-
JAMA Network Open Apr 2022Neurologic adverse events (NAEs) due to immune checkpoint inhibitors (ICIs) can be fatal but are underexplored. (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Neurologic adverse events (NAEs) due to immune checkpoint inhibitors (ICIs) can be fatal but are underexplored.
OBJECTIVE
To compare NAEs reported in randomized clinical trials (RCTs) of US Food and Drug Administration-approved ICIs with other forms of chemotherapy and placebo.
DATA SOURCES
Bibliographic databases (Embase, Ovid, MEDLINE, and Scopus data) and trial registries (ClinicalTrials.gov) were searched from inception through March 1, 2020.
STUDY SELECTION
Phase II/III RCTs evaluating the use of ICIs were eligible for inclusion. Unpublished trials were excluded from the analysis.
DATA EXTRACTION AND SYNTHESIS
Two investigators independently performed screening of trials using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline. NAEs were recorded for each arm. Data were pooled using a random-effects model.
MAIN OUTCOMES AND MEASURES
The risk of NAEs with ICI use compared with any drug regimen, cytotoxic chemotherapy, and placebo.
RESULTS
A total 39 trials including 23 705 patients were analyzed (16 135 [68.0%] men, 7866 [33.1%] White). The overall risk of a NAE was lower in the ICI group (risk ratio [RR], 0.59; 95% CI, 0.45-0.77) and in the subgroup of RCTs comparing ICI use with chemotherapy (RR, 0.22; 95% CI, 0.13-0.39). In the subgroup of RCTs comparing ICI with placebo, the overall risk of NAE was significantly higher in the ICI group (RR, 1.57; 95% CI, 1.30-1.89). Peripheral neuropathy (RR, 0.30; 95% CI, 0.17-0.51) and dysgeusia (RR, 0.41; 95% CI, 0.27-0.63) were significantly lower in the ICI group. Headache was more common with the use of ICIs (RR, 1.32; 95% CI, 1.10-1.59). In the subgroup analysis of RCTs comparing ICI use with chemotherapy, peripheral neuropathy (RR, 0.09; 95% CI, 0.05-0.17), dysgeusia (RR, 0.42; 95% CI, 0.21-0.85), and paresthesia (RR, 0.29; 95% CI, 0.13-0.67) were significantly lower in the ICI group. RCTs comparing ICIs with placebo showed a higher risk of headache with ICI use (RR, 1.63; 95%, CI, 1.32-2.02).
CONCLUSIONS AND RELEVANCE
Results of this meta-analysis suggest that the overall risk of NAEs, peripheral neuropathy, and dysgeusia is lower with the use of ICI. When compared with chemotherapy, the overall risk of NAE, peripheral neuropathy, paresthesia, and dysgeusia was lower with ICI use; however, when compared with placebo, the risk of NAEs is higher with the use of ICI.
Topics: Dysgeusia; Female; Headache; Humans; Immune Checkpoint Inhibitors; Male; Paresthesia; United States
PubMed: 35438755
DOI: 10.1001/jamanetworkopen.2022.7722 -
Reviews in the Neurosciences Apr 2021The ongoing pandemic of Coronavirus disease 2019 (COVID-19) has infected more than 27 million confirmed cases and 8,90,000 deaths all around the world. Verity of viral... (Meta-Analysis)
Meta-Analysis
The ongoing pandemic of Coronavirus disease 2019 (COVID-19) has infected more than 27 million confirmed cases and 8,90,000 deaths all around the world. Verity of viral infections can infect the nervous system; these viral infections can present a wide range of manifestation. The aim of the current study was to systematically review the COVID-19 associated central nervous system manifestations, mental and neurological symptoms. For that we conducted a comprehensive systematic literature review of four online databases, including Web of Science, PubMed, Scopus and Embase. All relevant articles that reported psychiatric/psychological symptoms or disorders in COVID-19 without considering time and language restrictions were assessed. All the study procedures were performed based on the PRISMA criteria. Due to the screening, 14 studies were included. The current study result indicated that, the pooled prevalence of CNS or mental associated disorders with 95% CI was 50.68% (6.68-93.88). The most prevalence symptoms were hyposmia/anosmia/olfactory dysfunction (number of study: 10) with 36.20% (14.99-60.51). Only one study reported numbness/paresthesia and dysphonia. Pooled prevalence of numbness/paresthesia and dysphonia was 5.83% (2.17-12.25) and 2.39% (10.75-14.22). The pooled prevalence of depression and anxiety was 3.52% (2.62-4.54) and 13.92% (9.44-19.08). Our findings demonstrate that COVID-19 has a certain relation with neurological symptoms. The hypsomia, anosmia or olfactory dysfunction was most frequent symptom. Other symptoms were headache or dizziness, dysgeusia or ageusia, dysphonia and fatigue. Depression, anxiety, and confusion were less frequent symptoms.
Topics: Anosmia; Anxiety; COVID-19; Depression; Dysgeusia; Dysphonia; Fatigue; Headache; Humans; Hypesthesia; Nervous System Diseases; Paresthesia; Prevalence; SARS-CoV-2
PubMed: 33618441
DOI: 10.1515/revneuro-2020-0108 -
Frontiers in Oncology 2022This review aimed to comprehensively analyze the safety and efficacy of erdafitinib in treating advanced and metastatic urothelial carcinoma and other solid tumors.
OBJECTIVE
This review aimed to comprehensively analyze the safety and efficacy of erdafitinib in treating advanced and metastatic urothelial carcinoma and other solid tumors.
METHODS
PubMed, Embase, and ClinicalTrials.gov were searched until 10 February 2022. The safety outcome as adverse events and efficacy outcomes, including objective response rate, stable disease rates, and progressive disease rates, were selected and analyzed by comprehensive meta-analysis version 3.0 and STATA 15.0.
RESULTS
The most common all-grade adverse events were hyperphosphatemia, dry mouth, stomatitis, diarrhea, and dysgeusia. The occurrence of ≥3 adverse events was relatively low, and stomatitis and hyponatremia were the most common. Moreover, eye disorders could not be ignored. Efficacy in urothelial carcinoma patients was obviously better than in other solid tumor patients, with a higher objective response rate (0.38 versus 0.10) and lower progressive disease rate (0.26 versus 0.68). All responses occurred in patients with fibroblast growth factor receptor (FGFR) alteration. In those patients, a specific FGFR alteration () was observed to have a maximum response.
CONCLUSION
Erdafitinib has satisfactory clinical activity for metastatic urothelial carcinoma and other solid tumors, while the toxicity is acceptable. With more RCTs and combination therapy trials published, erdafitinib will be applied widely.
PubMed: 36776367
DOI: 10.3389/fonc.2022.907377 -
International Journal of Environmental... Oct 2022Individuals with chronic kidney disease (CKD) experience physiological changes that likely impair salt taste function and perception. Sodium restriction is a cornerstone... (Review)
Review
Individuals with chronic kidney disease (CKD) experience physiological changes that likely impair salt taste function and perception. Sodium restriction is a cornerstone of CKD management but dietary sodium plays an important role in food enjoyment and may interfere with compliance to this intervention. Therefore, confirming that taste deficits are present in CKD will improve our understanding of how taste deficits can affect intake, and inform dietary counselling in the future. A systematic review was conducted. Studies that included adults with CKD and healthy controls, and assessed salt taste sensitivity, perceived intensity, and/or hedonic ratings were included. Study quality was assessed using the Academy of Nutrition and Dietetics Evidence Analysis Library Quality Criteria Checklist: Primary Research. Of the 16 studies, the majority reported decreased salt taste sensitivity, but no consistent differences in intensity or hedonic ratings were observed. Higher recognition thresholds in CKD patients were associated with higher sodium intake, but results should be interpreted with caution as the measures used were subject to error in this population. In conclusion, salt taste sensitivity is decreased in CKD, but intensity and hedonic evaluations appear to be more robust. Given that hedonic assessments are better predictors of intake, and that salt taste preferences can be changed over time, dietary counselling for low-sodium intake is likely to be effective for this population.
Topics: Adult; Dysgeusia; Food Preferences; Humans; Perception; Renal Insufficiency, Chronic; Sodium; Sodium, Dietary; Taste
PubMed: 36231932
DOI: 10.3390/ijerph191912632 -
Epilepsia Dec 2015Topiramate (TPM) is an antiepileptic drug that is also used for other indications (e.g., migraine). Adverse event (AE) data from epilepsy trials could be supplemented by... (Review)
Review
OBJECTIVE
Topiramate (TPM) is an antiepileptic drug that is also used for other indications (e.g., migraine). Adverse event (AE) data from epilepsy trials could be supplemented by data from trials in other indications. Combining data across trials and indications is a novel method for evaluating AEs. We conducted a multiple-indications review by systematically reviewing randomized placebo-controlled trials of TPM, to compare the nervous system AEs of TPM in epilepsy with those in other indications.
METHODS
Randomized placebo-controlled trials of TPM including patients with any indication were included. We searched Cochrane Central Register of Controlled Trials (Issue 2, 2012) and MEDLINE (1966-February 2012). Two authors assessed eligibility and risk of bias, and extracted data. For each reported nervous system AE, we extracted event rates, applied random-effects inverse-variance meta-analysis (pooling within-indications then across-indications), and assessed within- and across-indication heterogeneity.
RESULTS
Ninety trials, including 16 epilepsy trials, were included. A difference was detected between TPM and placebo for three events (i.e., drooling, dysgeusia, and hypoesthesia) that were not reported in epilepsy trials but were reported by other trials. A difference between TPM and placebo was detected for speech disorder using epilepsy trials but not when combining all trials. For two events (i.e., cognitive disorder and "language problems"), no difference was detected between TPM and placebo when using epilepsy trials alone, but a difference was identified using all trials. A difference was detected between TPM and placebo for six events (i.e., ataxia, disturbance in attention, dizziness, memory impairment, paraesthesia, and somnolence) when using epilepsy trials alone, and using all trials.
SIGNIFICANCE
Including trials of any indication enabled detection of differences that would have been missed using epilepsy trials alone. Multiple-indications reviews can improve the synthesis of AEs for antiepileptic drugs.
Topics: Anticonvulsants; Epilepsy; Fructose; Humans; Randomized Controlled Trials as Topic; Topiramate
PubMed: 26662191
DOI: 10.1111/epi.13209 -
The Egyptian Journal of Neurology,... 2021COVID-19 infection can show various manifestation, including neurologic manifestations, such as , , or , and causes the neurologic disorder such as stroke,... (Review)
Review
BACKGROUND
COVID-19 infection can show various manifestation, including neurologic manifestations, such as , , or , and causes the neurologic disorder such as stroke, Guillain-Barre syndrome, encephalopathy, and many more.
AIM
To briefly review neurologic manifestation in COVID-19 infection in the Asia region (South East Asia and the Western Pacific Region).
MATERIAL AND METHODS
This review uses the PRISMA statement and checklist. The source for reviewed article was performed in PubMed that were published between December 2019 to September 2020 with the latest 1 year of publication. Study titles were first screened, then reviewed by title and abstract and then the last review, we tested full text and applied eligibility criteria.
RESULTS
We found a total of 9 retrieved articles from the electronic database. Among these 9 articles, 5 of them are case report, 1 case series, 1 prospective multi-center cohort study, 1 retrospective multi-center study, and 1 retrospective observational study. All articles reported confirmed COVID-19, confirmation by positive swab test using the real-time RT-PCR method, with neurologic manifestations, disorder, or syndrome on presentation or found during hospital stay. In case of neurologic disorder or syndrome, the studies reported encephalitis and ADEM, acute cerebrovascular disease, acute symptomatic seizure, and Guillain-Barré syndrome with acute cerebrovascular disease as the most common neurologic disorder associated with COVID-19 infection, followed by encephalitis.
CONCLUSION
COVID-19 also affects the brain, which may result in a global or focal neurologic manifestation. Healthcare provider treating patient with COVID-19 infection should also be aware of neurologic manifestation associated with COVID-19 infection to improve patient's outcome.Guillain-Barre syndrome, encephalopathy, and many more. This review will briefly review neurologic manifestation in COVID-19 infection in the Asian region (South East Asia and the Western Pacific Region. A total of 9 retrieved articles from the electronic database reported confirmed COVID-19, confirmation by RT-PCR method, with neurologic manifestation, disorder, or syndrome on presentation or found during hospital stay. Healthcare provider treating patient with COVID-19 infection should also be aware of neurologic manifestation associated with COVID-19 infection to improve patient's outcome.
PubMed: 33613024
DOI: 10.1186/s41983-021-00279-3 -
Mayo Clinic Proceedings Aug 2020To estimate the prevalence of olfactory and gustatory dysfunctions (OGDs) among patients infected with novel coronavirus disease 2019 (COVID-19). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To estimate the prevalence of olfactory and gustatory dysfunctions (OGDs) among patients infected with novel coronavirus disease 2019 (COVID-19).
METHODS
A systematic review was conducted by searching MEDLINE, EMBASE, and the preprint server MedRxiv from their inception until May 11, 2020, using the terms anosmia or hyposmia or dysosmia or olfactory dysfunction or olfaction disorder or smell dysfunction or ageusia or hypogeusia or dysgeusia or taste dysfunction or gustatory dysfunction or neurological and COVID-19 or 2019 novel coronavirus or 2019-nCoV or SARS-CoV-2. The references of included studies were also manually screened. Only studies involving patients with diagnostic-confirmed COVID-19 infection were included. Random-effects meta-analysis was performed.
RESULTS
Twenty-four studies with data from 8438 patients with test-confirmed COVID-19 infection from 13 countries were included. The pooled proportions of patients presenting with olfactory dysfunction and gustatory dysfunction were 41.0% (95% CI, 28.5% to 53.9%) and 38.2% (95% CI, 24.0% to 53.6%), respectively. Increasing mean age correlated with lower prevalence of olfactory (coefficient = -0.076; P=.02) and gustatory (coefficient = -0.073; P=.03) dysfunctions. There was a higher prevalence of olfactory dysfunctions with the use of objective measurements compared with self-reports (coefficient = 2.33; P=.01). No significant moderation of the prevalence of OGDs by sex was observed.
CONCLUSION
There is a high prevalence of OGDs among patients infected with COVID-19. Routine screening for these conditions could contribute to improved case detection in the ongoing COVID-19 pandemic. However, to better inform population screening measures, further studies are needed to establish causality.
Topics: Betacoronavirus; COVID-19; COVID-19 Testing; Clinical Laboratory Techniques; Coronavirus Infections; Global Health; Humans; Olfaction Disorders; Pandemics; Pneumonia, Viral; Prevalence; SARS-CoV-2; Taste Disorders
PubMed: 32753137
DOI: 10.1016/j.mayocp.2020.05.030 -
Clinical and Experimental... Aug 2021This study evaluated the diagnostic value of various symptoms of coronavirus disease 2019 (COVID-19) in screening for this disease.
OBJECTIVES
This study evaluated the diagnostic value of various symptoms of coronavirus disease 2019 (COVID-19) in screening for this disease.
METHODS
Two authors (working independently) comprehensively reviewed six databases (PubMed, Cochrane Database, Embase, Web of Science, Scopus, and Google Scholar) from their dates of inception until November 2020. The predictive value of patient-reported symptoms, including otolaryngologic and general symptoms, was evaluated in adults who underwent testing for COVID-19. True-positive, true-negative, false-positive, and false-negative data were extracted from each study. The methodological quality of the included studies was evaluated using the quality assessment of diagnostic accuracy studies tool (ver. 2).
RESULTS
Twenty-eight prospective and retrospective studies were included in the meta-analysis. The diagnostic odds ratio (DOR) of a change in olfaction and/or taste was 10.20 (95% confidence interval [CI], 8.43-12.34). The area under the summary receiver operating characteristic curve was 0.8. Olfactory and/or taste changes had a low sensitivity (0.57; 95% CI, 0.47-0.66) but moderate negative (0.78; 95% CI, 0.69-0.85] and positive (0.78; 95% CI, 0.66-0.87) predictive values and a high specificity (0.91; 95% CI, 0.83-0.96). Olfactory and/or taste changes had a higher diagnostic value than the other otolaryngologic symptoms, a higher DOR and specificity, and a similar or higher diagnostic value than the other general symptoms.
CONCLUSION
Among otolaryngologic symptoms, olfactory and/or taste dysfunction was the most closely associated with COVID-19 and its general symptoms, and should therefore be considered when screening for the disease.
PubMed: 33541033
DOI: 10.21053/ceo.2020.02369 -
Reviews in Medical Virology Sep 2021In a large-scale study, 128176 non-pregnant patients (228 studies) and 10000 pregnant patients (121 studies) confirmed COVID-19 cases included in this Meta-Analysis. The... (Meta-Analysis)
Meta-Analysis
In a large-scale study, 128176 non-pregnant patients (228 studies) and 10000 pregnant patients (121 studies) confirmed COVID-19 cases included in this Meta-Analysis. The mean (confidence interval [CI]) of age and gestational age of admission (GA) in pregnant women was 33 (28-37) years old and 36 (34-37) weeks, respectively. Pregnant women show the same manifestations of COVID-19 as non-pregnant adult patients. Fever (pregnant: 75.5%; non-pregnant: 74%) and cough (pregnant: 48.5%; non-pregnant: 53.5%) are the most common symptoms in both groups followed by myalgia (26.5%) and chill (25%) in pregnant and dysgeusia (27%) and fatigue (26.5%) in non-pregnant patients. Pregnant women are less probable to show cough (odds ratio [OR] 0.7; 95% CI 0.67-0.75), fatigue (OR: 0.58; CI: 0.54-0.61), sore throat (OR: 0.66; CI: 0.61-0.7), headache (OR: 0.55; CI: 0.55-0.58) and diarrhea (OR: 0.46; CI: 0.4-0.51) than non-pregnant adult patients. The most common imaging found in pregnant women is ground-glass opacity (57%) and in non-pregnant patients is consolidation (76%). Pregnant women have higher proportion of leukocytosis (27% vs. 14%), thrombocytopenia (18% vs. 12.5%) and have lower proportion of raised C-reactive protein (52% vs. 81%) compared with non-pregnant patients. Leucopenia and lymphopenia are almost the same in both groups. The most common comorbidity in pregnant patients is diabetes (18%) and in non-pregnant patients is hypertension (21%). Case fatality rate (CFR) of non-pregnant hospitalized patients is 6.4% (4.4-8.5), and mortality due to all-cause for pregnant patients is 11.3% (9.6-13.3). Regarding the complications of pregnancy, postpartum hemorrhage (54.5% [7-94]), caesarean delivery (48% [42-54]), preterm labor (25% [4-74]) and preterm birth (21% [12-34]) are in turn the most prevalent complications. Comparing the pregnancy outcomes show that caesarean delivery (OR: 3; CI: 2-5), low birth weight (LBW) (OR: 9; CI: 2.4-30) and preterm birth (OR: 2.5; CI: 1.5-3.5) are more probable in pregnant woman with COVID-19 than pregnant women without COVID-19. The most prevalent neonatal complications are neonatal intensive care unit admission (43% [2-96]), fetal distress (30% [12-58]) and LBW (25% [16-37]). The rate of vertical transmission is 5.3% (1.3-16), and the rate of positive SARS-CoV-2 test for neonates born to mothers with COVID-19 is 8% (4-16). Overall, pregnant patients present with the similar clinical characteristics of COVID-19 when compared with the general population, but they may be more asymptomatic. Higher odds of caesarean delivery, LBW and preterm birth among pregnant patients with COVID-19 suggest a possible association between COVID-19 infection and pregnancy complications. Low risk of vertical transmission is present, and SARS-CoV-2 can be detected in all conception products, particularly placenta and breast milk. Interpretations of these results should be done cautiously due to the heterogeneity between studies; however, we believe our findings can guide the prenatal and postnatal considerations for COVID-19 pregnant patients.
Topics: Adult; COVID-19; Female; Humans; Infant, Newborn; Infant, Newborn, Diseases; Infectious Disease Transmission, Vertical; Male; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome; Pregnant Women; Premature Birth; SARS-CoV-2
PubMed: 33387448
DOI: 10.1002/rmv.2208 -
The Cochrane Database of Systematic... Oct 2014Lower respiratory tract infection (LRTI) is the third leading cause of death worldwide and the first leading cause of death in low-income countries. Community-acquired... (Review)
Review
BACKGROUND
Lower respiratory tract infection (LRTI) is the third leading cause of death worldwide and the first leading cause of death in low-income countries. Community-acquired pneumonia (CAP) is a common condition that causes a significant disease burden for the community, particularly in children younger than five years, the elderly and immunocompromised people. Antibiotics are the standard treatment for CAP. However, increasing antibiotic use is associated with the development of bacterial resistance and side effects for the patient. Several studies have been published regarding optimal antibiotic treatment for CAP but many of these data address treatments in hospitalised patients. This is an update of our 2009 Cochrane Review and addresses antibiotic therapies for CAP in outpatient settings.
OBJECTIVES
To compare the efficacy and safety of different antibiotic treatments for CAP in participants older than 12 years treated in outpatient settings with respect to clinical, radiological and bacteriological outcomes.
SEARCH METHODS
We searched CENTRAL (2014, Issue 1), MEDLINE (January 1966 to March week 3, 2014), EMBASE (January 1974 to March 2014), CINAHL (2009 to March 2014), Web of Science (2009 to March 2014) and LILACS (2009 to March 2014).
SELECTION CRITERIA
We looked for randomised controlled trials (RCTs), fully published in peer-reviewed journals, of antibiotics versus placebo as well as antibiotics versus another antibiotic for the treatment of CAP in outpatient settings in participants older than 12 years of age. However, we did not find any studies of antibiotics versus placebo. Therefore, this review includes RCTs of one or more antibiotics, which report the diagnostic criteria and describe the clinical outcomes considered for inclusion in this review.
DATA COLLECTION AND ANALYSIS
Two review authors (LMB, TJMV) independently assessed study reports in the first publication. In the 2009 update, LMB performed study selection, which was checked by TJMV and MMK. In this 2014 update, two review authors (SP, SM) independently performed and checked study selection. We contacted trial authors to resolve any ambiguities in the study reports. We compiled and analysed the data. We resolved differences between review authors by discussion and consensus.
MAIN RESULTS
We included 11 RCTs in this review update (3352 participants older than 12 years with a diagnosis of CAP); 10 RCTs assessed nine antibiotic pairs (3321 participants) and one RCT assessed four antibiotics (31 participants) in people with CAP. The study quality was generally good, with some differences in the extent of the reporting. A variety of clinical, bacteriological and adverse events were reported. Overall, there was no significant difference in the efficacy of the various antibiotics. Studies evaluating clarithromycin and amoxicillin provided only descriptive data regarding the primary outcome. Though the majority of adverse events were similar between all antibiotics, nemonoxacin demonstrated higher gastrointestinal and nervous system adverse events when compared to levofloxacin, while cethromycin demonstrated significantly more nervous system side effects, especially dysgeusia, when compared to clarithromycin. Similarly, high-dose amoxicillin (1 g three times a day) was associated with higher incidence of gastritis and diarrhoea compared to clarithromycin, azithromycin and levofloxacin.
AUTHORS' CONCLUSIONS
Available evidence from recent RCTs is insufficient to make new evidence-based recommendations for the choice of antibiotic to be used for the treatment of CAP in outpatient settings. Pooling of study data was limited by the very low number of studies assessing the same antibiotic pairs. Individual study results do not reveal significant differences in efficacy between various antibiotics and antibiotic groups. However, two studies did find significantly more adverse events with use of cethromycin as compared to clarithromycin and nemonoxacin when compared to levofloxacin. Multi-drug comparisons using similar administration schedules are needed to provide the evidence necessary for practice recommendations. Further studies focusing on diagnosis, management, cost-effectiveness and misuse of antibiotics in CAP and LRTI are warranted in high-, middle- and low-income countries.
Topics: Adult; Anti-Bacterial Agents; Community-Acquired Infections; Humans; Outpatients; Pneumonia; Randomized Controlled Trials as Topic
PubMed: 25300166
DOI: 10.1002/14651858.CD002109.pub4