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Molecular Psychiatry Aug 2023The serotonin hypothesis of depression is still influential. We aimed to synthesise and evaluate evidence on whether depression is associated with lowered serotonin... (Meta-Analysis)
Meta-Analysis
The serotonin hypothesis of depression is still influential. We aimed to synthesise and evaluate evidence on whether depression is associated with lowered serotonin concentration or activity in a systematic umbrella review of the principal relevant areas of research. PubMed, EMBASE and PsycINFO were searched using terms appropriate to each area of research, from their inception until December 2020. Systematic reviews, meta-analyses and large data-set analyses in the following areas were identified: serotonin and serotonin metabolite, 5-HIAA, concentrations in body fluids; serotonin 5-HT receptor binding; serotonin transporter (SERT) levels measured by imaging or at post-mortem; tryptophan depletion studies; SERT gene associations and SERT gene-environment interactions. Studies of depression associated with physical conditions and specific subtypes of depression (e.g. bipolar depression) were excluded. Two independent reviewers extracted the data and assessed the quality of included studies using the AMSTAR-2, an adapted AMSTAR-2, or the STREGA for a large genetic study. The certainty of study results was assessed using a modified version of the GRADE. We did not synthesise results of individual meta-analyses because they included overlapping studies. The review was registered with PROSPERO (CRD42020207203). 17 studies were included: 12 systematic reviews and meta-analyses, 1 collaborative meta-analysis, 1 meta-analysis of large cohort studies, 1 systematic review and narrative synthesis, 1 genetic association study and 1 umbrella review. Quality of reviews was variable with some genetic studies of high quality. Two meta-analyses of overlapping studies examining the serotonin metabolite, 5-HIAA, showed no association with depression (largest n = 1002). One meta-analysis of cohort studies of plasma serotonin showed no relationship with depression, and evidence that lowered serotonin concentration was associated with antidepressant use (n = 1869). Two meta-analyses of overlapping studies examining the 5-HT receptor (largest n = 561), and three meta-analyses of overlapping studies examining SERT binding (largest n = 1845) showed weak and inconsistent evidence of reduced binding in some areas, which would be consistent with increased synaptic availability of serotonin in people with depression, if this was the original, causal abnormaly. However, effects of prior antidepressant use were not reliably excluded. One meta-analysis of tryptophan depletion studies found no effect in most healthy volunteers (n = 566), but weak evidence of an effect in those with a family history of depression (n = 75). Another systematic review (n = 342) and a sample of ten subsequent studies (n = 407) found no effect in volunteers. No systematic review of tryptophan depletion studies has been performed since 2007. The two largest and highest quality studies of the SERT gene, one genetic association study (n = 115,257) and one collaborative meta-analysis (n = 43,165), revealed no evidence of an association with depression, or of an interaction between genotype, stress and depression. The main areas of serotonin research provide no consistent evidence of there being an association between serotonin and depression, and no support for the hypothesis that depression is caused by lowered serotonin activity or concentrations. Some evidence was consistent with the possibility that long-term antidepressant use reduces serotonin concentration.
Topics: Humans; Depression; Serotonin; Receptor, Serotonin, 5-HT1A; Tryptophan; Hydroxyindoleacetic Acid; Antidepressive Agents; Serotonin Plasma Membrane Transport Proteins
PubMed: 35854107
DOI: 10.1038/s41380-022-01661-0 -
European Urology Jul 2023Whether prostate-specific membrane antigen positron emission tomography (PSMA-PET) should replace conventional imaging modalities (CIM) for initial staging of... (Meta-Analysis)
Meta-Analysis Review
Head-to-head Comparison of the Diagnostic Accuracy of Prostate-specific Membrane Antigen Positron Emission Tomography and Conventional Imaging Modalities for Initial Staging of Intermediate- to High-risk Prostate Cancer: A Systematic Review and Meta-analysis.
CONTEXT
Whether prostate-specific membrane antigen positron emission tomography (PSMA-PET) should replace conventional imaging modalities (CIM) for initial staging of intermediate-high risk prostate cancer (PCa) requires definitive evidence on their relative diagnostic abilities.
OBJECTIVE
To perform head-to-head comparisons of PSMA-PET and CIM including multiparametric magnetic resonance imaging (mpMRI), computed tomography (CT) and bone scan (BS) for upfront staging of tumour, nodal, and bone metastasis.
EVIDENCE ACQUISITION
A search of the PubMed, EMBASE, CENTRAL, and Scopus databases was conducted from inception to December 2021. Only studies in which patients underwent both PSMA-PET and CIM and imaging was referenced against histopathology or composite reference standards were included. Quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) checklist and its extension for comparative reviews (QUADAS-C). Pairwise comparisons of the sensitivity and specificity of PSMA-PET versus CIM were performed by adding imaging modality as a covariate to bivariate mixed-effects meta-regression models. The likelihood ratio test was applied to determine whether statistically significant differences existed.
EVIDENCE SYNTHESIS
A total of 31 studies (2431 patients) were included. PSMA-PET/MRI was more sensitive than mpMRI for detection of extra-prostatic extension (78.7% versus 52.9%) and seminal vesicle invasion (66.7% versus 51.0%). For nodal staging, PSMA-PET was more sensitive and specific than mpMRI (73.7% versus 38.9%, 97.5% versus 82.6%) and CT (73.2% versus 38.5%, 97.8% versus 83.6%). For bone metastasis staging, PSMA-PET was more sensitive and specific than BS with or without single-photon emission computerised tomography (98.0% versus 73.0%, 96.2% versus 79.1%). A time interval between imaging modalities >1 month was identified as a source of heterogeneity across all nodal staging analyses.
CONCLUSIONS
Direct comparisons revealed that PSMA-PET significantly outperforms CIM, which suggests that PSMA-PET should be used as a first-line approach for the initial staging of PCa.
PATIENT SUMMARY
We reviewed direct comparisons of the ability of a scan method called PSMA-PET (prostate-specific membrane antigen positron emission tomography) and current imaging methods to detect the spread of prostate cancer outside the prostate gland. We found that PSMA-PET is more accurate for detection of the spread of prostate cancer to adjacent tissue, nearby lymph nodes, and bones.
Topics: Male; Humans; Prostate; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Prostatic Neoplasms; Magnetic Resonance Imaging; Gallium Radioisotopes; Neoplasm Staging
PubMed: 37032189
DOI: 10.1016/j.eururo.2023.03.001 -
Periodontology 2000 Feb 2024Platelet-rich fibrin (PRF) has been characterized as a regenerative biomaterial that is fully resorbed within a typical 2-3 week period. Very recently, however, a...
Platelet-rich fibrin (PRF) has been characterized as a regenerative biomaterial that is fully resorbed within a typical 2-3 week period. Very recently, however, a novel heating process was shown to extend the working properties of PRP/PRF from a standard 2-3 week period toward a duration of 4-6 months. Numerous clinicians have now utilized this extended-PRF (e-PRF) membrane as a substitute for collagen barrier membranes in various clinical applications, such as guided tissue/bone regeneration. This review article summarizes the scientific work to date on this novel technology, including its current and future applications in periodontology, implant dentistry, orthopedics and facial aesthetics. A systematic review was conducted investigating key terms including "Bio-Heat," "albumin gel," "albumin-PRF," "Alb-PRF," "extended-PRF," "e-PRF," "activated plasma albumin gel," and "APAG" by searching databases such as MEDLINE, EMBASE and PubMed. Findings from preclinical studies demonstrate that following a simple 10-min heating process, the transformation of the liquid plasma albumin layer into a gel-like injectable albumin gel extends the resorption properties to at least 4 months according to ISO standard 10 993 (subcutaneous animal model). Several clinical studies have now demonstrated the use of e-PRF membranes as a replacement for collagen membranes in GTR/GBR procedures, closing lateral windows in sinus grafting procedures, for extraction site management, and as a stable biological membrane during recession coverage procedures. Furthermore, Alb-PRF may also be injected as a regenerative biological filler that lasts extended periods with advantages in joint injections, osteoarthritis and in the field of facial aesthetics. This article highlights the marked improvement in the stability and degradation properties of the novel Alb-PRF/e-PRF technology with its widespread future potential use as a potential replacement for collagen membranes with indications including extraction site management, GBR procedures, lateral sinus window closure, recession coverage among others, and further highlights its use as a biological regenerative filler for joint injections and facial aesthetics. It is hoped that this review will pioneer future opportunities and research development in the field, leading to further progression toward more natural and less costly biomaterials for use in medicine and dentistry.
Topics: Animals; Humans; Biocompatible Materials; Bone Regeneration; Guided Tissue Regeneration, Periodontal; Membranes, Artificial; Platelet-Rich Fibrin
PubMed: 37986559
DOI: 10.1111/prd.12537 -
Phytomedicine : International Journal... Jul 2023Every day the skin is constantly exposed to several harmful factors that induce oxidative stress. When the cells are incapable to maintain the balance between... (Review)
Review
BACKGROUND
Every day the skin is constantly exposed to several harmful factors that induce oxidative stress. When the cells are incapable to maintain the balance between antioxidant defenses and reactive oxygen species, the skin no longer can keep its integrity and homeostasis. Chronic inflammation, premature skin aging, tissue damage, and immunosuppression are possible consequences induced by sustained exposure to environmental and endogenous reactive oxygen species. Skin immune and non-immune cells together with the microbiome are essential to efficiently trigger skin immune responses to stress. For this reason, an ever-increasing demand for novel molecules capable of modulating immune functions in the skin has risen the level of their development, particularly in the field of natural product-derived molecules.
PURPOSE
In this review, we explore different classes of molecules that showed evidence in modulate skin immune responses, as well as their target receptors and signaling pathways. Moreover, we describe the role of polyphenols, polysaccharides, fatty acids, peptides, and probiotics as possible treatments for skin conditions, including wound healing, infection, inflammation, allergies, and premature skin aging.
METHODS
Literature was searched, analyzed, and collected using databases, including PubMed, Science Direct, and Google Scholar. The search terms used included "Skin", "wound healing", "natural products", "skin microbiome", "immunomodulation", "anti-inflammatory", "antioxidant", "infection", "UV radiation", "polyphenols", "polysaccharides", "fatty acids", "plant oils", "peptides", "antimicrobial peptides", "probiotics", "atopic dermatitis", "psoriasis", "auto-immunity", "dry skin", "aging", etc., and several combinations of these keywords.
RESULTS
Natural products offer different solutions as possible treatments for several skin conditions. Significant antioxidant and anti-inflammatory activities were reported, followed by the ability to modulate immune functions in the skin. Several membrane-bound immune receptors in the skin recognize diverse types of natural-derived molecules, promoting different immune responses that can improve skin conditions.
CONCLUSION
Despite the increasing progress in drug discovery, several limiting factors need future clarification. Understanding the safety, biological activities, and precise mechanisms of action is a priority as well as the characterization of the active compounds responsible for that. This review provides directions for future studies in the development of new molecules with important pharmaceutical and cosmeceutical value.
Topics: Humans; Skin Aging; Reactive Oxygen Species; Biological Products; Antioxidants; Inflammation; Anti-Inflammatory Agents; Polyphenols; Peptides; Polysaccharides
PubMed: 37119762
DOI: 10.1016/j.phymed.2023.154824 -
The Lancet. Respiratory Medicine Oct 2023Although outcomes of patients after cardiac arrest remain poor, studies have suggested that extracorporeal cardiopulmonary resuscitation (ECPR) might improve survival... (Meta-Analysis)
Meta-Analysis
Extracorporeal cardiopulmonary resuscitation versus conventional cardiopulmonary resuscitation in adults with cardiac arrest: a comparative meta-analysis and trial sequential analysis.
BACKGROUND
Although outcomes of patients after cardiac arrest remain poor, studies have suggested that extracorporeal cardiopulmonary resuscitation (ECPR) might improve survival and neurological outcomes. We aimed to investigate any potential benefits of using ECPR over conventional cardiopulmonary resuscitation (CCPR) in patients with out-of-hospital cardiac arrest (OHCA) and in-hospital cardiac arrest (IHCA).
METHODS
In this systematic review and meta-analysis, we searched MEDLINE via PubMed, Embase, and Scopus from Jan 1, 2000, to April 1, 2023, for randomised controlled trials and propensity-score matched studies. We included studies comparing ECPR with CCPR in adults (aged ≥18 years) with OHCA and IHCA. We extracted data from published reports using a prespecified data extraction form. We did random-effects (Mantel-Haenszel) meta-analyses and rated the certainty of evidence using the Grading of Recommendations, Assessments, Developments, and Evaluations (GRADE) approach. We rated the risk of bias of randomised controlled trials using the Cochrane risk-of-bias 2.0 tool, and that of observational studies using the Newcastle-Ottawa Scale. The primary outcome was in-hospital mortality. Secondary outcomes included complications during extracorporeal membrane oxygenation, short-term (from hospital discharge to 30 days after cardiac arrest) and long-term (≥90 days after cardiac arrest) survival with favourable neurological outcomes (defined as cerebral performance category scores 1 or 2), and survival at 30 days, 3 months, 6 months, and 1 year after cardiac arrest. We also did trial sequential analyses to evaluate the required information sizes in the meta-analyses to detect clinically relevant reductions in mortality.
FINDINGS
We included 11 studies (4595 patients receiving ECPR and 4597 patients receiving CCPR) in the meta-analysis. ECPR was associated with a significant reduction in overall in-hospital mortality (OR 0·67, 95% CI 0·51-0·87; p=0·0034; high certainty), without evidence of publication bias (p=0·19); the trial sequential analysis was concordant with the meta-analysis. When considering IHCA only, in-hospital mortality was lower in patients receiving ECPR than in those receiving CCPR (0·42, 0·25-0·70; p=0·0009), whereas when considering OHCA only, no differences were found (0·76, 0·54-1·07; p=0·12). Centre volume (ie, the number of ECPR runs done per year in each centre) was associated with reductions in odds of mortality (regression coefficient per doubling of centre volume -0·17, 95% CI -0·32 to -0·017; p=0·030). ECPR was also associated with an increased rate of short-term (OR 1·65, 95% CI 1·02-2·68; p=0·042; moderate certainty) and long-term (2·04, 1·41-2·94; p=0·0001; high certainty) survival with favourable neurological outcomes. Additionally, patients receiving ECPR had increased survival at 30-day (OR 1·45, 95% CI 1·08-1·96; p=0·015), 3-month (3·98, 1·12-14·16; p=0·033), 6-month (1·87, 1·36-2·57; p=0·0001), and 1-year (1·72, 1·52-1·95; p<0·0001) follow-ups.
INTERPRETATION
Compared with CCPR, ECPR reduced in-hospital mortality and improved long-term neurological outcomes and post-arrest survival, particularly in patients with IHCA. These findings suggest that ECPR could be considered for eligible patients with IHCA, although further research into patients with OHCA is warranted.
FUNDING
None.
Topics: Humans; Adult; Adolescent; Treatment Outcome; Cardiopulmonary Resuscitation; Out-of-Hospital Cardiac Arrest; Extracorporeal Membrane Oxygenation; Time Factors; Retrospective Studies
PubMed: 37230097
DOI: 10.1016/S2213-2600(23)00137-6 -
American Journal of Obstetrics &... Aug 2023Vaginal progesterone and cervical cerclage are both effective interventions for reducing preterm birth. It is currently unclear whether combined therapy offers superior... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Vaginal progesterone and cervical cerclage are both effective interventions for reducing preterm birth. It is currently unclear whether combined therapy offers superior effectiveness than single therapy. This study aimed to determine the efficacy of combining cervical cerclage and vaginal progesterone in the prevention of preterm birth.
DATA SOURCES
We searched Medline (Ovid), EMBASE (Ovid), PsycINFO (Ovid), CINAHL (EBSCOhost), Cochrane Library (Wiley), and Scopus (from their inception to 2020).
STUDY ELIGIBILITY CRITERIA
The review accepted randomized and pseudorandomized control trials, nonrandomized experimental control trials, and cohort studies. High risk patients (shortened cervical length <25mm or previous preterm birth) who were assigned cervical cerclage, vaginal progesterone, or both for the prevention of preterm birth were included. Only singleton pregnancies were assessed.
METHODS
The primary outcome was birth <37 weeks. Secondary outcomes included birth <28 weeks, <32 weeks and <34 weeks, gestational age at delivery, days between intervention and delivery, preterm premature rupture of membranes, cesarean delivery, neonatal mortality, neonatal intensive care unit admission, intubation, and birthweight. Following title and full-text screening, 11 studies were included in the final analysis. Risk of bias was assessed using the Cochrane Collaboration tool for assessing the risk of bias (ROBINS-I and RoB-2). Quality of evidence was assessed using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) tool.
RESULTS
Combined therapy was associated with lower risk of preterm birth at <37 weeks than cerclage alone (risk ratio, 0.51; 95% confidence interval, 0.37-0.79) or progesterone alone (risk ratio, 0.75; 95% confidence interval, 0.58-0.96). Compared with cerclage only, combined therapy was associated with preterm birth at <34 weeks, <32 weeks, or <28 weeks, decreased neonatal mortality, increased birthweight, increased gestational age, and a longer interval between intervention and delivery. Compared with progesterone alone, combined therapy was associated with preterm birth at <32 weeks, <28 weeks, decreased neonatal mortality, increased birthweight, and increased gestational age. There were no differences in any other secondary outcomes.
CONCLUSION
Combined treatment of cervical cerclage and vaginal progesterone could potentially result in a greater reduction in preterm birth than in single therapy. Further, well-conducted and adequately powered randomized controlled trials are needed to assess these promising findings.
Topics: Pregnancy; Female; Infant, Newborn; Humans; Progesterone; Premature Birth; Cerclage, Cervical; Birth Weight; Administration, Intravaginal
PubMed: 37211087
DOI: 10.1016/j.ajogmf.2023.101024 -
American Journal of Obstetrics &... Jul 2023An emergency (rescue) cervical cerclage can be offered to pregnant women presenting with dilatation and prolapsed membranes in the second trimester of pregnancy because... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
An emergency (rescue) cervical cerclage can be offered to pregnant women presenting with dilatation and prolapsed membranes in the second trimester of pregnancy because of cervical insufficiency. This study aimed to investigate the effectiveness of an emergency cerclage in both singleton and twin pregnancies in the prevention of extreme premature birth.
DATA SOURCES
We performed a systematic literature search in PubMed and Embase from inception to June 2022 for transvaginal cervical emergency cerclages.
STUDY ELIGIBILITY CRITERIA
All studies on transvaginal cervical emergency cerclages with at least 5 patients and reporting survival were included.
METHODS
Included studies were assessed for quality and risk of bias with an adjusted Quality In Prognosis Studies tool. Random-effects meta-analyses and meta-regressions were performed for the primary outcome: survival.
RESULTS
Our search yielded 96 studies, incorporating 3239 women, including 14 studies with an expectant management control group, incorporating 746 women. Overall survival after cervical emergency cerclage was 74%, with a fetal survival of 88% and neonatal survival of 90%. Singleton and twin pregnancies showed similar survival, with a pregnancy prolongation of 52 and 37 days and a gestational age at delivery of 30 and 28 weeks, respectively. Meta-regression analyses indicated a significant inverse association between mean gestational age at diagnosis and pregnancy prolongation and no association between dilatation or gestational age at diagnosis and gestational age at delivery. Compared with expectant management, emergency cerclage significantly increased overall survival by 43%, fetal survival by 17% and neonatal survival by 22%, along with a significant pregnancy prolongation of 37 days and reduction in delivery at <28 weeks of gestation of 55%. These effects were more profound in singleton pregnancies than in twin pregnancies.
CONCLUSION
This systematic review indicates that, in pregnancies threatened by extreme premature birth because of cervical insufficiency, emergency cerclage leads to significantly higher survival, accompanied by significant pregnancy prolongation and reduction in delivery at <28 weeks of gestation, compared with expectant management. The mean gestational age at delivery was 30 weeks, independent of dilatation or gestational age at diagnosis. Survival was similar for singleton and twin pregnancies, implying that emergency cerclage should be considered in both.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Infant; Pregnancy, Twin; Cerclage, Cervical; Premature Birth; Cervix Uteri; Pregnancy Complications
PubMed: 37084870
DOI: 10.1016/j.ajogmf.2023.100971 -
The Cochrane Database of Systematic... Nov 2023Acute otitis media (AOM) is one of the most common diseases in childhood for which antibiotics are commonly prescribed; a systematic review reported a pooled prevalence... (Review)
Review
BACKGROUND
Acute otitis media (AOM) is one of the most common diseases in childhood for which antibiotics are commonly prescribed; a systematic review reported a pooled prevalence of 85.6% in high-income countries. This is an update of a Cochrane Review first published in the Cochrane Library in 1997 and updated in 1999, 2005, 2009, 2013 and 2015.
OBJECTIVES
To assess the effects of antibiotics for children with AOM.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, Current Contents, CINAHL, LILACS and two trial registers. The date of the search was 14 February 2023.
SELECTION CRITERIA
We included randomised controlled trials comparing 1) antimicrobial drugs with placebo, and 2) immediate antibiotic treatment with expectant observation (including delayed antibiotic prescribing) in children with AOM.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened trials for inclusion and extracted data using the standard methodological procedures recommended by Cochrane. Our primary outcomes were: 1) pain at various time points (24 hours, two to three days, four to seven days, 10 to 14 days), and 2) adverse effects likely to be related to the use of antibiotics. Secondary outcomes were: 1) abnormal tympanometry findings, 2) tympanic membrane perforation, 3) contralateral otitis (in unilateral cases), 4) AOM recurrences, 5) serious complications related to AOM and 6) long-term effects (including the number of parent-reported AOM symptom episodes, antibiotic prescriptions and health care utilisation as assessed at least one year after randomisation). We used the GRADE approach to rate the overall certainty of evidence for each outcome of interest.
MAIN RESULTS
Antibiotics versus placebo We included 13 trials (3401 children and 3938 AOM episodes) from high-income countries, which we assessed at generally low risk of bias. Antibiotics do not reduce pain at 24 hours (risk ratio (RR) 0.89, 95% confidence interval (CI) 0.78 to 1.01; 5 trials, 1394 children; high-certainty evidence), or at four to seven days (RR 0.76, 95% CI 0.50 to 1.14; 7 trials, 1264 children), but result in almost a third fewer children having pain at two to three days (RR 0.71, 95% CI 0.58 to 0.88; number needed to treat for an additional beneficial outcome (NNTB) 20; 7 trials, 2320 children; high-certainty evidence), and likely result in two-thirds fewer having pain at 10 to 12 days (RR 0.33, 95% CI 0.17 to 0.66; NNTB 7; 1 trial, 278 children; moderate-certainty evidence). Antibiotics increase the risk of adverse events such as vomiting, diarrhoea or rash (RR 1.38, 95% CI 1.16 to 1.63; number needed to treat for an additional harmful outcome (NNTH) 14; 8 trials, 2107 children; high-certainty evidence). Antibiotics reduce the risk of children having abnormal tympanometry findings at two to four weeks (RR 0.83, 95% CI 0.72 to 0.96; NNTB 11; 7 trials, 2138 children), slightly reduce the risk of experiencing tympanic membrane perforations (RR 0.43, 95% CI 0.21 to 0.89; NNTB 33; 5 trials, 1075 children) and halve the risk of contralateral otitis episodes (RR 0.49, 95% CI 0.25 to 0.95; NNTB 11; 4 trials, 906 children). However, antibiotics do not reduce the risk of abnormal tympanometry findings at six to eight weeks (RR 0.89, 95% CI 0.70 to 1.13; 3 trials, 953 children) and at three months (RR 0.94, 95% CI 0.66 to 1.34; 3 trials, 809 children) or late AOM recurrences (RR 0.94, 95% CI 0.79 to 1.11; 6 trials, 2200 children). Severe complications were rare, and the evidence suggests that serious complications do not differ between children treated with either antibiotics or placebo. Immediate antibiotics versus expectant observation We included six trials (1556 children) from high-income countries. The evidence suggests that immediate antibiotics may result in a reduction of pain at two to three days (RR 0.53, 95% CI 0.35 to 0.79; NNTB 8; 1 trial, 396 children; low-certainty evidence), but probably do not reduce the risk of pain at three to seven days (RR 0.75, 95% CI 0.50 to 1.12; 4 trials, 959 children; moderate-certainty evidence), and may not reduce the risk of pain at 11 to 14 days (RR 0.91, 95% CI 0.75 to 1.10; 1 trial, 247 children; low-certainty evidence). Immediate antibiotics increase the risk of vomiting, diarrhoea or rash (RR 1.87, 95% CI 1.39 to 2.51; NNTH 10; 3 trials, 946 children; high-certainty evidence). Immediate antibiotics probably do not reduce the proportion of children with abnormal tympanometry findings at four weeks and evidence suggests that immediate antibiotics may not reduce the risk of tympanic membrane perforation and AOM recurrences. No serious complications occurred in either group.
AUTHORS' CONCLUSIONS
This review reveals that antibiotics probably have no effect on pain at 24 hours, a slight effect on pain in the days following and only a modest effect on the number of children with tympanic perforations, contralateral otitis episodes and abnormal tympanometry findings at two to four weeks compared with placebo in children with AOM. In high-income countries, most cases of AOM spontaneously remit without complications. The benefits of antibiotics must be weighed against the possible harms: for every 14 children treated with antibiotics, one child experienced an adverse event (such as vomiting, diarrhoea or rash) that would not have occurred if antibiotics were withheld. For most children with mild disease in high-income countries, an expectant observational approach seems justified. Therefore, clinical management should emphasise advice about adequate analgesia and the limited role for antibiotics.
Topics: Child; Humans; Anti-Bacterial Agents; Tympanic Membrane Perforation; Acute Disease; Otitis Media; Pain; Diarrhea; Exanthema; Vomiting
PubMed: 37965923
DOI: 10.1002/14651858.CD000219.pub5 -
American Journal of Obstetrics &... Jul 2023Various prophylactic antibiotic regimens are used in the management of preterm premature rupture of membranes. We investigated the efficacy and safety of these regimens... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Various prophylactic antibiotic regimens are used in the management of preterm premature rupture of membranes. We investigated the efficacy and safety of these regimens in terms of maternal and neonatal outcomes.
DATA SOURCES
We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials from inception to July 20, 2021.
STUDY ELIGIBILITY CRITERIA
We included randomized controlled trials involving pregnant women with preterm premature rupture of membranes before 37 weeks of gestation and a comparison of ≥2 of the following 10 antibiotic regimens: control/placebo, erythromycin, clindamycin, clindamycin plus gentamicin, penicillins, cephalosporins, co-amoxiclav, co-amoxiclav plus erythromycin, aminopenicillins plus macrolides, and cephalosporins plus macrolides.
METHODS
Two investigators independently extracted published data and assessed the risk of bias with a standard procedure following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Network meta-analysis was conducted using the random-effects model.
RESULTS
A total of 23 studies that recruited a total of 7671 pregnant women were included. Only penicillins (odds ratio, 0.46; 95% confidence interval, 0.27-0.77) had significantly superior effectiveness for maternal chorioamnionitis. Clindamycin plus gentamicin reduced the risk of clinical chorioamnionitis, with borderline significance (odds ratio, 0.16; 95% confidence interval, 0.03-1.00). By contrast, clindamycin alone increased the risk of maternal infection. For cesarean delivery, no significant differences were noted among these regimens.
CONCLUSION
Penicillins remain the recommended antibiotic regimen for reducing maternal clinical chorioamnionitis. The alternative regimen includes clindamycin plus gentamicin. Clindamycin should not be used alone.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Clindamycin; Chorioamnionitis; Amoxicillin-Potassium Clavulanate Combination; Network Meta-Analysis; Anti-Bacterial Agents; Premature Birth; Erythromycin; Macrolides; Gentamicins; Cephalosporins
PubMed: 37094635
DOI: 10.1016/j.ajogmf.2023.100978 -
Expert Review of Anticancer Therapy Jul 2023Metastatic castrate resistant prostate cancer (mCPRC) remains an aggressive form of prostate cancer that no longer responds to traditional hormonal treatment alone.... (Review)
Review
INTRODUCTION
Metastatic castrate resistant prostate cancer (mCPRC) remains an aggressive form of prostate cancer that no longer responds to traditional hormonal treatment alone. Despite the advent of novel anti-androgen medications, many patients continue to progress, and as a result, there is a growing need for additional treatment options.
AREAS COVERED
Lutetium-177 (Lu) - PSMA-617 has become one of the new frontline treatment options for refractory metastatic castrate resistant prostate cancer after the failure of novel anti-androgen therapy and chemotherapy. Lu-177 has been used in real-world prospective trials and is now becoming utilized in newer phase III clinical trials. Here, we present a comprehensive overview of the current literature, covering retrospective studies, prospective studies, and clinical trials that established Lutetium-177-PSMA-617 (Lu-PSMA-617) for the treatment of mCRPC.
EXPERT OPINION
Lu - PSMA-617 has been approved for treatment of mCRPC based on positive phase III studies. While this treatment is tolerable and effective, biomarkers are necessary to determine which patients will benefit. In the future, radioligand treatments will likely be utilized in earlier lines of therapy and potentially in combination with other prostate cancer treatments.
Topics: Male; Humans; Prospective Studies; Prostatic Neoplasms, Castration-Resistant; Retrospective Studies; Radioisotopes; Prostate-Specific Antigen; Treatment Outcome
PubMed: 37194261
DOI: 10.1080/14737140.2023.2213892