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Cureus Jul 2023Colostrum from mothers is rich in immunomodulating bio-factors such as immunoglobulins (IgA), lactoferrin, and oligosaccharides and supports gut microbial and... (Review)
Review
Colostrum from mothers is rich in immunomodulating bio-factors such as immunoglobulins (IgA), lactoferrin, and oligosaccharides and supports gut microbial and inflammatory processes. The support in these processes may provide some relief for infants who are born pre-term. Pre-term infants are more likely to develop necrotizing enterocolitis (NEC), late-onset sepsis (LOS), and ventilator-acquired/associated pneumonia (VAP). Due to the components of colostrum, there may be incentives towards early administration for preterm infants. An extensive literature review was done using ProQuest, ScienceDirect, and PubMed. Only meta-analyses and experimental studies were used. The search included the keywords 'colostrum and preterm' and 'colostrum and necrotizing enterocolitis'. The initial search generated 13,543 articles and was narrowed to 25 articles through comprehensive inclusion and exclusion criteria. There were significantly higher levels of and in pre-term infants given colostrum and a decrease in and . Salivary secretory IgA increased following oral colostrum administration in pre-term infants along with downregulation of interleukin (IL)-1b and IL-8. It was also observed that tumor necrosis factor (TNF)-a, and interferon-gamma (IFN-g) were significantly higher in the control group. There was no significant difference in the incidence of LOS, NEC, or VAP between pre-term infants receiving colostrum and those who did not. Secondary outcomes such as time to full enteral feeding were improved in pre-term infants receiving oral colostrum in addition to reduced hospital stays. Lastly, there was no difference in mortality between pre-term infants that received colostrum compared to those who did not.
PubMed: 37593258
DOI: 10.7759/cureus.42021 -
Science Progress 2021All cancers can increase the risk of developing venous thromboembolism (VTE), and anticoagulants should be considered as an optimal treatment for patients suffering from... (Meta-Analysis)
Meta-Analysis
All cancers can increase the risk of developing venous thromboembolism (VTE), and anticoagulants should be considered as an optimal treatment for patients suffering from cancer-associated VTE. However, there is still a debate about whether the new oral anticoagulant, rivaroxaban, can bring better efficacy and safety outcomes globally. Thus, this systematic review and meta-analysis was conducted to evaluate the efficacy and safety of rivaroxaban. We searched PubMed, Cochrane Central Register of Controlled Trials, Web of Science, and China National Knowledge Infrastructure for relevant published papers before 1 September 2019, with no language restrictions. The primary outcomes are defined as the recurrence of VTE. The secondary outcomes are defined as clinically relevant non-major bleeding, adverse major bleeding events, and all-cause of death. The data were analyzed by Stata with risk ratio (RR) and 95% confidence interval (CI). Four trials encompassing 1996 patients were included. Rivaroxaban reduced recurrent VTE with no significant difference (RR = 0.68, 95% CI = 0.43-1.07). Similarly, there were no significant differences in adverse major bleeding events (RR = 0.86, 95% CI = 0.37-2.00), clinically relevant non-major bleeding (RR = 1.24, 95% CI = 0.73-2.12) and all-cause mortality (RR = 0.76, 95% CI = 0.40-1.44). In a selected study population of cancer patients with VTE, rivaroxaban is as good as other anticoagulants. Further, carefully designed randomized controlled trials should be performed to confirm these results.
Topics: Administration, Oral; Anticoagulants; Hemorrhage; Humans; Neoplasms; Rivaroxaban; Venous Thromboembolism
PubMed: 33913387
DOI: 10.1177/00368504211012160 -
European Neuropsychopharmacology : the... Jun 2024Long-acting injectable antipsychotics (LAIs) are primarily used for relapse prevention, but in some settings and situations, they may also be useful for acute treatment... (Meta-Analysis)
Meta-Analysis Review
Long-acting injectable antipsychotics (LAIs) are primarily used for relapse prevention, but in some settings and situations, they may also be useful for acute treatment of schizophrenia. We conducted a systematic review and frequentist network meta-analysis of randomized-controlled trials (RCTs), focusing on adult patients in the acute phase of schizophrenia. Interventions were risperidone, paliperidone, aripiprazole, olanzapine, and placebo, administered either orally or as LAI. We synthesized data on overall symptoms, complemented by 17 other efficacy and tolerability outcomes. Confidence in the evidence was assessed with the Confidence-in-Network-Meta-Analysis-framework (CINeMA). We included 115 RCTs with 25,550 participants. All drugs were significantly more efficacious than placebo with the following standardized mean differences and their 95 % confidence intervals: olanzapine LAI -0.66 [-1.00; -0.33], risperidone LAI -0.59[-0.73;-0.46], olanzapine oral -0.55[-0.62;-0.48], aripiprazole LAI -0.54[-0.71; -0.37], risperidone oral -0.48[-0.55;-0.41], paliperidone oral -0.47[-0.58;-0.37], paliperidone LAI -0.45[-0.57;-0.33], aripiprazole oral -0.40[-0.50; -0.31]. There were no significant efficacy differences between LAIs and oral formulations. Sensitivity analyses of the primary outcome overall symptoms largely confirmed these findings. Moreover, some side effects were less frequent under LAIs than under their oral counterparts. Confidence in the evidence was moderate for most comparisons. LAIs are efficacious for acute schizophrenia and may have some benefits compared to oral formulations in terms of side effects. These findings assist clinicians with insights to weigh the risks and benefits between oral and injectable agents when treating patients in the acute phase.
Topics: Humans; Antipsychotic Agents; Administration, Oral; Schizophrenia; Delayed-Action Preparations; Network Meta-Analysis; Randomized Controlled Trials as Topic; Injections; Treatment Outcome
PubMed: 38490016
DOI: 10.1016/j.euroneuro.2024.03.003 -
Alimentary Pharmacology & Therapeutics Oct 2023Ulcerative proctitis (UP) is a common highly symptomatic form of ulcerative colitis that can be difficult to treat. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Ulcerative proctitis (UP) is a common highly symptomatic form of ulcerative colitis that can be difficult to treat.
AIM
To assess the efficacy of medical treatments for UP.
METHODS
We searched MEDLINE, EMBASE, and CENTRAL on 23 November 2022 for randomised controlled trials (RCTs) of medical therapy for adults with UP. Primary outcomes included induction and maintenance of clinical remission. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated for each outcome.
RESULTS
We included 53 RCTs (n = 4096) including 46 induction studies (n = 3731) and seven maintenance studies (n = 365). First-line therapies included topical 5-aminosalicylic acid (5-ASA), conventional corticosteroids, budesonide, and oral 5-ASA. Therapy for refractory UP included topical tacrolimus and small molecules. Topical 5-ASA was superior to placebo for induction (RR 2.72, 95% CI 1.94-3.82) and maintenance of remission (RR 2.09, 95% CI 1.26-3.46). Topical corticosteroids were superior to placebo for induction of remission (RR 2.83, 95% CI 1.62-4.92). Topical budesonide was superior to placebo for induction of remission (RR 2.34, 95% CI 1.44-3.81). Combination therapy with topical 5-ASA and topical corticosteroids was superior to topical monotherapy with either agent. Topical tacrolimus was superior to placebo. Etrasimod was superior to placebo for induction (RR 4.71, 95% CI 1.2-18.49) and maintenance of remission (RR 2.08, 95% CI 1.31-3.32).
CONCLUSIONS
Topical 5-ASA and corticosteroids are effective for active UP. Topical 5-ASA may be effective for maintenance of remission. Tacrolimus may be effective for induction of remission. Etrasimod may be effective for induction and for maintenance of remission. Trials should include UP to expand the evidence base for this under-represented population.
Topics: Adult; Humans; Administration, Oral; Anti-Inflammatory Agents, Non-Steroidal; Budesonide; Colitis, Ulcerative; Mesalamine; Proctitis; Remission Induction; Tacrolimus
PubMed: 37589498
DOI: 10.1111/apt.17666 -
The Cochrane Database of Systematic... May 2022Medical abortion became an alternative method of pregnancy termination following the development of prostaglandins and antiprogesterone in the 1970s and 1980s. Recently,... (Review)
Review
BACKGROUND
Medical abortion became an alternative method of pregnancy termination following the development of prostaglandins and antiprogesterone in the 1970s and 1980s. Recently, synthesis inhibitors of oestrogen (such as letrozole) have also been used to enhance efficacy. The most widely researched drugs are prostaglandins (such as misoprostol, which has a strong uterotonic effect), mifepristone, mifepristone with prostaglandins, and letrozole with prostaglandins. More evidence is needed to identify the best dosage, regimen, and route of administration to optimise patient outcomes. This is an update of a review last published in 2011.
OBJECTIVES
To compare the effectiveness and side effects of different medical methods for first trimester abortion.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, Global Health, and LILACs on 28 February 2021. We also searched Clinicaltrials.gov and the World Health Organization's (WHO) International Clinical Trials Registry Platform, and reference lists of retrieved papers.
SELECTION CRITERIA
We considered randomised controlled trials (RCTs) that compared different medical methods for abortion before the 12th week of gestation. The primary outcome is failure to achieve complete abortion. Secondary outcomes are mortality, surgical evacuation, ongoing pregnancy at follow-up, time until passing of conceptus, blood transfusion, side effects and women's dissatisfaction with the method.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected and evaluated studies for inclusion, and assessed the risk of bias. We processed data using Review Manager 5 software. We assessed the certainty of the evidence using the GRADE approach.
MAIN RESULTS
We included 99 studies in the review (58 from the original review and 41 new studies). 1. Combined regimen mifepristone/prostaglandin Mifepristone dose: high-dose (600 mg) compared to low-dose (200 mg) mifepristone probably has similar effectiveness in achieving complete abortion (RR 1.07, 95% CI 0.87 to 1.33; I = 0%; 4 RCTs, 3494 women; moderate-certainty evidence). Prostaglandin dose: 800 µg misoprostol probably reduces abortion failure compared to 400 µg (RR 0.63, 95% CI 0.51 to 0.78; I= 0%; 3 RCTs, 4424 women; moderate-certainty evidence). Prostaglandin timing: misoprostol administered on day one probably achieves more success on complete abortion than on day three (RR 1.94, 95% CI 1.05 to 3.58; 1489 women; 1 RCT; moderate-certainty evidence). Administration strategy: there may be no difference in failure of complete abortion with self-administration at home compared with hospital administration (RR 1.63, 95% CI 0.68 to 3.94; I = 84%; 2263 women; 4 RCTs; low-certainty evidence), but failure may be higher when administered by nurses in hospital compared to by doctors in hospital (RR 2.69, 95% CI 1.39 to 5.22; I = 66%; 3 RCTs, 3056 women; low-certainty evidence). Administration route: oral misoprostol probably leads to more failures than the vaginal route (RR 2.38, 95% CI 1.46 to 3.87; I = 39%; 3 RCTs, 1704 women; moderate-certainty evidence) and may be associated with more frequent side effects such as nausea (RR 1.14, 95% CI 1.03 to 1.26; I = 0%; 2 RCTs, 1380 women; low-certainty evidence) and diarrhoea (RR 1.80 95% CI 1.49 to 2.17; I = 0%; 2 RCTs, 1379 women). Compared with the vaginal route, complete abortion failure is probably lower with sublingual (RR 0.68, 95% CI 0.22 to 2.11; I = 59%; 2 RCTs, 3229 women; moderate-certainty evidence) and may be lower with buccal administration (RR 0.71, 95% CI 0.34 to 1.46; I = 0%; 2 RCTs, 479 women; low-certainty evidence), but sublingual or buccal routes may lead to more side effects. Women may experience more vomiting with sublingual compared to buccal administration (RR 1.33, 95% CI 1.01 to 1.77; low-certainty evidence). 2. Mifepristone alone versus combined regimen The efficacy of mifepristone alone in achieving complete abortion compared to combined mifepristone/prostaglandin up to 12 weeks is unclear (RR of failure 3.25, 95% CI 0.81 to 13.09; I = 83%; 3 RCTs, 273 women; very low-certainty evidence). 3. Prostaglandin alone versus combined regimen Nineteen studies compared prostaglandin alone to a combined regimen (prostaglandin combined with mifepristone, letrozole, estradiol valerate, tamoxifen, or methotrexate). Compared to any of the combination regimens, misoprostol alone may increase the risk for failure to achieve complete abortion (RR of failure 2.39, 95% CI 1.89 to 3.02; I = 64%; 18 RCTs, 3471 women; low-certainty evidence), and with more diarrhoea. 4. Prostaglandin alone (route of administration) Oral misoprostol alone may lead to more failures in complete abortion than the vaginal route (RR 3.68, 95% CI 1.56 to 8.71, 2 RCTs, 216 women; low-certainty evidence). Failure to achieve complete abortion may be slightly reduced with sublingual compared with vaginal (RR 0.69, 95% CI 0.37 to 1.28; I = 87%; 5 RCTs, 2705 women; low-certainty evidence) and oral administration (RR 0.58, 95% CI 0.11 to 2.99; I = 66%; 2 RCTs, 173 women). Failure to achieve complete abortion may be similar or slightly higher with sublingual administration compared to buccal administration (RR 1.11, 95% CI 0.71 to 1.74; 1 study, 401 women).
AUTHORS' CONCLUSIONS
Safe and effective medical abortion methods are available. Combined regimens (prostaglandin combined with mifepristone, letrozole, estradiol valerate, tamoxifen, or methotrexate) may be more effective than single agents (prostaglandin alone or mifepristone alone). In the combined regimen, the dose of mifepristone can probably be lowered to 200 mg without significantly decreasing effectiveness. Vaginal misoprostol is probably more effective than oral administration, and may have fewer side effects than sublingual or buccal. Some results are limited by the small numbers of participants on which they are based. Almost all studies were conducted in settings with good access to emergency services, which may limit the generalisability of these results.
Topics: Abortifacient Agents, Nonsteroidal; Abortion, Spontaneous; Diarrhea; Drug Therapy, Combination; Estradiol; Female; Humans; Letrozole; Methotrexate; Mifepristone; Misoprostol; Oxytocics; Pregnancy; Pregnancy Trimester, First; Prostaglandins; Tamoxifen
PubMed: 35608608
DOI: 10.1002/14651858.CD002855.pub5 -
British Journal of Anaesthesia Jan 2023Sedation techniques and drugs are increasingly used in children undergoing imaging procedures. In this systematic review and meta-analysis, we present an overview of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Sedation techniques and drugs are increasingly used in children undergoing imaging procedures. In this systematic review and meta-analysis, we present an overview of literature concerning sedation of children aged 0-8 yr for magnetic resonance imaging (MRI) procedures using needle-free pharmacological techniques.
METHODS
Embase, MEDLINE, Web of Science, and Cochrane databases were systematically searched for studies on the use of needle-free pharmacological sedation techniques for MRI procedures in children aged 0-8 yr. Studies using i.v. or i.m. medication or advanced airway devices were excluded. We performed a meta-analysis on sedation success rate. Secondary outcomes were onset time, duration, recovery, and adverse events.
RESULTS
Sixty-seven studies were included, with 22 380 participants. The pooled success rate for oral chloral hydrate was 94% (95% confidence interval [CI]: 0.91-0.96); for oral chloral hydrate and intranasal dexmedetomidine 95% (95% CI: 0.92-0.97); for rectal, oral, or intranasal midazolam 36% (95% CI: 0.14-0.65); for oral pentobarbital 99% (95% CI: 0.90-1.00); for rectal thiopental 92% (95% CI: 0.85-0.96); for oral melatonin 75% (95% CI: 0.54-0.89); for intranasal dexmedetomidine 62% (95% CI: 0.38-0.82); for intranasal dexmedetomidine and midazolam 94% (95% CI: 0.78-0.99); and for inhaled sevoflurane 98% (95% CI: 0.97-0.99).
CONCLUSIONS
We found a large variation in medication, dosage, and route of administration for needle-free sedation. Success rates for sedation techniques varied between 36% and 98%.
Topics: Child; Humans; Hypnotics and Sedatives; Midazolam; Dexmedetomidine; Administration, Oral; Chloral Hydrate; Administration, Intranasal; Conscious Sedation
PubMed: 36283870
DOI: 10.1016/j.bja.2022.09.007 -
Breast (Edinburgh, Scotland) Jun 2023Patients with HER2+ breast cancer (BC) frequently develop leptomeningeal metastases (LM). While HER2-targeted therapies have demonstrated efficacy in the neoadjuvant,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Patients with HER2+ breast cancer (BC) frequently develop leptomeningeal metastases (LM). While HER2-targeted therapies have demonstrated efficacy in the neoadjuvant, adjuvant, and metastatic settings, including for parenchymal brain metastases, their efficacy for patients with LM has not been studied in a randomized controlled trial. However, several single-armed prospective studies, case series and case reports have studied oral, intravenous, or intrathecally administered HER2-targeted therapy regimens for patients with HER2+ BC LM.
METHODS
We conducted a systematic review and meta-analysis of individual patient data to evaluate the efficacy of HER2-targeted therapies in HER2+ BC LM in accordance with PRISMA guidelines. Targeted therapies evaluated were trastuzumab (intrathecal or intravenous), pertuzumab, lapatinib, neratinib, tucatinib, trastuzumab-emtansine and trastuzumab-deruxtecan. The primary endpoint was overall survival (OS), with CNS-specific progression-free survival (PFS) as a secondary endpoint.
RESULTS
7780 abstracts were screened, identifying 45 publications with 208 patients, corresponding to 275 lines of HER2-targeted therapy for BC LM which met inclusion criteria. In univariable and multivariable analyses, we observed no significant difference in OS and CNS-specific PFS between intrathecal trastuzumab compared to oral or intravenous administration of HER2-targeted therapy. Anti-HER2 monoclonal antibody-based regimens did not demonstrate superiority over HER2 tyrosine kinase inhibitors. In a cohort of 15 patients, treatment with trastuzumab-deruxtecan was associated with prolonged OS compared to other HER2-targeted therapies and compared to trastuzumab-emtansine.
CONCLUSIONS
The results of this meta-analysis, comprising the limited data available, suggest that intrathecal administration of HER2-targeted therapy for patients with HER2+ BC LM confers no additional benefit over oral and/or IV treatment regimens. Although the number of patients receiving trastuzumab deruxtecan in this cohort is small, this novel agent offers promise for this patient population and requires further investigation in prospective studies.
Topics: Female; Humans; Ado-Trastuzumab Emtansine; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Prospective Studies; Randomized Controlled Trials as Topic; Receptor, ErbB-2; Trastuzumab; Meningeal Neoplasms
PubMed: 37156650
DOI: 10.1016/j.breast.2023.04.008 -
ESC Heart Failure Oct 2022This review aimed to assess whether oral iron supplementation in a chronic heart failure (HF) population with iron deficiency (ID) or mild anaemia is safe and effective... (Meta-Analysis)
Meta-Analysis Review
AIMS
This review aimed to assess whether oral iron supplementation in a chronic heart failure (HF) population with iron deficiency (ID) or mild anaemia is safe and effective according to evidence-based medicine.
METHODS
We retrieved 1803 records from the PubMed, Embase, and the Cochrane Library databases from 1 January 1991 to 15 September 2021. The clinical outcome of oral iron supplementation for ID anaemia in patients with HF was the primary endpoint. The primary safety measures included adverse events and all-cause mortality, and efficacy measures included transferrin saturation (Tsat), ferritin levels, and the 6-min walk test (6MWT). The rate ratio (RR) was used to pool the efficacy measures.
RESULTS
Five randomized controlled trials that compared oral iron treatment for patients with the placebo group and included a combined total of 590 participants were analysed. No significant difference was found in all-cause death between oral iron treatment and placebo groups (RR = 0.77; 95% confidence intervals (CI), 0.46-1.29, Z = 0.98; P = 0.33). However, adverse events were not significantly higher in the iron treatment group (RR = 0.83; 95% CI, 0.60-1.16, Z = 1.07; P = 0.28). In addition, ferritin levels and Tsat were slightly increased after iron complex administration in patients with HF but were not statistically significant (ferritin: mean difference [MD] = 2.70, 95% CI, -2.41 to 7.81, Z = 1.04; P = 0.30; Tsat: MD = 27.42, 95% CI, -4.93 to 59.78, Z = 1.66; P = 0.10). No significant difference was found in exercise capacity, as indicated by the 6MWT results (MD = 59.60, 95% CI, -17.89 to 137.08, Z = 1.51; P = 0.13). We also analysed two non-randomized controlled trials with follow-up results showing that oral iron supplementation increased serum iron levels (MD = 28.87, 95% CI, 1.62-56.12, Z = 2.08; P = 0.04).
CONCLUSIONS
Based on the current findings, oral iron supplementation can increase serum iron levels in patients with HF and ID or mild anaemia but does not improve Tsat and 6MWT. In addition, oral iron supplementation is relatively safe.
Topics: Humans; Iron; Iron Deficiencies; Ferritins; Heart Failure; Anemia; Dietary Supplements; Randomized Controlled Trials as Topic
PubMed: 35758130
DOI: 10.1002/ehf2.14020 -
Revista Portuguesa de Cardiologia :... Feb 2022Oleuropein is a polyphenol found in olive trees that has shown beneficial effects in animal studies and potentially in human health, although few studies have been... (Review)
Review
Oleuropein is a polyphenol found in olive trees that has shown beneficial effects in animal studies and potentially in human health, although few studies have been performed to confirm this hypothesis in the latter population. Previous studies related its antioxidant activity to cardioprotective effects and showed a positive correlation between dose and response. We thus aimed to assess the cardioprotective effect of oleuropein and olive leaf extract in animal experiments. A literature search was conducted in June 2020 in the PubMed, Scopus and Web of Science databases. The descriptors "oleuropein" and "oleuropein aglycone" identified 12 articles for qualitative synthesis. Risk of bias was assessed by SYRCLE's RoB tool for animal studies. The results demonstrate evidence of a positive association between the administration of oleuropein and olive leaf extract and improvement in outcomes in hypertension, heart failure, myocardial infarction. renal hypertension and diabetes. This review presents a positive effect of oleuropein and olive leaf extract administration on cardiovascular parameters in animal studies.
PubMed: 36062705
DOI: 10.1016/j.repc.2021.05.011 -
Research and Practice in Thrombosis and... Mar 2023Direct oral anticoagulants (DOACs) are widely used in patients with atrial fibrillation and venous thromboembolism. However, DOACs have important potential drug-drug... (Review)
Review
BACKGROUND
Direct oral anticoagulants (DOACs) are widely used in patients with atrial fibrillation and venous thromboembolism. However, DOACs have important potential drug-drug interactions (DDIs) with several classes of drugs. In particular, antiepileptic (AE) drugs may induce cytochrome P450 3A4 or P-glycoprotein. Co-administration of DOACs and AE drugs may result in lower DOAC drug levels and reduced DOAC efficacy. However, the clinical significance of such DDIs is uncertain.
OBJECTIVES
The aim of this systematic review was to generate an updated review of these DDIs and their clinical relevance, given the rapidly evolving knowledge relating to DOAC and AE DDIs.
METHODS
We searched the MEDLINE and Embase databases for studies reporting clinical adverse outcomes (thrombotic events, bleeding events, and all-cause mortality) in patients concomitantly taking DOACs and AE drugs.
RESULTS
We retrieved 874 studies of which 15 were deemed eligible for this review, including 4 congress abstracts, 3 case reports, 2 letters to the editor, 5 retrospective cohorts, and 1 prospective cohort study. No randomized clinical trials were found. Most of the included studies reported thrombotic events, 3 studies reported major bleeding, and one study reported all-cause mortality associated with DOAC and AE drug administration. Substantial differences in the study designs did not allow for a meta-analysis to be performed.
CONCLUSION
The current literature assessing these adverse clinical outcomes from DOAC and AE drug co-administration is limited. Although the available data point to a possible increased risk of thrombotic events, they are insufficient to draw definitive conclusions. Well-designed clinical studies are of utmost importance.
PubMed: 37122531
DOI: 10.1016/j.rpth.2023.100137