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Journal of Neonatal-perinatal Medicine 2022Despite appropriate antibiotic therapy, the risk of mortality in neonatal sepsis still remains high. We conducted a systematic review to comprehensively evaluate... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Despite appropriate antibiotic therapy, the risk of mortality in neonatal sepsis still remains high. We conducted a systematic review to comprehensively evaluate different adjuvant therapies in neonatal sepsis in a network meta-analysis.
METHODS
We included randomized controlled trials (RCTs) and quasi-RCTs that evaluated adjuvant therapies in neonatal sepsis. Neonates of all gestational and postnatal ages, who were diagnosed with sepsis based on blood culture or sepsis screen were included. We searched MEDLINE, CENTRAL, EMBASE and CINAHL until 12th April 2021 and reference lists. Data extraction and risk of bias assessment were performed in duplicate. A network meta-analysis with bayesian random-effects model was used for data synthesis. Certainty of evidence (CoE) was assessed using GRADE.
RESULTS
We included 45 studies involving 6,566 neonates. Moderate CoE showed IVIG [Relative Risk (RR); 95% Credible Interval (CrI): 1.00; (0.67-1.53)] as an adjunctive therapy probably does not reduce all-cause mortality before discharge, compared to standard care. Melatonin [0.12 (0-0.08)] and granulocyte transfusion [0.39 (0.19-0.76)] may reduce mortality before discharge, but CoE is very low. The evidence is also very uncertain regarding other adjunctive therapies to reduce mortality before discharge. Pentoxifylline may decrease the duration of hospital stay [Mean difference; 95% CrI: -7.48 days (-14.50-0.37)], but CoE is very low.
CONCLUSION
Given the biological plausibility for possible efficacy of these adjuvant therapies and that the CoE from the available trials is very low to low except for IVIG, we need large adequately powered RCTs to evaluate these therapies in sepsis in neonates.
Topics: Humans; Infant, Newborn; Anti-Bacterial Agents; Immunoglobulins, Intravenous; Neonatal Sepsis; Network Meta-Analysis; Sepsis
PubMed: 36189501
DOI: 10.3233/NPM-221025 -
European Neurology 2022Increasing evidence has shown that oxidative stress is involved in the pathogenesis of Duchenne muscular dystrophy (DMD). Oxidative stress impairs muscle function,... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Increasing evidence has shown that oxidative stress is involved in the pathogenesis of Duchenne muscular dystrophy (DMD). Oxidative stress impairs muscle function, reduces regenerative capacity, and leads to atrophy and muscle weakness. The present study aimed to evaluate the effectiveness and safety of antioxidants in treatment of DMD patients.
METHODS
Medline, Embase, EBSCOhost, and Cochrane Library databases were searched using relevant keywords regarding DMD and antioxidants. The risk of bias for all included studies was assessed using the Cochrane risk of bias tool. The effectiveness of antioxidants in improving pulmonary function and muscle strength in DMD patients and their rate of adverse events was evaluated by meta-analysis.
RESULTS
A total of nine eligible studies were identified. Among these, two studies involving 85 patients compared idebenone with placebo. Pooled data showed a significant improvement in pulmonary function after idebenone treatment. Flavonoids- and omega 3-based compounds (FLAVOMEGA) significantly improved muscle strength. Two studies evaluated coenzyme Q10 (CoQ10) and reported clinical improvement in physical activity. The remaining four studies evaluated pentoxifylline, superoxide dismutase, vitamin E combination with penicillamine and penicillamine alone, respectively, and found no significant differences between the intervention and placebo groups, measured by pulmonary function, muscle strength, movement function, or quality of life. Most adverse events were mild, while the rates of dropout and serious adverse events were low with respect to antioxidants.
CONCLUSIONS
Idebenone appeared to be safe and effective in improving pulmonary function in DMD patients, while pentoxifylline, superoxide dismutase, penicillamine, or a combination of vitamin E with penicillamine did not show a significant therapeutic effect. CoQ10 and FLAVOMEGA might be beneficial in improving muscle strength or physical activity in DMD patients. However, additional trials with more participants are warranted in the future.
Topics: Antioxidants; Flavonoids; Humans; Muscular Dystrophy, Duchenne; Penicillamine; Pentoxifylline; Quality of Life; Superoxide Dismutase; Vitamin E
PubMed: 35697003
DOI: 10.1159/000525045 -
Advances in Radiation Oncology 2022Radiation therapy can affect normal tissues in patients with breast cancer, causing adverse effects such as fibrosis. Although there are several interventions for...
PURPOSE
Radiation therapy can affect normal tissues in patients with breast cancer, causing adverse effects such as fibrosis. Although there are several interventions for radiation-induced fibrosis, the efficacy of these procedures is still unclear. The purpose of this review is to evaluate the efficacy of interventions for radiation-induced fibrosis in patients with breast cancer.
METHODS AND MATERIALS
This is a systematic review of randomized clinical trials. Studies that compared any intervention for fibrosis to another intervention, placebo, or no intervention were included. Outcomes assessed were fibrosis, adverse events, quality of life, treatment adherence, pain, and functionality.
RESULTS
A total of 2501 publications were found, and 7 studies were selected because they met the inclusion criteria. The interventions for fibrosis were pentoxifylline and vitamin E, grape seed extract, kinesiotherapy, and endermotherapy. The results showed great heterogeneity in the treatment protocols for radiation-induced fibrosis in patients with breast cancer and in their evaluation metrics. The meta-analyses showed no benefit in using pentoxifylline and vitamin E compared with placebo or no intervention (standardized mean difference: -0.30; 95% confidence interval, -0.79 to 0.20; = .24 [very low evidence]) compared with placebo and vitamin E (standardized mean difference: -0.09; 95% confidence interval, -0.66 to 0.49; = .77 [moderate evidence]), respectively, assessed by the Late Effects Normal Tissue Task Force-Subjective, Objective, Management, and Analytic (LENT-SOMA) scoring scale.
CONCLUSIONS
The effectiveness of these interventions for the treatment of radiation-induced fibrosis in patients with breast cancer could not be determined. Although isolated studies show significant results favorable to the experimental groups, caution should be exercised in these findings because of the small number, small sample size, and high risk of bias presented by some of the included studies, which makes the recommendation for clinical practice still weak.
PubMed: 35647406
DOI: 10.1016/j.adro.2022.100912 -
Journal of Current Ophthalmology 2022To systematically review the role of antioxidants in management of patients with thyroid eye disease (TED). (Review)
Review
PURPOSE
To systematically review the role of antioxidants in management of patients with thyroid eye disease (TED).
METHODS
A literature search of the electronic databases was performed without restrictions on the date of publication till the end of March 2021, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Clinical trials, case-control studies, cohorts, case series, case reports, and experimental (including ) studies in the English language were included. The primary outcome in human studies was improvement in severity, activity scores, and/or quality of life scores. There was a decrease in the level of HO-dependent oxidative stress, Hyaluronic acid release, reactive oxygen species, cell proliferation, or antifibrotic/antiproliferative actions in the studies.
RESULTS
Out of 374 initially screened articles, 157 studies were selected, the full texts of 82 were reviewed, and 14 papers were finally included. There were 4 clinical and 10 studies from 1993 to 2018. While β-carotene, retinol, Vitamin E, Vitamin C, melatonin, resveratrol, N-acetyl-l-cysteine, and quercetin showed some efficacy in studies; allopurinol, nicotinamide, pentoxifylline, and selenium (Se) were effective in both clinical and experimental reports. Se was the only recommended antioxidant based on one high-level randomized controlled trial.
CONCLUSION
While different antioxidants could potentially be effective in the management of TED, no strong recommendation for any or combination of antioxidants could be made to be implemented in the daily practice.
PubMed: 35620378
DOI: 10.4103/joco.joco_266_21 -
European Review For Medical and... May 2022This systematic review and meta-analysis aimed to synthesize the latest evidence on pentoxifylline effect on the contrast-induced nephropathy (CIN) and whether the... (Meta-Analysis)
Meta-Analysis
The role of pentoxifylline in preventing contrast-induced nephropathy in coronary angiography/intervention - systematic review, meta-analysis, and meta-regression of randomized controlled trials.
OBJECTIVE
This systematic review and meta-analysis aimed to synthesize the latest evidence on pentoxifylline effect on the contrast-induced nephropathy (CIN) and whether the quality evidence is sufficient to make a definite conclusion MATERIALS AND METHODS: We performed a systematic literature search on topics that assesses pentoxifylline and CIN in coronary angiography/intervention up until 01 April 2021 using PubMed, Scopus, Embase, and hand-sampling. Primary outcome was CIN defined as ≥0.5 mg/dL or 25% rise in the SCr 48 h after procedure.
RESULTS
There were a total of 1142 subjects from 6 studies. There was no difference between pentoxifylline and control group in terms of serum creatinine at baseline (p=0.46) and after the procedure (p=0.33). The incidence of CIN was 51/571 (8.9%) in the pentoxifylline group and 61/571 (10.7%) in the control group. Pentoxifylline was not significantly associated with increase or decrease in the risk of CIN (RR 0.84 [0.59, 1.19], p=0.32; I2: 0%, p=0.89). Subgroup analysis for elective studies showed a non-significant result (RR 0.77 [0.47, 1.27], p=0.31; I2: 0%). Meta-regression analysis showed that the association between pentoxifylline and mortality was not affected by age (p=0.994), gender (reference: male, p=0.562), hypertension (p=0.336), diabetes (p=0.536), baseline serum creatinine (p=0.344), contrast used (p=0.431), and CIN incidence (p=0.521). GRADE Approach showed a low certainty of evidence for the effect estimate of pentoxifylline on CIN.
CONCLUSIONS
Our meta-analysis showed that pentoxifylline was not associated with the risk of CIN with low certainty of evidence. Hence, larger, multicentre, double-blind randomized controlled trials are required.
Topics: Contrast Media; Coronary Angiography; Creatinine; Humans; Kidney Diseases; Male; Pentoxifylline; Randomized Controlled Trials as Topic
PubMed: 35587083
DOI: 10.26355/eurrev_202205_28750 -
European Journal of Ophthalmology Nov 2022Radiation optic neuropathy (RON) generally follows radiation therapy that exceed 50 Gy to the visual axis and occurs within three years of therapy. Currently, there are... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Radiation optic neuropathy (RON) generally follows radiation therapy that exceed 50 Gy to the visual axis and occurs within three years of therapy. Currently, there are no universally accepted treatments or prophylaxis for RON. The review aimed to examine the efficacy of all treatments and prophylaxis for RON.
METHODS
MEDLINE, Embase, the Cochrane Library, and gray literature were searched to December 2020. Studies on treatment(s) and/or prophylaxis of RON were included. Results were meta-analyzed using a random-effects model. Primary outcomes included the proportions of patients who experienced improvement, no change, or worsening of visual acuity (VA) for each treatment. Secondary outcome was the incidence of RON for studies on prophylaxis.
RESULTS
Overall, 50 studies (n = 5397) were included. Meta-analysis (n = 1752) showed significantly lower incidence of RON in patients who underwent intravitreal anti-VEGF prophylaxis compared to control (RR 0.64, 95%CI [0.48, 0.86]) for uveal melanoma. Intravitreal anti-VEGF injections (n = 68), hyperbaric oxygen therapy alone (n = 14), and pentoxifylline (n = 5) resulted in improved or stable vision ≤1 logMAR in 54.5%, 42.9%, and 40.0% of patients, respectively. Systemic corticosteroids (n = 82), anticoagulants (n = 12), and systemic bevacizumab (n = 7) showed improved or stable vision ≤1 logMAR in 17.1%, 33.3%, and 14.3% of patients, respectively. Overall risk of bias was low, but evidence was limited to retrospective studies.
CONCLUSION
Intravitreal anti-VEGF injections reduced incidence of RON in irradiated uveal melanoma patients. Systemic corticosteroids, systemic bevacizumab, and warfarin alone are likely ineffective treatments. Early hyperbaric oxygen therapy and intravitreal anti-VEGF injections were most effective among those investigated and require further investigation.
Topics: Adrenal Cortex Hormones; Angiogenesis Inhibitors; Anticoagulants; Bevacizumab; Humans; Intravitreal Injections; Melanoma; Optic Nerve Diseases; Pentoxifylline; Ranibizumab; Retrospective Studies; Uveal Neoplasms; Vascular Endothelial Growth Factor A; Warfarin
PubMed: 35262423
DOI: 10.1177/11206721221085409 -
Pain Reports 2022Pain is highly prevalent in patients with cancer-nearly 40% report moderate-severe pain, which is commonly treated with opioids. Increasing cancer survivorship, opioid... (Review)
Review
Pain is highly prevalent in patients with cancer-nearly 40% report moderate-severe pain, which is commonly treated with opioids. Increasing cancer survivorship, opioid epidemics in some regions of the world, and limited opioid access in other regions have focused attention on nonopioid treatments. Given the limitations of monotherapy, combining nonopioids-such as antiepileptics and antidepressants-have shown promise in noncancer pain. This review seeks to evaluate efficacy of nonopioid combinations for cancer-related pain. Systematic searches of PubMed, EMBASE, and Cochrane CENTRAL were conducted for double-blind, randomized, controlled trials comparing a nonopioid combination with at least one of its components and/or placebo. This search yielded 4 randomized controlled trials, published between 1998 and 2019 involving studies of (1) imipramine + diclofenac; (2) mitoxantrone + prednisone + clodronate; (3) pentoxifylline + tocopherol + clodronate; and (4) duloxetine + pregabalin + opioid. In the first 3 of these trials, trends favouring combination efficacy failed to reach statistical significance. However, in the fourth trial, duloxetine + pregabalin + opioid was superior to pregabalin + opioid. This review illustrates recognition for the need to evaluate nonopioid drug combinations in cancer pain, although few trials have been published to date. Given the growing practice of prescribing more than 1 nonopioid for cancer pain and the need to expand the evidence base for rational combination therapy, more high-quality trials in this area are needed.
PubMed: 35261931
DOI: 10.1097/PR9.0000000000000995 -
Frontiers in Pharmacology 2021Pentoxifylline (PTX) is a member of methylxanthine chemicals and a type of non-selective phosphodiesterase-5 inhibitors, which has been used in male infertility... (Review)
Review
Pentoxifylline (PTX) is a member of methylxanthine chemicals and a type of non-selective phosphodiesterase-5 inhibitors, which has been used in male infertility treatment to improve sperm quality and erectile dysfunction (ED) treatment. Mutually tight associations existed between ED and male infertility. Using PTX might kill two birds with one stone by improving sperm quality and erectile function in infertile men with ED. PubMed, Cochrane Library, EMBASE, and Web of Science were searched by October 2021. Based on available evidence from observational studies and randomized-controlled trials (RCTs), we conducted a systematic review to summarize the efficacy and safety of PTX in treating ED and male infertility. The protocol of the article was registered and updated in PROSPERO (CRD42021291396). From 202 records, eight studies (7 RCTs) evaluating the role of PTX in ED and three studies (2 RCTs) assessing the efficacy of PTX in male infertility were included in the systematic review. Three studies (100.00%) and two studies (100.00%) reported the beneficial role of PTX in improving sperm progressive motility and normal sperm morphology rate, respectively. In contrast, only one study (33.33%) indicated the favorable role of PTX in enhancing sperm concentration. As for ED, three (60.00%) studies supported the treatment role of PTX alone in ED, and two studies (66.67%) favored the combination use of PTX and selective PDE5Is compared with selective PDE5Is alone. Safety analysis showed that PTX was a well-tolerated drug in ED and male infertility treatment. Given the association between ED and male infertility and satisfying findings from available evidence, PTX administration for the simultaneous treatment of poor sperm quality and mild ED in infertile men will highly enhance the treatment compliance. However, the finding should be treated carefully until validated by further studies.
PubMed: 35095501
DOI: 10.3389/fphar.2021.789787 -
Annals of Plastic Surgery Dec 2021Partial flap necrosis is a common complication after surgery. McFarlane flap model has been used for assessment of various agents' effects on random flap survival. The... (Meta-Analysis)
Meta-Analysis
Standardization of the Rat Dorsal Random Pattern (McFarlane) Flap Model and Evaluation of the Pharmacological Agents Aiming to Salvage Partial Flap Necrosis: A Systematic Review and a Meta-analysis.
INTRODUCTION
Partial flap necrosis is a common complication after surgery. McFarlane flap model has been used for assessment of various agents' effects on random flap survival. The aim of this study was to review the methodology of studies using this flap model and reveal the most successful agents.
MATERIALS AND METHODS
PubMed, Scopus, and Web of Science databases were screened for words "McFarlane flap," "flap survival," and ("flap" and "rat") by using time limits between 1965 and 2019. A total of 71 original articles were reviewed. Dimensions and base (cranial/caudal) of the flap, treatment protocol, follow-up period, and survival rates were extracted. Modified survival rates were calculated. Coefficients of variation of cranial/caudally based control group flaps and most commonly used flap models were calculated to assess interstudy variability.
RESULTS
A total of 165 different treatment regimens were studied. One-hundred twelve regimens (67.9%) were found to increase flap survival. Most common flap dimensions were 9 cm × 3 cm, followed by 10 cm × 3 cm, 8 cm × 2 cm and 6 cm × 2 cm. Studies using caudally based flaps showed less interstudy variability, but survival rates were similar. Pentoxifylline, sildenafil, chlorpromazine, phenoxybenzamine, and phentolamine were reported to be successful in multiple studies.
CONCLUSIONS
There are numerous agents found to be effective for treatment of partial flap necrosis, but further clinical research is needed. To overcome standardization problems, use of commonly used flap dimensions with a caudal base and interpretation of results after 7 days of follow-up seems appropriate.
Topics: Animals; Graft Survival; Necrosis; Rats; Reference Standards; Salvage Therapy; Surgical Flaps
PubMed: 34818287
DOI: 10.1097/SAP.0000000000002919 -
The Cochrane Database of Systematic... Nov 2021Acute bacterial meningitis is a bacterial infection of the membranes that surround and protect the brain, known as the meninges. The primary therapy for bacterial... (Review)
Review
BACKGROUND
Acute bacterial meningitis is a bacterial infection of the membranes that surround and protect the brain, known as the meninges. The primary therapy for bacterial meningitis is antibiotics and corticosteroids. Although these therapies significantly improve outcomes, bacterial meningitis still has a high risk of death and a high risk of neurological sequelae in survivors. New adjuvant therapies are needed to further reduce the risk of death and neurological sequelae in bacterial meningitis.
OBJECTIVES
To assess the effects of non-corticosteroid adjuvant pharmacological therapies for mortality, hearing loss, and other neurological sequelae in people with acute bacterial meningitis.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, CINAHL, and LILACS databases and ClinicalTrials.gov and WHO ICTRP trials registers up to 30 September 2021, together with reference checking, citation searching, and contact with study authors to identify additional studies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of any pharmacological adjuvant therapy for acute bacterial meningitis.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed and extracted data on methods, participants, interventions, and outcomes. We assessed risk of bias of studies with the Cochrane risk of bias tool and the certainty of the evidence using the GRADE approach. We presented results using risk ratios (RR) and 95% confidence intervals (CI) when meta-analysis was possible. All other results are presented in a narrative synthesis.
MAIN RESULTS
We found that five different adjuvant therapies have been tested in RCTs for bacterial meningitis. These include paracetamol (3 studies, 1274 participants who were children); immunoglobulins (2 studies, 49 participants; one study included children, and the other adults); heparin (1 study, 15 participants who were adults); pentoxifylline (1 study, 57 participants who were children); and a mixture of succinic acid, inosine, nicotinamide, and riboflavin mononucleotide (1 study, 30 participants who were children). Paracetamol may make little or no difference to mortality (paracetamol 35.2% versus placebo 37.4%, 95% CI 30.3% to 40.8%; RR 0.94, 95% CI 0.81 to 1.09; 3 studies, 1274 participants; I² = 0%; low certainty evidence); hearing loss (RR 1.04, 95% CI 0.80 to 1.34; 2 studies, 901 participants; I² = 0%; low certainty evidence); neurological sequelae other than hearing loss (RR 1.56, 95% CI 0.98 to 2.50; 3 studies, 1274 participants; I² = 60%; low certainty evidence); and severe hearing loss (RR 0.96, 95% CI 0.67 to 1.36; 2 studies, 901 participants; I² = 0%; low certainty evidence). Paracetamol may lead to slightly more short-term neurological sequelae other than hearing loss (RR 1.99, 95% CI 1.40 to 2.81; 2 studies, 1096 participants; I² = 0%; low certainty evidence) and slightly more long-term neurological sequelae other than hearing loss (RR 2.32, 95% CI 1.34 to 4.04; 2 studies, 901 participants; I² = 0%; low certainty evidence). No adverse events were reported in either group in any of the paracetamol studies (very low certainty evidence). Two paracetamol studies had a low risk of bias in most domains, and one had low or unclear risk of bias in all domains. We judged the certainty of evidence to be low for mortality due to limitations in study design (unclear risk of bias in at least one domain and imprecision (high level of uncertainty in absolute effects), and low for all other outcomes due to limitations in study design (unclear risk of bias in at least one domain), and imprecision (low sample size and few events) or inconsistency in effect estimates (heterogeneity). We were not able to perform meta-analysis for any of the other adjuvant therapies due to the limited number of included studies. It is uncertain whether immunoglobulins, heparin, or pentoxifylline improves mortality outcomes due to the very low certainty of the evidence. Zero adverse events were reported for immunoglobulins (very low certainty evidence), and allergic reactions occurred at a rate of 3.3% in participants receiving a mixture of succinic acid, inosine, nicotinamide, and riboflavin mononucleotide (intervention group) (very low certainty evidence). None of our other outcomes (hearing loss, neurological sequelae other than hearing loss, severe hearing loss, and short-term or long-term neurological sequelae other than hearing loss) were reported in these studies, and all of these studies were judged to have a high risk of bias. All reported outcomes for all included adjuvant therapies, other than paracetamol, were graded as very low certainty of evidence due to limitations in study design (unclear or high risk of bias in at least four domains) and imprecision (extremely low sample size and few events).
AUTHORS' CONCLUSIONS
Few adjuvant therapies for bacterial meningitis have been tested in RCTs. Paracetamol may make little or no difference to mortality, with a high level of uncertainty in the absolute effects (low certainty evidence). Paracetamol may make little or no difference to hearing loss, neurological sequelae other than hearing loss, and severe hearing loss (all low certainty evidence). Paracetamol may lead to slightly more short-term and long-term neurological sequelae other than hearing loss (both outcomes low certainty evidence). There is insufficient evidence to determine whether any of the adjuvant therapies included in this review (paracetamol, immunoglobulins, heparin, pentoxifylline, or a mixture of succinic acid, inosine, nicotinamide, and riboflavin mononucleotide) are beneficial or detrimental in acute bacterial meningitis.
Topics: Acetaminophen; Adrenal Cortex Hormones; Adult; Anti-Bacterial Agents; Child; Hearing Loss; Humans; Meningitis, Bacterial
PubMed: 34813078
DOI: 10.1002/14651858.CD013437.pub2