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Nutrition Reviews Jul 2023Iron deficiency and anemia have serious consequences, especially for children and pregnant women. Iron salts are commonly provided as oral supplements to prevent and... (Meta-Analysis)
Meta-Analysis
The effects of oral ferrous bisglycinate supplementation on hemoglobin and ferritin concentrations in adults and children: a systematic review and meta-analysis of randomized controlled trials.
CONTEXT
Iron deficiency and anemia have serious consequences, especially for children and pregnant women. Iron salts are commonly provided as oral supplements to prevent and treat iron deficiency, despite poor bioavailability and frequently reported adverse side effects. Ferrous bisglycinate is a novel amino acid iron chelate that is thought to be more bioavailable and associated with fewer gastrointestinal (GI) adverse events as compared with iron salts.
OBJECTIVE
A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to evaluate the effects of ferrous bisglycinate supplementation compared with other iron supplements on hemoglobin and ferritin concentrations and GI adverse events.
DATA SOURCES
A systematic search of electronic databases and grey literature was performed up to July 17, 2020, yielding 17 RCTs that reported hemoglobin or ferritin concentrations following at least 4 weeks' supplementation of ferrous bisglycinate compared with other iron supplements in any dose or frequency.
DATA EXTRACTION
Random-effects meta-analyses were conducted among trials of pregnant women (n = 9) and children (n = 4); pooled estimates were expressed as standardized mean differences (SMDs). Incidence rate ratios (IRRs) were estimated for GI adverse events, using Poisson generalized linear mixed-effects models. The remaining trials in other populations (n = 4; men and nonpregnant women) were qualitatively evaluated.
DATA ANALYSIS
Compared with other iron supplements, supplementation with ferrous bisglycinate for 4-20 weeks resulted in higher hemoglobin concentrations in pregnant women (SMD, 0.54 g/dL; 95% confidence interval [CI], 0.15-0.94; P < 0.01) and fewer reported GI adverse events (IRR, 0.36; 95%CI, 0.17-0.76; P < 0.01). We observed a non-significant trend for higher ferritin concentrations in pregnant women supplemented with ferrous bisglycinate. No significant differences in hemoglobin or ferritin concentrations were detected among children.
CONCLUSION
Ferrous bisglycinate shows some benefit over other iron supplements in increasing hemoglobin concentration and reducing GI adverse events among pregnant women. More trials are needed to assess the efficacy of ferrous bisglycinate against other iron supplements in other populations.
PROSPERO REGISTRATION NO
CRD42020196984.
Topics: Adult; Child; Female; Humans; Male; Pregnancy; Anemia, Iron-Deficiency; Dietary Supplements; Ferritins; Hemoglobins; Iron; Iron Deficiencies; Randomized Controlled Trials as Topic; Salts; Ferrous Compounds
PubMed: 36728680
DOI: 10.1093/nutrit/nuac106 -
JAMA Oct 2023The effect of continuous positive airway pressure (CPAP) on secondary cardiovascular disease prevention is highly debated. (Meta-Analysis)
Meta-Analysis
IMPORTANCE
The effect of continuous positive airway pressure (CPAP) on secondary cardiovascular disease prevention is highly debated.
OBJECTIVE
To assess the effect of CPAP treatment for obstructive sleep apnea (OSA) on the risk of adverse cardiovascular events in randomized clinical trials.
DATA SOURCES
PubMed (MEDLINE), EMBASE, Current Controlled Trials: metaRegister of Controlled Trials, ISRCTN Registry, European Union clinical trials database, CENTRAL (Cochrane Central Register of Controlled Trials), and ClinicalTrials.gov databases were systematically searched through June 22, 2023.
STUDY SELECTION
For qualitative and individual participant data (IPD) meta-analysis, randomized clinical trials addressing the therapeutic effect of CPAP on cardiovascular outcomes and mortality in adults with cardiovascular disease and OSA were included.
DATA EXTRACTION AND SYNTHESIS
Two reviewers independently screened records, evaluated potentially eligible primary studies in full text, extracted data, and cross-checked errors. IPD were requested from authors of the selected studies (SAVE [NCT00738179], ISAACC [NCT01335087], and RICCADSA [NCT00519597]).
MAIN OUTCOMES AND MEASURES
One-stage and 2-stage IPD meta-analyses were completed to estimate the effect of CPAP treatment on risk of recurrent major adverse cardiac and cerebrovascular events (MACCEs) using mixed-effect Cox regression models. Additionally, an on-treatment analysis with marginal structural Cox models using inverse probability of treatment weighting was fitted to assess the effect of good adherence to CPAP (≥4 hours per day).
RESULTS
A total of 4186 individual participants were evaluated (82.1% men; mean [SD] body mass index, 28.9 [4.5]; mean [SD] age, 61.2 [8.7] years; mean [SD] apnea-hypopnea index, 31.2 [17] events per hour; 71% with hypertension; 50.1% receiving CPAP [mean {SD} adherence, 3.1 {2.4} hours per day]; 49.9% not receiving CPAP [usual care], mean [SD] follow-up, 3.25 [1.8] years). The main outcome was defined as the first MACCE, which was similar for the CPAP and no CPAP groups (hazard ratio, 1.01 [95% CI, 0.87-1.17]). However, an on-treatment analysis by marginal structural model revealed a reduced risk of MACCEs associated with good adherence to CPAP (hazard ratio, 0.69 [95% CI, 0.52-0.92]).
CONCLUSIONS AND RELEVANCE
Adherence to CPAP was associated with a reduced MACCE recurrence risk, suggesting that treatment adherence is a key factor in secondary cardiovascular prevention in patients with OSA.
Topics: Female; Humans; Male; Middle Aged; Cardiovascular Diseases; Continuous Positive Airway Pressure; Hypertension; Proportional Hazards Models; Sleep Apnea, Obstructive; Risk; Aged; Secondary Prevention; Patient Compliance
PubMed: 37787793
DOI: 10.1001/jama.2023.17465 -
Clinical Breast Cancer Dec 2023Trastuzumab deruxtecan (T-DXd) is a novel antibody-drug-conjugate (ADC), primarily used in the treatment of HER2-positive breast cancer. This study aimed to conduct a... (Meta-Analysis)
Meta-Analysis Review
Trastuzumab deruxtecan (T-DXd) is a novel antibody-drug-conjugate (ADC), primarily used in the treatment of HER2-positive breast cancer. This study aimed to conduct a systematic review to evaluate the efficacy and safety of T-DXd in treating breast cancer, based on clinical trials. A systematic search of the literature was conducted to identify clinical trials investigating the efficacy and safety of T-DXd in breast cancer. Clinical trials of any phase were included. Outcome measures were any adverse events and survival. Meta-analysis was conducted where possible. Pooled prevalence for each adverse event of any grade and grade 3 or greater were estimated. Progression-free survival (PFS), overall survival (OS) and objective response rates (ORRs) were also reported to evaluate the efficacy of T-DXd in breast cancer. A total of 1593 patients from 6 clinical trials were included. Common adverse events of any grade were nausea, anemia, neutropenia, vomiting, fatigue, constipation and diarrhea, occurring in greater than 30% of cases. In terms of adverse events of grade 3 or more, only anemia and neutropenia occurred at a relatively high rate. Median PFS ranged from 11.1 to 22.1 months. There was evidence of a benefit of T-DXd compared to controls in terms of both PFS (OR: 0.38; 95% CI: 0.32, 0.45) and OS (OR: 0.61; 95% CI: 0.48, 0.78). ORRs ranged from 37% to 79.9%. The present systematic review shows evidence that T-DXd is a safe and effective agent in the treatment of breast cancer based on currently available data. The most common adverse events affected the blood, lymphatic and gastrointestinal systems. Interstitial lung disease (ILD) is a notable and potentially serious adverse event.
Topics: Humans; Female; Breast Neoplasms; Trastuzumab; Camptothecin; Neutropenia; Anemia; Receptor, ErbB-2
PubMed: 37775347
DOI: 10.1016/j.clbc.2023.09.005 -
Safety and Efficacy of Long-Acting Injectable Agents for HIV-1: Systematic Review and Meta-Analysis.JMIR Public Health and Surveillance Jul 2023HIV-1 infection continues to affect global health. Although antiretrovirals can reduce the viral load or prevent HIV-1 infection, current drugs require daily oral use... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
HIV-1 infection continues to affect global health. Although antiretrovirals can reduce the viral load or prevent HIV-1 infection, current drugs require daily oral use with a high adherence level. Long-acting antiretrovirals (LA-ARVs) significantly improve medication adherence and are essential for HIV-1 prophylaxis and therapy.
OBJECTIVE
This study aimed to investigate the safety and efficacy of long-acting cabotegravir (CAB-LA) and long-acting rilpivirine (RPV-LA) in the prevention and treatment of HIV-1 infection.
METHODS
PubMed, Embase, and the Cochrane Library were searched for studies from database inception to November 12, 2022. We included studies that reported efficacy and safety data on LA-ARV intervention in people living with HIV and excluded reviews, animal studies, and articles with missing or duplicate data. Virological suppression was defined as plasma viral load <50 copies/mL 6 months after antiviral therapy initiation. We extracted outcomes for analysis and expressed dichotomous data as risk ratios (RRs) and continuous data as mean differences. Depending on the heterogeneity assessment, a fixed- or random-effects model was used for data synthesis. We performed subgroup analyses of the partial safety and efficacy outcomes of CAB-LA+RPV-LA. The protocol was registered with the Open Science Framework.
RESULTS
We included 12 trials comprising 10,957 individuals, of which 7 were prevention trials and 5 were treatment trials. CAB-LA and RPV-LA demonstrated safety profiles comparable with those of the placebo in terms of adverse event-related withdrawal. Moreover, the efficacy data showed that CAB-LA had a better effect on HIV-1 prevention than tenofovir disoproxil fumarate-emtricitabine (17/5161, 0.33% vs 75/5129, 1.46%; RR 0.21, 95% CI 0.07-0.61; I=70%). Although CAB-LA+RPV-LA had more drug-related adverse events (556/681, 81.6% vs 37/598, 6.2%; RR 12.50, 95% CI 3.98-39.23; I=85%), a mild or moderate injection site reaction was the most common reaction, and its frequency decreased over time. The efficacy of CAB-LA+RPV-LA was comparable with that of daily oral drugs at 48 and 96 weeks (1302/1424, 91.43% vs 915/993, 92.2%; RR 0.99, 95% CI 0.97-1.02; I=0%), and a high level of virological suppression of 80.9% (186/230) was maintained even after 5 years of LA-ARV use. Similar efficacy outcomes were observed in both treatment-naive and treatment-experienced patients (849/911, 93.2% vs 615/654, 94%; RR 0.99, 95% CI 0.96-1.02; I=0%). According to the questionnaires, more than 85% of people living with HIV favored LA-ARVs.
CONCLUSIONS
LA-ARVs showed favorable safety profiles for both the prevention and treatment of HIV-1 infection and were well tolerated. CAB-LA has more satisfactory efficacy than tenofovir disoproxil fumarate-emtricitabine, significantly reducing the rate of HIV-1 infection. CAB-LA+RPV-LA maintains virological suppression for a long time and may be a viable switching strategy with enhanced public health benefits by reducing transmission. However, further trials are required to confirm the efficacy of these drugs.
Topics: Humans; Anti-HIV Agents; Emtricitabine; HIV Infections; HIV-1; Tenofovir
PubMed: 37498645
DOI: 10.2196/46767 -
Frontiers in Medicine 2023The effects of early mobilization (EM) on intensive care unit (ICU) patients remain unclear. A meta-analysis of randomized controlled trials was performed to evaluate... (Review)
Review
BACKGROUND
The effects of early mobilization (EM) on intensive care unit (ICU) patients remain unclear. A meta-analysis of randomized controlled trials was performed to evaluate its effect in mechanically ventilated adult ICU patients.
METHODS
We searched randomized controlled trials (RCTs) published in Medline, Embase, and CENTRAL databases (from inception to November 2022). According to the difference in timing and type, the intervention group was defined as a systematic EM group, and comparator groups were divided into the late mobilization group and the standard EM group. The primary outcome was mortality. The secondary outcomes were ICU length of stay, duration of mechanical ventilation (MV), and adverse events. EM had no impact on 180-day mortality and hospital mortality between intervention groups and comparator groups (RR 1.09, 95% CI 0.89-1.33, = 0.39). Systemic EM reduced the ICU length of stay (LOS) (MD -2.18, 95% CI -4.22--0.13, = 0.04) and the duration of MV (MD -2.27, 95% CI -3.99--0.56, = 0.009), but it may increase the incidence of adverse events in patients compared with the standard EM group (RR 1.99, 95% CI 1.25-3.16, = 0.004).
CONCLUSION
Systematic EM has no significant effect on short- or long-term mortality in mechanically ventilated adult ICU patients, but systematic EM could reduce the ICU LOS and duration of MV.
PubMed: 37448799
DOI: 10.3389/fmed.2023.1202754 -
Medicine Oct 2023Biological agents are commonly used for the first-line treatment of ulcerative colitis (UC). However, small-molecule drugs and microbiome therapies are now being used as... (Meta-Analysis)
Meta-Analysis
Comparative of the effectiveness and safety of biological agents, small molecule drugs, and microbiome therapies in ulcerative colitis: Systematic review and network meta-analysis.
BACKGROUND
Biological agents are commonly used for the first-line treatment of ulcerative colitis (UC). However, small-molecule drugs and microbiome therapies are now being used as new treatments for ulcerative colitis. We aimed to compare the relative efficacy and safety of biologics, small-molecule drugs, and microbiome therapies for the treatment of patients with moderate-to-severe ulcerative colitis.
METHODS
We searched the Cochrane, Embase, and PubMed databases from their inception to December 2022. RCTs that recruited patients with moderate-to-severe ulcerative colitis treated with biological agents, small-molecule drugs, and microbiome therapies. Efficacy outcomes were induction of clinical remission and mucosal healing; safety outcomes were adverse events and serious adverse events. A network meta-analysis with multivariate consistency model random-effect meta-regression was done, with rankings based on surface under the cumulative ranking curve (SUCRA) values. Higher SUCRA scores correlate with better efficacy, whereas lower SUCRA scores correlate with better safety.
RESULTS
A total of 31 RCTs comprising 7933 UC patients were included in our studies. A risk of bias assessment showed a low risk of bias for most of the included studies. Upadacitinib ranked highest for induction of clinical remission (SUCRA, 0.83) and mucosal healing (SUCRA, 0.44). Moreover, no treatments were found to increase the occurrence of adverse events compared with placebos. Ustekinumab ranked lowest for adverse events (SUCRA 0.26) and probiotic ranked lowest for serious adverse events (0·21), whereas tofacitinib ranked highest for adverse events (0·43) and upadacitinib ranked highest for serious adverse events (0·43).
CONCLUSION
In this systematic review and network meta-analysis, we found upadacitinib to be ranked highest for the induction of clinical remission and mucosal healing, but the worst performing agent in terms of adverse events in UC patients. Probiotics were the best-performing agent for safety outcomes. More trials of direct comparisons are needed to inform clinical decision-making with greater confidence.
Topics: Humans; Biological Factors; Colitis, Ulcerative; Network Meta-Analysis; Ustekinumab; Biological Products
PubMed: 37904440
DOI: 10.1097/MD.0000000000035689 -
JAMA Oncology May 2024To date, no meta-analyses have comprehensively assessed the association of neoadjuvant chemoimmunotherapy with clinical outcomes in non-small cell lung cancer (NSCLC) in... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
To date, no meta-analyses have comprehensively assessed the association of neoadjuvant chemoimmunotherapy with clinical outcomes in non-small cell lung cancer (NSCLC) in randomized and nonrandomized settings. In addition, there exists controversy concerning the efficacy of neoadjuvant chemoimmunotherapy for patients with NSCLC with programmed cell death 1 ligand 1 (PD-L1) levels less than 1%.
OBJECTIVE
To compare neoadjuvant chemoimmunotherapy with chemotherapy by adverse events and surgical, pathological, and efficacy outcomes using recently published randomized clinical trials and nonrandomized trials.
DATA SOURCES
MEDLINE and Embase were systematically searched from January 1, 2013, to October 25, 2023, for all clinical trials of neoadjuvant chemoimmunotherapy and chemotherapy that included at least 10 patients.
STUDY SELECTION
Observational studies and trials reporting the use of neoadjuvant radiotherapy, including chemoradiotherapy, molecular targeted therapy, or immunotherapy monotherapy, were excluded.
MAIN OUTCOMES AND MEASURES
Surgical, pathological, and efficacy end points and adverse events were pooled using a random-effects meta-analysis.
RESULTS
Among 43 eligible trials comprising 5431 patients (4020 males [74.0%]; median age range, 55-70 years), there were 8 randomized clinical trials with 3387 patients. For randomized clinical trials, pooled overall survival (hazard ratio, 0.65; 95% CI, 0.54-0.79; I2 = 0%), event-free survival (hazard ratio, 0.59; 95% CI, 0.52-0.67; I2 = 14.9%), major pathological response (risk ratio, 3.42; 95% CI, 2.83-4.15; I2 = 31.2%), and complete pathological response (risk ratio, 5.52; 95% CI, 4.25-7.15; I2 = 27.4%) favored neoadjuvant chemoimmunotherapy over neoadjuvant chemotherapy. For patients with baseline tumor PD-L1 levels less than 1%, there was a significant benefit in event-free survival for neoadjuvant chemoimmunotherapy compared with chemotherapy (hazard ratio, 0.74; 95% CI, 0.62-0.89; I2 = 0%).
CONCLUSION AND RELEVANCE
This study found that neoadjuvant chemoimmunotherapy was superior to neoadjuvant chemotherapy across surgical, pathological, and efficacy outcomes. These findings suggest that patients with resectable NSCLC with tumor PD-L1 levels less than 1% may have an event-free survival benefit with neoadjuvant chemoimmunotherapy.
Topics: Aged; Humans; Middle Aged; Carcinoma, Non-Small-Cell Lung; Immunotherapy; Lung Neoplasms; Neoadjuvant Therapy; Treatment Outcome
PubMed: 38512301
DOI: 10.1001/jamaoncol.2024.0057 -
International Journal of Oral and... Jan 2024Clinicians frequently prescribe systemic antibiotics after lower third molar extractions to prevent complications such as surgical site infections and dry socket. A... (Meta-Analysis)
Meta-Analysis Review
Clinicians frequently prescribe systemic antibiotics after lower third molar extractions to prevent complications such as surgical site infections and dry socket. A systematic review of randomised clinical trials was conducted to compare the risk of dry socket and surgical site infection after the removal of lower third molars with different prophylactic antibiotics. The occurrence of any antibiotic-related adverse event was also analysed. A pairwise and network meta-analysis was performed to establish direct and indirect comparisons of each outcome variable. Sixteen articles involving 2158 patients (2428 lower third molars) were included, and the following antibiotics were analysed: amoxicillin (with and without clavulanic acid), metronidazole, azithromycin, and clindamycin. Pooled results favoured the use of antibiotics to reduce dry socket and surgical site infection after the removal of a lower third molar, with a number needed to treat of 25 and 18, respectively. Although antibiotic prophylaxis was found to significantly reduce the risk of dry socket and surgical site infection in patients undergoing lower third molar extraction, the number of patients needed to treat was high. Thus, clinicians should evaluate the need to prescribe antibiotics taking into consideration the patient's systemic status and the individual risk of developing a postoperative infection.
Topics: Humans; Dry Socket; Antibiotic Prophylaxis; Surgical Wound Infection; Molar, Third; Network Meta-Analysis; Anti-Bacterial Agents; Tooth Extraction
PubMed: 37612199
DOI: 10.1016/j.ijom.2023.08.001 -
Renal Failure Dec 2023Belimumab is the first biological agent approved for the treatment of systemic lupus erythematosus (SLE), but the efficacy of belimumab for lupus nephritis (LN) is not... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Belimumab is the first biological agent approved for the treatment of systemic lupus erythematosus (SLE), but the efficacy of belimumab for lupus nephritis (LN) is not clear. We conducted this meta-analysis and systematic review to compare the efficacy and safety of belimumab with those of conventional therapy for LN.
METHODS
PubMed, EMBASE, Cochrane Library, Clinical Trials.gov were searched in 31 December 2022 to identify relevant adult human studies reporting effectiveness outcomes of belimumab in patients with LN. Review manager (RevMan 5.4) was used for data analysis with fixed effects model based on heterogeneities.
RESULTS
Six randomized controlled trials (RCTs) were included in the quantitative analysis. A total of 2960 participants were identified. Belimumab plus standard therapy significantly improved total renal response rates (RR, 1.31; 95% CI, 1.11-1.53; = 0.001) and complete renal RRs (1.47; 95% CI, 1.07-2.02; = 0.02) compared with the control plus standard therapy group. It significantly reduced the risk of renal flare (RR, 0.51; 95% CI, 0.37-0.69; < 0.001) and renal function worsening or progression to end-stage renal disease (ESRD) (RR, 0.56; 95% CI, 0.40-0.79; = 0.001). When assessed with the incidence of adverse events, no significant differences between the two groups were observed for the occurrence of treatment-related adverse events (RR, 1.04; 95% CI, 0.99-1.09; = 0.12).
CONCLUSIONS
This meta-analysis showed that belimumab plus standard therapy was more effective and had a favorable safety in patients with LN.
Topics: Adult; Humans; Lupus Nephritis; Lupus Erythematosus, Systemic; Antibodies, Monoclonal, Humanized; Kidney; Treatment Outcome; Immunosuppressive Agents
PubMed: 37194710
DOI: 10.1080/0886022X.2023.2207671 -
JAMA Oct 2023Gefapixant represents an emerging therapy for patients with refractory or unexplained chronic cough. (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Gefapixant represents an emerging therapy for patients with refractory or unexplained chronic cough.
OBJECTIVE
To evaluate the efficacy and tolerability of gefapixant for the treatment of adults with refractory or unexplained chronic cough.
DATA SOURCES
MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Web of Science from November 2014 to July 2023.
STUDY SELECTION
Two reviewers independently screened for parallel and crossover randomized clinical trials (RCTs) that compared, in patients with refractory or unexplained chronic cough, either gefapixant with placebo, or 2 or more doses of gefapixant with or without placebo.
DATA EXTRACTION AND SYNTHESIS
Two reviewers independently extracted data. A frequentist random-effects dose-response meta-analysis or pairwise meta-analysis was used for each outcome. The GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach was used to rate the certainty in whether patients would perceive the effects as important (greater than the minimal important difference [MID]) or small (less than the MID).
MAIN OUTCOMES AND MEASURES
Cough frequency (measured using the VitaloJAK cough monitor; MID, 20%), cough severity (measured using the 100-mm visual analog scale [VAS]; higher score is worse; MID, 30 mm), cough-specific quality of life (measured using the Leicester Cough Questionnaire [LCQ]; score range, 3 [maximal impairment] to 21 [no impairment]; MID, 1.3 points), treatment-related adverse events, adverse events leading to discontinuation, and taste-related adverse events.
RESULTS
Nine RCTs including 2980 patients were included in the primary analysis. Compared with placebo, gefapixant (45 mg twice daily) had small effects on awake cough frequency (17.6% reduction [95% CI, 10.6%-24.0%], moderate certainty), cough severity on the 100-mm VAS (mean difference, -6.2 mm [95% CI, -4.1 to -8.4]; high certainty), and cough-specific quality of life on the LCQ (mean difference, 1.0 points [95% CI, 0.7-1.4]; moderate certainty). Compared with placebo, gefapixant (45 mg twice daily) probably caused an important increase in treatment-related adverse events (32 more per 100 patients [95% CI, 13-64 more], moderate certainty) and taste-related adverse events (32 more per 100 patients [95% CI, 22-46 more], high certainty). High-certainty evidence suggests that gefapixant (15 mg twice daily) had small effects on taste-related adverse events (6 more per 100 patients [95% CI, 5-8 more]).
CONCLUSIONS AND RELEVANCE
Compared with placebo, gefapixant (45 mg orally twice daily) led to modest improvements in cough frequency, cough severity, and cough-specific quality of life but increased taste-related adverse events.
Topics: Adult; Humans; Cough; Pyrimidines; Quality of Life; Sulfonamides; Dose-Response Relationship, Drug; Treatment Outcome; Chronic Disease; Taste
PubMed: 37694849
DOI: 10.1001/jama.2023.18035