09) was the most effective against COVID-19, while the inactivated vaccine (RR = 0.32, 95% CI: 0.19–0.54) was the least. In terms of safety, the risk of overall adverse events showed an increase in the vaccine group after the first (RR = 1.46, 95% CI: 1.03–2.05) or second (RR = 1.52, 95% CI: 1.04–2.20) injection. However, compared with the first injection, the risk of local (RR = 2.64, 95% CI: 1.02–6.83 vs. RR = 2.25, 95% CI: 0.52–9.75) and systemic (RR = 1.33, 95% CI: 1.21–1.46 vs. RR = 1.59, 95% CI: 0.84–3.01) adverse events decreased after the second injection. As for the mRNA vaccine, the risk of overall adverse events increased significantly, compared with the placebo, no matter whether it was the first (RR = 1.83, 95% CI = 1.80–1.86) or the second (RR = 2.16, 95% CI = 2.11–2.20) injection. All the COVID-19 vaccines that have published the data of phase III clinical trials have excellent efficacy, and the risk of adverse events is acceptable. The mRNA vaccines were the most effective against COVID-19, meanwhile the risk and grade of adverse events was minimal, compared to that of severe symptoms induced by COVID-19.

Association of advanced age with intubation-related adverse events in the emergency department: a multicentre prospective observational study

BackgroundWhile the older population accounts for an increasing proportion of emergency department (ED), little is known about intubation-related adverse events in this high-risk population. We sought to determine whether advanced...