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Antimicrobial Agents and Chemotherapy Aug 2022To systematically evaluate the relationships between vancomycin trough serum concentrations and clinical outcomes in children using meta-analysis. Several databases,... (Meta-Analysis)
Meta-Analysis
To systematically evaluate the relationships between vancomycin trough serum concentrations and clinical outcomes in children using meta-analysis. Several databases, including PubMed, Elsevier, Web of Science, EMBASE, Medline, clinicaltrials.gov, the Cochrane Library, and three Chinese databases (Wanfang Data, China National Knowledge Infrastructure, and SINOMED), were comprehensively searched to obtain research articles on vancomycin use in children from inception through December 2021. All studies were screened and evaluated using the Cochrane systematic review method. Then, the feature information was extracted for meta-analysis. The evaluated results included clinical efficacy, vancomycin-associated nephrotoxicity, hepatotoxicity, ototoxicity, mortality, and microbial clearance. A total of 35 studies involving 4820 children were included in the analysis. The meta-analysis showed that compared with children with vancomycin trough concentrations <10 μg/mL, those with vancomycin trough concentrations ≥10 μg/mL had a higher clinical efficacy rate [OR: 2.23, 95% CI: 1.29 to 3.84, = 0.004] and higher incidences of nephrotoxicity [OR: 2.76, 95% CI: 1.51 to 5.07, = 0.001], ototoxicity [OR: 1.87, 95% CI: 1.08 to 3.23, = 0.02] and microbial clearance [OR: 2.36, 95% CI: 1.53 to 3.64, = 0.0001]. All-cause mortality [OR: 1.07, 95% CI: 0.45 to 2.53, = 0.88] and hepatotoxicity [OR: 0.84, 95% CI: 0.46 to 1.53, = 0.57] were similar between the two groups. Subgroup analysis showed that compared with children with vancomycin trough concentrations of 10 to 15 μg/mL, those with vancomycin trough concentrations >15 μg/mL had a higher incidence of nephrotoxicity [OR: 2.64, 95% CI: 1.28 to 5.43, = 0.008], but there was no significant difference in clinical efficacy [OR: 0.85, 95% CI: 0.30 to 2.44, = 0.76]. A vancomycin trough concentration of 10 to 15 μg/mL can improve clinical efficacy in children. Additionally, avoidance of trough concentrations >15 μg/mL can reduce the incidence of adverse reactions.
Topics: Anti-Bacterial Agents; Chemical and Drug Induced Liver Injury; Child; Humans; Ototoxicity; Renal Insufficiency; Retrospective Studies; Vancomycin
PubMed: 35862741
DOI: 10.1128/aac.00138-22 -
International Journal of Particle... 2021To evaluate the clinical outcomes and treatment related toxicities of charged particle-based re-irradiation (reRT; protons and carbon ions) for the definitive management...
PURPOSE
To evaluate the clinical outcomes and treatment related toxicities of charged particle-based re-irradiation (reRT; protons and carbon ions) for the definitive management of recurrent or second primary skull base and head and neck tumors.
MATERIALS AND METHODS
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were applied for the conduct of this systematic review. Published work in English language evaluating the role of definitive charged particle therapies in the clinical setting of reRT for recurrent or second primary skull base and head and neck tumors were eligible for this analysis.
RESULTS
A total of 26 original studies (15 protons, 10 carbon ions, and 1 helium/neon studies) involving a total of 1,118 patients (437 with protons, 670 with carbon ions, and 11 with helium/neon) treated with curative-intent charged particle reRT were included in this systematic review. All studies were retrospective in nature, and the majority of them (n=23, 88 %) were reported as single institution experiences (87% for protons, and 90% for carbon ion-based studies). The median proton therapy reRT dose was 64.5 Gy (RBE 1.1) (range, 50.0 - 75.6 Gy ), while the median carbon ion reRT dose was 53.8 Gy (RBE 2.5 - 3.0) (range, 44.8 - 60 Gy ). Induction and/or concurrent chemotherapy was administered to 232 (53%) of the patients that received a course of proton reRT, and 122 (18%) for carbon ion reRT patients. ReRT with protons achieved 2-year local control rates ranging from 50% to 86%, and 41% to 92% for carbon ion reRT. The 2-year overall survival rates for proton and carbon ion reRT ranged from 33% to 80%, and 50% to 86% respectively. Late ≥ G3 toxicities ranged from 0% to 37%, with brain necrosis, ototoxicity, visual deficits, and bleeding as the most common complications. Grade 5 toxicities for all treated patients occurred in 1.4% (n= 16/1118) with fatal bleeding as the leading cause.
CONCLUSIONS
Based on current data, curative intent skull base and head and neck reRT with charged particle radiotherapy is feasible and safe in well-selected cases, associated with comparable or potentially improved local control and toxicity rates compared to historical reRT studies using photon radiotherapy. Prospective multi-institutional studies reporting oncologic outcomes, toxicity, and dosimetric treatment planning data are warranted to further validate these findings and to improve the understanding of the clinical benefits of charged particle radiotherapy in the reRT setting.
PubMed: 34285942
DOI: 10.14338/IJPT-20-00064.1 -
Brazilian Journal of Otorhinolaryngology 2022Platinum-based chemotherapeutics play an important role in the treatment of cancer at different levels and are the most cited ototoxic agents when scientific evidence is... (Review)
Review
INTRODUCTION
Platinum-based chemotherapeutics play an important role in the treatment of cancer at different levels and are the most cited ototoxic agents when scientific evidence is analyzed.
OBJECTIVE
To present scientific evidence based on a systematic literature review, PRISMA, in order to systematize information on the ototoxic effects of using antineoplastic drugs.
METHODS
For the selection of studies, the combination based on the Medical Subject Heading Terms (MeSH) was used. The Medline (Pubmed), LILACS, SciELO, SCOPUS, WEB OF SCIENCE and BIREME databases were used, without restriction of language, period, and location. Evaluation of the quality of the articles was carried out, which included articles with a minimum score of 6 in the modified scale of the literature. The designs of the selected studies were descriptive, cohort, and cross-sectional, which were related to the research objective.
RESULTS
Three articles were included in this systematic review. The ototoxicity caused by cisplatin alone varied from 45% to 83.3%, while that caused by the use associated with carboplatin varied from 16.6% to 75%. There was a significant variation in the cumulative doses of these antineoplastic agents, both in isolated and in combination. Auditory changes, especially at high frequencies, were evident after completion of treatment.
CONCLUSION
Auditory changes after the use of platinum-based antineoplastic drugs were found, however, there was an important heterogeneity regarding the frequency of ototoxicity and the cumulative dose of the drugs used.
Topics: Antineoplastic Agents; Cisplatin; Cross-Sectional Studies; Hearing Loss; Humans; Ototoxicity
PubMed: 33757754
DOI: 10.1016/j.bjorl.2021.02.008 -
The Journal of International Advanced... Jan 2021Sudden sensorineural hearing loss (SSNHL) is defined as hearing loss of ≥30 dB in one or both ears, developing within 3 days, affecting ≥3 contiguous frequencies. It...
Sudden sensorineural hearing loss (SSNHL) is defined as hearing loss of ≥30 dB in one or both ears, developing within 3 days, affecting ≥3 contiguous frequencies. It is rare in children, but if untreated can cause significant morbidity. During the critical developmental period, it may cause lifelong social, behavioral, and mental sequelae. Currently, little guidance exists on prognosis and management within a pediatric population. A systematic literature review of pediatric SSNHL on PubMed, EMBASE, and the Cochrane CENTRAL database was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations. A total of 620 papers met the Medical Subject Headings criteria, of which 14 met analysis criteria-13 were level 4 and 1 was level 2b evidence. A population of 732 individuals was analyzed. Most reported cases of pediatric SSNHL were idiopathic. Other etiologies included viral infection, trauma, ototoxic drugs, and structural abnormalities. Recovery was defined as any improvement in hearing after the initial loss, from "slight" to "complete." Recovery ranged from 20% to 100%, with a pooled rate of 56%. Systemic steroids were the mainstay of treatment, although salvage intratympanic steroid therapy had a role after the failure of systemic steroids. Children with bilateral SSNHL had poorer outcomes than those with unilateral loss, with 29% showing improvement. Two studies reported outcomes with no treatment, for which recovery rate was 7%. This analysis of SSNHL shows that 61% of children with unilateral and 29% of children with bilateral SSNHL demonstrate some recovery, a worse prognosis than adults. Multiple treatment regimens exist, although comparison is challenging owing to inconsistently reported improvement parameters.
Topics: Adolescent; Child; Hearing; Hearing Loss, Sensorineural; Hearing Loss, Sudden; Humans; Pharmaceutical Preparations; Retrospective Studies
PubMed: 33605224
DOI: 10.5152/iao.2020.8902 -
Orthopaedics & Traumatology, Surgery &... Sep 2022The application of antibiotics loaded bone cement (ALBC) in the revision of failed total knee arthroplasty (TKA) has been widely accepted to reduce risk of... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
The application of antibiotics loaded bone cement (ALBC) in the revision of failed total knee arthroplasty (TKA) has been widely accepted to reduce risk of peri-prosthetic infection. However, the prophylactic use of ALBC in primary TKA remains controversial. This study was aimed to identify the prophylactic effect on peri-prosthetic infection and safety of ALBC in primary TKA.
HYPOTHESIS
The application of ALBC could reduce the risk of peri-prosthetic infection in primary TKA.
MATERIALS AND METHODS
Electronic platforms including PubMed, EMBASE, and CENTRAL were retrieved to identify studies comparing outcomes of prophylactic ALBC and plain cement in primary TKA. For outcomes reported as dichotomous variable and continuous variable, risk ratio (RR) and weighted mean difference (WMD) as well as their 95% confidence intervals (95% CI) were selected as the effect sizes for pooling. While for those outcomes reported the adjusted effect sizes such as odds ratio (OR, derived from multivariate logistic regression), and hazard ratio (HR, derived from multivariate COX proportional hazard model), the reported effect sizes were selected for pooling.
RESULTS
A total of 17 studies with 2,074,844 patients (1,093,920 in ALBC group and 980,924 in plain cement group) were eligible for final inclusion. No significant difference was found between ALBC and plain cement groups both for the unadjusted (RR=1.02, 95% CI: 0.86∼1.21, p=0.832) and adjusted (OR=0.94, 95% CI: 0.76∼1.17, p=0.596) peri-prosthetic infection rate. ALBC application was related to significantly increased length of hospital stay (WMD=0.13, 95% CI: 0.10∼0.17, p<0.001). There was no significance on the difference of operation related adverse events between two groups (RR=1.31, 95% CI: 0.68∼2.52, p=0.420). Significantly increased risks of acute renal failure and readmission, and temporarily increased ototoxicity in ALBC group were reported in one of the primary study.
DISCUSSION
There is no sufficient evidence supporting decreased peri-prosthetic infection rate with ALBC application in primary TKA. What's more, it must be taken into consideration about the safety and added cost of additional impregnated antibiotics.
LEVEL OF EVIDENCE
III; meta-analysis.
Topics: Anti-Bacterial Agents; Arthroplasty, Replacement, Knee; Bone Cements; Humans; Length of Stay; Prosthesis-Related Infections
PubMed: 35552043
DOI: 10.1016/j.otsr.2022.103295 -
The Indian Journal of Tuberculosis Apr 2019Second-line injectables (SLIs) form an essential class of agents in the treatment of drug resistant (DR) tuberculosis (TB). However, their use is sometimes limited due...
Second-line injectables (SLIs) form an essential class of agents in the treatment of drug resistant (DR) tuberculosis (TB). However, their use is sometimes limited due to serious adverse events like ototoxicity and hearing loss, leading to permanent hearing loss if SLIs are continued. Globally as well as in India a wide variation in incidence of ototoxicity/hearing loss has been reported in patients with DR-TB. In this systematic analysis, we attempt to ascertain the ototoxicity of SLIs in Indian patients with multidrug resistant tuberculosis (MDR-TB) wherein ototoxicity onset was assessed using audiometry performed at both pre- and post-SLI treatment initiation. Twenty two studies were identified based on the inclusion criteria. Ototoxicity was observed in 10.12% [349/3447] patients within 3.8 ± 2.6 months of treatment initiation when the ototoxicity was assessed either with or without audiometry assessment. Only five studies reported ototoxicity assessment with PTA at both pre- and post-SLI initiation and ototoxicity was observed in 27.01% (121/448) patients in these five studies. Sensorineural loss was observed in three studies (high frequency loss: capreomycin, 25.0% [1/4 patients]; amikacin, 19.7% [12/61]; kanamycin, 13.3% [22/166]; streptomycin, 11.8% [2/17]; flat loss: amikacin, 8.2% [5/61]; streptomycin, 5.9% [1/17]; kanamycin 4.8% [8/166]). Most of the patients experiencing ototoxicity were managed by discontinuing (49.6% [120/242]) or replacing SLI treatment (40.8% [49/120]). The study identified high prevalence of ototoxicity in Indian patients with DR-TB treated with SLI when ototoxicity was monitored regularly using PTA (27.01%), warranting a need to develop unified guidelines for monitoring ototoxicity, improving physician awareness and educating patients/caregivers for reporting symptoms of hearing loss.
Topics: Antitubercular Agents; Capreomycin; Hearing Loss; Humans; India; Injections, Intramuscular; Ototoxicity; Tuberculosis, Multidrug-Resistant
PubMed: 31151497
DOI: 10.1016/j.ijtb.2019.04.007 -
Advances in Radiation Oncology 2023The aim of this study was to comprehensively review all studies examining clinical outcomes of craniospinal irradiation with proton radiotherapy for medulloblastoma (MB)... (Review)
Review
PURPOSE
The aim of this study was to comprehensively review all studies examining clinical outcomes of craniospinal irradiation with proton radiotherapy for medulloblastoma (MB) to determine whether theoretical dosimetric advantages have translated into superior clinical outcomes (including survival and toxicities) compared with traditional photon-based techniques.
METHODS AND MATERIALS
We performed a systematic review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Articles reporting on clinical outcomes of pediatric and/or adult patients with MB treated with proton radiotherapy were included. Evidence quality was assessed using a modified Newcastle Ottawa scale and GRADE score.
RESULTS
Thirty-five studies were included, with a total of 2059 patients reported (representing an estimated 630-654 unique patients). None of the studies were randomized, 12 were comparative, 9 were prospective, 3 were mixed, and 22 were retrospective. Average mean/median follow-up was 5.0 years (range, 4 weeks to 12.6 years). The majority of studies (n = 19) reported on treatment with passive scatter proton beams exclusively. Average study quality was 6.0 out of 9 (median, 6; standard deviation, 1.6). Nine studies scored ≥8 out of 9 on the modified Newcastle Ottawa Scale; an overall "moderate" GRADE score was assigned. Well-designed comparative cohort studies with adequate follow-up demonstrate superior neurocognitive outcomes, lower incidence of hypothyroidism (23% vs 69%), sex hormone deficiency (3% vs 19%), greater heights, and reduced acute toxicities in patients treated with protons compared to photons. Overall survival (up to 10 years), progression-free survival (up to 10 years), brain stem injury, and other endocrine outcomes were similar to those reported for photon radiation. There was insufficient evidence to make conclusions on endpoints of quality of life, ototoxicity, secondary malignancy, alopecia, scoliosis, cavernomas, and cerebral vasculopathy.
CONCLUSIONS
Moderate-grade evidence supports proton radiotherapy as a preferred treatment for craniospinal irradiation of MB based on equivalent disease control and comparable-to-improved toxicity versus photon beam radiation therapy.
PubMed: 37008255
DOI: 10.1016/j.adro.2023.101189 -
Revista Da Associacao Medica Brasileira... 2021To present scientific evidence based on a systematic review of the literature (PRISMA), aiming to systematize evidence of the ototoxic effects of hydroxychloroquine...
OBJECTIVE
To present scientific evidence based on a systematic review of the literature (PRISMA), aiming to systematize evidence of the ototoxic effects of hydroxychloroquine (HCQ).
METHODS
The studies were selected using a combination based on the Medical Subject Headings (MeSH). The databases searched were MEDLINE (PubMed), LILACS, SciELO, and BIREME, encompassing articles from January 2010 to May 2020, with no restrictions of language and place of publication.
RESULTS
A total of 148 articles with the potential to be included were retrieved. Of these, two answered the research question, which consisted of seeking evidence of the ototoxic effects of hydroxychloroquine. These studies scored 11 in their quality assessment with the modified protocol by Pithon et al.13.
CONCLUSIONS
The studies reported possible ototoxicity of HCQ. Audiovestibular changes, such as hearing loss, peripheral vestibular syndrome, and tinnitus were evidenced in patients submitted to HCQ. The improvement in the audiological examinations and the regression in the vestibular syndrome after stopping the treatment with HCQ are strong arguments in favor of the ototoxicity caused by this medication. However, there are still divergences about the relationship between ototoxic effects and the use of HCQ.
Topics: Hearing Loss; Humans; Hydroxychloroquine; Ototoxicity
PubMed: 34259762
DOI: 10.1590/1806-9282.67.Suppl1.20200677 -
Current Medicinal Chemistry May 2023Ototoxicity is one of the major adverse effects of cisplatin therapy which restrict its clinical application. Alpha-lipoic acid administration may mitigate...
PURPOSE
Ototoxicity is one of the major adverse effects of cisplatin therapy which restrict its clinical application. Alpha-lipoic acid administration may mitigate cisplatin-induced ototoxicity. In the present study, we reviewed the protective potentials of alpha-lipoic acid against the cisplatin-mediated ototoxic adverse effects.
METHODS
Based on the PRISMA guideline, we performed a systematic search for the identification of all relevant studies in various electronic databases up to June 2022. According to the inclusion and exclusion criteria, the obtained articles (n=59) were screened and 13 eligible articles were finally included in the present study.
RESULTS
The findings of in-vitro experiments showed that cisplatin treatment significantly reduced the auditory cell viability in comparison with the control group; nevertheless, the alpha-lipoic acid co-administration protected the cells against the reduction of cell viability induced by cisplatin treatment. Moreover, the in-vivo results of the auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) tests revealed a decrease in DPOAE and an increase in ABR threshold of cisplatin-injected animals; however, it was shown that alpha-lipoic acid co-treatment had an opposite pattern on the evaluated parameters. Other findings demonstrated that cisplatin treatment could significantly induce the biochemical and histopathological alterations in inner ear cells/tissue; in contrast, alpha-lipoic acid co-treatment ameliorated the cisplatin-mediated biochemical and histological changes.
CONCLUSION
The findings of audiometry, biochemical parameters, and histological evaluation showed that alpha-lipoic acid co-administration alleviates the cisplatin-induced ototoxicity. The protective role of alpha-lipoic acid against the cisplatin-induced ototoxicity can be due to different mechanisms of anti-oxidant, anti-apoptotic, anti-inflammatory activities, and regulation of cell cycle progression.
PubMed: 37165582
DOI: 10.2174/0929867330666230509162513 -
Annals of Oncology : Official Journal... Nov 2017Testicular germ-cell tumors (GCT) are highly curable. A multidisciplinary approach, including cisplatin-based chemotherapy has resulted in cure in the majority of... (Review)
Review
CONTEXT
Testicular germ-cell tumors (GCT) are highly curable. A multidisciplinary approach, including cisplatin-based chemotherapy has resulted in cure in the majority of patients with GCT. Thus, the life expectancy of survivors will extend to many decades post-diagnosis. Late treatment toxicities associated with cisplatin-based chemotherapy may impact their future health.
OBJECTIVE
To systematically evaluate evidence regarding the long-term toxicity of cisplatin in GCT survivors.
EVIDENCE ACQUISITION
We carried out a critical review of PubMed/Medline in February 2017 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Identified reports were reviewed according to the Consolidated Standards of Reporting Trials (CONSORT) criteria. Eighty-three publications were selected for inclusion in this analysis.
EVIDENCE SYNTHESIS
Included reports evaluated long-term toxicities of cisplatin-based chemotherapy in GCT survivors. Studies reporting neuro- and ototoxicity, secondary malignancies, cardiovascular, renal and pulmonary toxicities, hypogonadism and infertility were found. Seven studies (8%) reported genetic underpinnings of long-term toxicities and 3 (4%) and 14 (19%) studies correlated long-term toxicities with circulating platinum levels and cumulative dose of cisplatin, respectively. Significant risks for long-term toxicities associated with cisplatin and platinum-based regimens were reported. The cumulative dose of cisplatin and circulating platinum were reported as risk factors. Several single-nucleotide polymorphisms identified patients susceptible to cisplatin compared with wild-type individuals.
CONCLUSIONS
GCT survivors cured with cisplatin-based chemotherapy are at risk for long-term side-effects. Detection of single-nucleotide polymorphisms could be a valuable tool for predicting long-term toxicities.
PATIENT SUMMARY
Herein, this article summarizes the available evidence of long-term toxicity of cisplatin-based chemotherapy in GCT survivors and provide insights from Indiana University.
Topics: Antineoplastic Agents; Cisplatin; Humans; Neoplasms, Germ Cell and Embryonal; Neoplasms, Second Primary; Prognosis; Risk Factors; Survivors
PubMed: 29045502
DOI: 10.1093/annonc/mdx360