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Frontiers in Pharmacology 2024Urothelial carcinoma (UC) is a refractory disease for which achieving satisfactory outcomes remains challenging with current surgical interventions. Antibody-drug...
Urothelial carcinoma (UC) is a refractory disease for which achieving satisfactory outcomes remains challenging with current surgical interventions. Antibody-drug conjugates (ADCs) are a novel class of targeted therapeutics that have demonstrated encouraging results for UC. Although there is a limited number of high-quality randomized control trials (RCTs) examining the use of ADCs in patients with UC, some prospective non-randomized studies of interventions (NRSIs) provide valuable insights and pertinent information. We aim to assess the efficacy and safety of ADCs in patients with UC, particularly those with locally advanced and metastatic diseases. A systematic search was conducted across PubMed, Embase, the Cochrane Library, and Web of Science databases to identify pertinent studies. Outcomes, such as the overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), adverse events (AEs), and treatment-related adverse events (TRAEs), were extracted for further analyses. Twelve studies involving 1,311 patients were included in this meta-analysis. In terms of tumor responses, the pooled ORR and DCR were 40% and 74%, respectively. Regarding survival analysis, the pooled median PFS and OS were 5.66 months and 12.63 months, respectively. The pooled 6-month PFS and OS were 47% and 80%, while the pooled 1-year PFS and OS were 22% and 55%, respectively. The most common TRAEs of the ADCs were alopecia (all grades: 45%, grades ≥ III: 0%), decreased appetite (all grades: 34%, grades ≥ III: 3%), dysgeusia (all grades: 40%, grades ≥ III: 0%), fatigue (all grades: 39%, grades ≥ III: 5%), nausea (all grades: 45%, grades ≥ III: 2%), peripheral sensory neuropathy (all grades: 37%, grades ≥ III: 2%), and pruritus (all grades: 32%, grades ≥ III: 1%). The meta-analysis in this study demonstrates that ADCs have promising efficacies and safety for patients with advanced or metastatic UC. https://www.crd.york.ac.uk/prospero/, identifier: CRD42023460232.
PubMed: 38933670
DOI: 10.3389/fphar.2024.1377924 -
European Review For Medical and... Apr 2024Dysgeusia is characterized by a loss of taste perception, leading to malnutrition. This situation affects inflammatory conditions such as respiratory and neurological... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Dysgeusia is characterized by a loss of taste perception, leading to malnutrition. This situation affects inflammatory conditions such as respiratory and neurological conditions, obesity, cancer, chemotherapy, aging, and many others. To date, there is not much information on the prevalence and risk of dysgeusia in an inflammatory condition; also, it is unclear which flavor is altered.
MATERIALS AND METHODS
We systematically searched three databases from January 2018 to January 2023. Participants were children, adults, or elderly persons with an inflammatory condition and evaluated taste loss. A random effects model was used for statistical analysis to calculate the pooled odds ratio with its corresponding 95.0% confidence interval to estimate the probability of taste alteration (dysgeusia) in an inflammatory condition.
RESULTS
The data allowed us to conduct a systematic review, including 63 original articles and 15 studies to perform the meta-analysis. The meta-analysis indicated a heterogenicity of 84.7% with an odds ratio of 3.25 (2.66-3.96), indicating a significant risk of Alzheimer's disease, SARS-CoV-2, chemotherapy, and rhinosinusitis.
CONCLUSIONS
Inflammatory conditions and taste alterations are linked. Dysgeusia is associated with a higher risk of malnutrition and poorer general health status, especially in vulnerable populations.
Topics: Humans; Inflammation; Dysgeusia; Taste Perception; COVID-19; Alzheimer Disease; Taste; Malnutrition; SARS-CoV-2
PubMed: 38708467
DOI: 10.26355/eurrev_202404_36024 -
Cancers Apr 2023Complex anatomy surrounding the oropharynx makes proton therapy (PT), especially intensity-modulated PT (IMPT), a potentially attractive option due to its ability to... (Review)
Review
BACKGROUND
Complex anatomy surrounding the oropharynx makes proton therapy (PT), especially intensity-modulated PT (IMPT), a potentially attractive option due to its ability to reduce the volume of irradiated healthy tissues. Dosimetric improvement may not translate to clinically relevant benefits. As outcome data are emerging, we aimed to evaluate the evidence of the quality of life (QOL) and patient-reported outcomes (PROs) following PT for oropharyngeal carcinoma (OC).
MATERIALS AND METHODS
We searched PubMed and Scopus electronic databases (date: 15 February 2023) to identify original studies on QOL and PROs following PT for OC. We employed a fluid strategy in the search strategy by tracking citations of the initially selected studies. Reports were extracted for information on demographics, main results, and clinical and dose factor correlates. Quality assessment was performed using the NIH's Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. The PRISMA guidelines were followed in the preparation of this report.
RESULTS
Seven reports were selected, including one from a recently published paper captured from citation tracking. Five compared PT and photon-based therapy, although none were randomized controlled trials. Most endpoints with significant differences favored PT, including xerostomia, cough, need for nutritional supplements, dysgeusia, food taste, appetite, and general symptoms. However, some endpoints favored photon-based therapy (sexual symptoms) or showed no significant difference (e.g., fatigue, pain, sleep, mouth sores). The PROs and QOL improve following PT but do not appear to return to baseline.
CONCLUSION
Evidence suggests that PT causes less QOL and PRO deterioration than photon-based therapy. Biases due to the non-randomized study design remain obstacles to a firm conclusion. Whether or not PT is cost-effective should be the subject of further investigation.
PubMed: 37190180
DOI: 10.3390/cancers15082252 -
Systematic Review and Meta-analysis of Endoscopic vs Microscopic Stapes Surgery for Stapes Fixation.Otolaryngology--head and Neck Surgery :... Nov 2021To systematically review the current literature regarding the operative outcomes of stapes surgery for stapes fixation via the endoscopic and microscopic approaches. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To systematically review the current literature regarding the operative outcomes of stapes surgery for stapes fixation via the endoscopic and microscopic approaches.
DATA SOURCES
PubMed, Embase, and Web of Science.
REVIEW METHODS
An electronic search was conducted with the keywords "endoscop* or microscop*" and "stapes surgery or stapedectomy or stapedotomy or otosclerosis or stapes fixation." Studies were included if they compared endoscopy with microscopy for stapes surgery performed for stapes fixation and evaluated hearing outcomes and postoperative complications. Articles focusing on stapes surgery other than for stapes fixation were excluded.
RESULTS
The database search yielded 1317 studies; 12 remained after dual-investigator screening for quantitative analysis. The mean MINORS score was 18 of 24, indicating a low risk of bias. A meta-analysis demonstrated no statistically significant difference between the groups with regard to operative time, chorda tympani nerve manipulation or sacrifice, or postoperative vertigo. There was a 2.6-dB mean improvement in the change in air-bone gap in favor of endoscopic stapes surgery and a 15.2% increased incidence in postoperative dysgeusia in the microscopic group, but the studies are heterogeneous.
CONCLUSIONS
Endoscopic stapes surgery appears to be a reasonable alternative to microscopic stapes surgery, with similar operative times, complications, and hearing outcomes. Superior visibility with the endoscope was consistently reported in all the studies. Future studies should have standardized methods of reporting visibility, hearing outcomes, and postoperative complications to truly establish if endoscopic stapes surgery is equivalent or superior to microscopic stapes surgery.
Topics: Endoscopy; Humans; Microscopy; Microsurgery; Otosclerosis; Stapes Surgery
PubMed: 33528314
DOI: 10.1177/0194599821990669 -
The Laryngoscope Mar 2021Patients with chronic rhinosinusitis (CRS) often describe alterations in sense of taste. These complaints have historically been attributed to olfactory dysfunction;... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Patients with chronic rhinosinusitis (CRS) often describe alterations in sense of taste. These complaints have historically been attributed to olfactory dysfunction; however, there is evidence of direct, objective, gustatory disturbances in the setting of CRS that are not thoroughly characterized. This study sought to investigate and summarize gustatory dysfunction experienced by patients with CRS.
METHODS
PubMed, EMBASE, Cochrane Library, Web of Science, and Scopus databases were reviewed following PRISMA guidelines. English language, original studies investigating objective taste in adult patients with CRS were included. A meta-analysis with inverse variance, random-effects model was performed.
RESULTS
Of 2750 studies screened, 11 articles with 471 unique patients were included. Patients with CRS exhibit worse gustatory function compared to healthy controls (standardized mean difference 0.94 [95% CI, 0.44-1.45]). Hypogeusia was identified in 32/95 (33.7%) patients from three studies that used methods with a validated definition of hypogeusia. Older age, male gender, and smoking history were associated with taste dysfunction, while objective gustatory and olfactory dysfunction were not correlated. Subjective taste and quality of life measures were also not associated with objective taste. The impact of sinus surgery on objective taste is unclear.
CONCLUSION
Approximately 34% of patients with CRS experience hypogeusia. Neither olfactory function nor subjective taste were associated with objective gustatory function. Given the substantial prevalence of taste dysfunction patients with CRS, there is significant potential for growth in understanding of pathogenesis, impact on quality of life, and potential treatment strategies of taste impairment in the CRS patient population.
LEVEL OF EVIDENCE
1 Laryngoscope, 131:482-489, 2021.
Topics: Case-Control Studies; Chronic Disease; Female; Humans; Male; Middle Aged; Prevalence; Rhinitis; Sinusitis; Smell; Taste; Taste Disorders
PubMed: 32609889
DOI: 10.1002/lary.28827 -
Frontiers in Immunology 2020Systematic assessment of PD-1/PD-L1 inhibitor-related neurological toxicities is important for guiding anti-PD-1 and anti-PD-L1 immunotherapy. Therefore, we conducted... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Systematic assessment of PD-1/PD-L1 inhibitor-related neurological toxicities is important for guiding anti-PD-1 and anti-PD-L1 immunotherapy. Therefore, we conducted this meta-analysis to reveal the relationship between PD-1/PD-L1 inhibitors and neurological toxicities among cancer patients.
METHODS
Clinical trials investigating PD-1/PD-L1 inhibitors in cancer patients were identified by a systematic search of PubMed. The random-effect model was used to synthesize individual studies. Neurological toxicities, including all-grades and grades 3-5, were taken into account for the final comprehensive meta-analysis. The Newcastle Ottawa Scale (NOS) was used to assess the quality of included trials.
RESULTS
Thirty-one clinical trials containing data of neurological toxicities were included. Compared with chemotherapy, the risk of all-grade neurological toxicities caused by PD-1/PD-L1 inhibitors was much lower in terms of peripheral neuropathy [OR = 0.07, 95%CI:(0.04, 0.13)], peripheral sensory neuropathy [OR = 0.07, 95%CI(0.04, 0.12)], dysgeusia [OR = 0.26, 95%CI:(0.19, 0.35)], paraesthesia [OR = 0.23, 95%CI:(0.14, 0.36)], and polyneuropathy [OR = 0.12, 95%CI:(0.01, 0.94)]. However, for grades 3-5, the statistically significant results were only seen in peripheral neuropathy [OR = 0.15, 95%CI:(0.07, 0.34)] and peripheral sensory neuropathy [OR = 0.13, 95%CI:(0.04, 0.40)]. No statistically significant difference regarding the risk of headache, dizziness, and Guillain-Barré syndrome was found between PD-1/PD-L1 inhibitors and chemotherapy. For PD-1/PD-L1 inhibitors plus chemotherapy, the risk trends of the above-mentioned neurological toxicities, especially grades 3-5 peripheral neuropathy [OR = 1.76, 95%CI:(1.10, 2.82)] was increased compared to chemotherapy alone.
CONCLUSION
Our comprehensive analysis showed that PD-1/PD-L1 inhibitors alone exhibited lower neurological toxicities than chemotherapy. However, the risk of headache, dizziness, and Guillain-Barré syndrome was similar between PD-1/PD-L1 and chemotherapy. For PD-1/PD-L1 inhibitors plus chemotherapy, the incidence trend of neurological toxicities would be increased, especially for peripheral neuropathy of grades 3-5.
Topics: Antineoplastic Agents, Immunological; B7-H1 Antigen; Humans; Immune Checkpoint Inhibitors; Neoplasms; Nervous System Diseases; Programmed Cell Death 1 Receptor; Randomized Controlled Trials as Topic
PubMed: 33391266
DOI: 10.3389/fimmu.2020.595655 -
PloS One 2021Bisphosphonate drugs can be used to improve the outcomes of women with breast cancer. Whilst many meta-analyses have quantified their potential benefits for patients,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Bisphosphonate drugs can be used to improve the outcomes of women with breast cancer. Whilst many meta-analyses have quantified their potential benefits for patients, attempts at comprehensive quantification of potential adverse effects have been limited. We undertook a meta-analysis with novel methodology to identify and quantify these adverse effects.
METHODS
We systematically reviewed randomised controlled trials in breast cancer where at least one of the treatments was a bisphosphonate (zoledronic acid, ibandronate, pamidronate, alendronate or clodronate). Neoadjuvant, adjuvant and metastatic settings were examined. Primary outcomes were adverse events of any type or severity (excluding death). We carried out pairwise and network meta-analyses to estimate the size of any adverse effects potentially related to bisphosphonates. In order to ascertain whether adverse effects differed by individual factors such as age, or interacted with other common adjuvant breast cancer treatments, we examined individual-level patient data for one large trial, AZURE.
FINDINGS
We identified 56 trials that reported adverse data, which included a total of 29,248 patients (18,301 receiving bisphosphonate drugs versus 10,947 not). 24 out of the 103 different adverse outcomes analysed showed a statistically and practically significant increase in patients receiving a bisphosphonate drug compared with those not (2 additional outcomes that appeared statistically significant came only from small studies with low event counts and no clinical suspicion so are likely artifacts). Most of these 24 are already clinically recognised: 'flu-like symptoms, fever, headache and chills; increased bone pain, arthralgia, myalgia, back pain; cardiac events, thromboembolic events; hypocalcaemia and osteonecrosis of the jaw; as well as possibly stiffness and nausea. Oral clodronate appeared to increase the risk of vomiting and diarrhoea (which may also be increased by other bisphosphonates), and there may be some hepatotoxicity. Four additional potential adverse effects emerged for bisphosphonate drugs in this analysis which have not classically be recognised: fatigue, neurosensory problems, hypertonia/muscle spasms and possibly dysgeusia. Several symptoms previously reported as potential side effects in the literature were not significantly increased in this analysis: constipation, insomnia, respiratory problems, oedema or thirst/dry mouth. Individual patient-level data and subgroup analysis revealed little variation in side effects between women of different ages or menopausal status, those with metastatic versus non-metastatic cancer, or between women receiving different concurrent breast cancer therapies.
CONCLUSIONS
This meta-analysis has produced estimates for the absolute frequencies of a range of side effects significantly associated with bisphosphonate drugs when used by breast cancer patients. These results show good agreement with previous literature on the subject but are the first systematic quantification of side effects and their severities. However, the analysis is limited by the availability and quality of data on adverse events, and the potential for bias introduced by a lack of standards for reporting of such events. We therefore present a table of adverse effects for bisphosphonates, identified and quantified to the best of our ability from a large number of trials, which we hope can be used to improve the communication of the potential harms of these drugs to patients and their healthcare providers.
Topics: Adult; Aged; Aged, 80 and over; Bone Density Conservation Agents; Breast Neoplasms; Diphosphonates; Female; Humans; Middle Aged; Network Meta-Analysis; Randomized Controlled Trials as Topic; Young Adult
PubMed: 33544765
DOI: 10.1371/journal.pone.0246441 -
Clinical Therapeutics Mar 2023Pharmacologic cardioversion is an effective clinical strategy for fibrillation. Vernakalant is a novel drug used to treat atrial fibrillation (AF). This study aimed to... (Meta-Analysis)
Meta-Analysis
PURPOSE
Pharmacologic cardioversion is an effective clinical strategy for fibrillation. Vernakalant is a novel drug used to treat atrial fibrillation (AF). This study aimed to evaluate the efficacy- and tolerability-related data on vernakalant from clinical trials.
METHODS
Literature from PubMed and the Cochrane Library was systematically reviewed, and 139 eligible studies were found after specific key words were identified. Twelve randomized clinical trials discussing vernakalant cardioversion in patients with AF were chosen for the meta-analysis after scrutiny. Ten of the 12 trials used placebo while two reported data on active and established drugs to compare the effects of vernakalant. Three of the 12 trials included relevant clinical states in addition to AF.
FINDINGS
In this meta-analysis of data from 12 studies (2365 patients, 887 events), the rate of cardioversion from AF to sinus rhythm (SR) was significantly greater with vernakalant compared with placebo and active comparators (risk ratio = 5.60; 95% CI, 2.83-11.09; I test for heterogeneity, 92%). Tolerability-related data revealed that dysgeusia, paresthesia, atrial flutter, and hypotension were major adverse events that occurred with vernakalant use, but the data were not clinically significant compared to placebo and active drug (risk ratio = 1.13; 95% CI, 0.86-1.47). Eleven deaths were reported in 4 trials, with vernakalant directly implicated in two deaths. Vernakalant was well tolerated and effective in patients with rapid-onset AF.
IMPLICATIONS
Vernakalant appears to be a good choice when AF is manifested postoperatively or exists with ischemic heart disease and valvular states. Tolerability-related data are promising, but a specific trial may be required to identify the causes of the deaths considered unrelated to vernakalant use.
Topics: Humans; Atrial Fibrillation; Anti-Arrhythmia Agents; Electric Countershock; Treatment Outcome; Infusions, Intravenous; Pyrrolidines
PubMed: 36828756
DOI: 10.1016/j.clinthera.2023.01.014 -
Vestnik Otorinolaringologii 2023The presented systematic review contains basic information about the frequency, characteristic features of the course and pathogenesis of olfactory, gustatory and...
The presented systematic review contains basic information about the frequency, characteristic features of the course and pathogenesis of olfactory, gustatory and auditory disorders that occur with COVID-19, with which an otorhinolaryngologist meets in his practice. These disorders are often the first, and sometimes the only, manifestations of the underlying disease, which determines their role in early diagnosis and timely detection of the underlying disease. The article includes original articles, clinical case reports and literary reviews.
Topics: Humans; COVID-19; SARS-CoV-2; Olfaction Disorders; Smell; Early Diagnosis
PubMed: 38153895
DOI: 10.17116/otorino20238806161 -
Journal of the American Nutrition... 2023Hyponatremia is the most common electrolyte disturbance among hospitalized adults. Oral urea is currently recommended in Europe in the treatment of chronic hyponatremia;...
Hyponatremia is the most common electrolyte disturbance among hospitalized adults. Oral urea is currently recommended in Europe in the treatment of chronic hyponatremia; no published systematic review investigating oral urea for acute hyponatremia among hospitalized adults exists. An oral urea supplement became available in the United States in 2016. This was a systematic review investigating the use of oral urea in the treatment of acute hyponatremia among hospitalized adults. Pubmed, CINAHL, Scopus, Web of Science, and Cochrane databases were searched for studies published between 1998 and 2021. Risk of bias was assessed using the ROBINS-I tool; strength of the evidence was assessed using GRADE criteria. Changes in serum sodium and measures of safety and tolerance were reported. Eight studies were identified that met inclusion criteria, which included a total of 296 patients. Seven studies were retrospective. All studies found an increase in serum sodium levels associated with oral urea supplementation. Side effects were minimal; one patient discontinued urea due to a side effect (dysgeusia). Urea dose/duration varied among the studies. Based on the serious risk of bias and GRADE criteria, the strength of the evidence was considered low. Oral urea supplementation was associated with increases in serum sodium concentrations among hospitalized adults with hyponatremia, and appears to be safe and well tolerated in this population. Prospective controlled trials are needed to establish the efficacy, comparative effectiveness, and potential cost savings of this therapy.Key teaching pointsHyponatremia is associated with negative clinical outcomes among hospitalized adults.Oral urea is now available in the United States, and is currently recommended in Europe to treat chronic hyponatremia.This systematic review shows that oral urea supplementation may be associated with increases in serum sodium levels among hospitalized adults with hyponatremia, and appears safe and well-tolerated; however, the studies reviewed here are at high risk of bias and the available evidence is of low quality, making any recommendation drawn from this data weak.Prospective controlled trials are needed to establish the efficacy, comparative effectiveness, and potential cost savings of oral urea supplementation for hyponatremia.
Topics: Humans; Adult; Hyponatremia; Urea; Retrospective Studies; Prospective Studies; Sodium; Dietary Supplements
PubMed: 35512769
DOI: 10.1080/07315724.2022.2036267