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The Laryngoscope Mar 2024With widespread vaccination against COVID-19, concerns regarding side effects have been raised. We aim to assess the frequency of otolaryngologic adverse events (AEs)...
OBJECTIVES
With widespread vaccination against COVID-19, concerns regarding side effects have been raised. We aim to assess the frequency of otolaryngologic adverse events (AEs) following COVID-19 vaccination as compared with other vaccines in a national database.
STUDY DESIGN
Retrospective analysis of national registry.
METHODS
The Food and Drug Administration's Vaccine Adverse Event Reporting System (VAERS) database was queried from December 2020 to May 2021 for all COVID-19 vaccination AEs. Complaints were categorized as otolaryngologic and sub stratified into different anatomic components. Reporting odds ratios (ROR) and proportional reporting ratios (PRR) were determined for AEs of clinical significance.
RESULTS
The total number of AEs reported from vaccination with the Moderna, Pfizer-BioNTech, and Janssen vaccines equaled 1,280,950. Of these, 62,660 (4.9%) were otolaryngologic in nature, with 32.6% associated with the oropharynx/larynx, 18.3% with the nasal cavity/sinuses, 17.1% with the ears/vestibular system, 10.0% with the oral cavity, and 21.9% miscellaneous. Signal ratios reached significance levels for dysgeusia (n = 2124, PRR: 17.33, ROR: 16.36), ageusia (n = 1376, PRR: 2.81, ROR: 2.81), anosmia (n = 983, PRR: 4.01, ROR: 4.01), rhinorrhea (n = 2203, PRR: 2.99, ROR: 3.00), throat tightness (n = 3666, PRR: 4.99, ROR: 5.00), throat irritation (n = 3313, PRR: 4.51, ROR: 4.52), dysphagia (n = 2538, PRR: 2.07, ROR: 2.07), tinnitus (n = 4377, PRR: 3.97, ROR: 3.98), and vertigo (n = 2887, PRR: 3.93, ROR: 3.93). Signal ratios were not significant for facial paralysis, Bell's palsy, anaphylaxis, sinusitis, hearing disability, and ear pain.
CONCLUSIONS
Although several otolaryngologic symptoms were reported, few were found to be clinically significant. Of note, facial paralysis, Bell's palsy, and anaphylaxis did not meet signal thresholds to be determined significant.
LEVEL OF EVIDENCE
4 Laryngoscope, 134:1163-1168, 2024.
Topics: Humans; COVID-19 Vaccines; Anaphylaxis; Bell Palsy; Facial Paralysis; Pharynx; Retrospective Studies; Adverse Drug Reaction Reporting Systems; COVID-19; Vaccines; Vaccination
PubMed: 37539984
DOI: 10.1002/lary.30923 -
Cancers Apr 2024Despite a better understanding of the mechanisms causing cancer cachexia (CC) and development of promising pharmacologic and supportive care interventions, CC persists... (Review)
Review
Despite a better understanding of the mechanisms causing cancer cachexia (CC) and development of promising pharmacologic and supportive care interventions, CC persists as an underdiagnosed and undertreated condition. CC contributes to fatigue, poor quality of life, functional impairment, increases treatment related toxicity, and reduces survival. The core elements of CC such as weight loss and poor appetite should be identified early. Currently, addressing contributing conditions (hypothyroidism, hypogonadism, and adrenal insufficiency), managing nutrition impact symptoms leading to decreased oral intake (nausea, constipation, dysgeusia, stomatitis, mucositis, pain, fatigue, depressed mood, or anxiety), and the addition of pharmacologic agents when appropriate (progesterone analog, corticosteroids, and olanzapine) is recommended. In Japan, the clinical practice has changed based on the availability of Anamorelin, a ghrelin receptor agonist that improved lean body mass, weight, and appetite-related quality of life (QoL) compared to a placebo, in phase III trials. Other promising therapeutic agents currently in trials include Espindolol, a non-selective β blocker and a monoclonal antibody to GDF-15. In the future, a single therapeutic agent or perhaps multiple medications targeting the various mechanisms of CC may prove to be an effective strategy. Ideally, these medications should be incorporated into a multimodal interdisciplinary approach that includes exercise and nutrition.
PubMed: 38730648
DOI: 10.3390/cancers16091696 -
Otolaryngology--head and Neck Surgery :... Jul 2023A novel COVID-19 therapeutic, nirmatrelvir/ritonavir (Paxlovid), is commonly associated with reports of dysgeusia. The Food and Drug Administration Adverse Event... (Observational Study)
Observational Study
OBJECTIVE
A novel COVID-19 therapeutic, nirmatrelvir/ritonavir (Paxlovid), is commonly associated with reports of dysgeusia. The Food and Drug Administration Adverse Event Reporting System (FAERS) database was used to determine the real-world reporting of Paxlovid-associated dysgeusia (PAD), identify associated factors, and describe the relative reporting rates of dysgeusia for Paxlovid compared to other COVID-19 therapeutics (OCT), ritonavir alone, and other protease inhibitors (OPI).
STUDY DESIGN
Observational retrospective.
SETTING
Tertiary academic medical center.
METHODS
We collected patient and adverse event characteristics reported in the FAERS database between January 1968 and September 2022. Disproportionality analyses were used to compare the reporting of PAD to dysgeusia reported for OCT, ritonavir, and OPI.
RESULTS
345,229 adverse events were included in the present study. Dysgeusia was a frequently reported Paxlovid-associated adverse event (17.5%) and was associated with nonserious COVID-19 infection (reporting odds ratio [ROR] 1.4; 95% confidence interval [CI] 1.2, 1.7) and female sex (ROR = 1.7; 95% CI 1.6, 1.9). Paxlovid was more likely to be associated with the reporting of dysgeusia compared to OCT (ROR 305.4; 95% CI 164.1, 568.5), ritonavir (ROR 28.0; 95% CI 24.1, 32.7), and OPI (ROR 49.0; 95% CI 42.8, 56.1).
CONCLUSION
Dysgeusia is much more likely to be reported by patients receiving Paxlovid than those receiving OCT, ritonavir alone, or OPI. These findings suggest a potential mechanism of dysgeusia that causes distorted taste out of proportion to the background effects of COVID-19 infection and specific to nirmatrelvir. Future studies are needed to determine the underlying pathophysiology and long-term clinical implications for patients who report dysgeusia with Paxlovid.
Topics: Female; Humans; COVID-19; Dysgeusia; Pharmacovigilance; Retrospective Studies; Ritonavir; United States
PubMed: 36821807
DOI: 10.1002/ohn.278 -
Analytical Cellular Pathology... 2023Angiotensin-converting enzyme 2 (ACE2), a key enzyme in the renin-angiotensin system (RAS), is expressed in various tissues and organs, including the central nervous... (Review)
Review
Angiotensin-converting enzyme 2 (ACE2), a key enzyme in the renin-angiotensin system (RAS), is expressed in various tissues and organs, including the central nervous system (CNS). The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease-2019 (COVID-19), binds to ACE2, which raises concerns about the potential for viral infection in the CNS. There are numerous reports suggesting a link between SARS-CoV-2 infection and neurological manifestations. This study aimed to present an updated review of the role of brain RAS components, especially ACE2, in neurological complications induced by SARS-CoV-2 infection. Several routes of SARS-CoV-2 entry into the brain have been proposed. Because an anosmia condition appeared broadly in COVID-19 patients, the olfactory nerve route was suggested as an early pathway for SARS-CoV-2 entry into the brain. In addition, a hematogenous route via disintegrations in the blood-brain barrier following an increase in systemic cytokine and chemokine levels and retrograde axonal transport, especially via the vagus nerve innervating lungs, have been described. Common nonspecific neurological symptoms in COVID-19 patients are myalgia, headache, anosmia, and dysgeusia. However, more severe outcomes include cerebrovascular diseases, cognitive impairment, anxiety, encephalopathy, and stroke. Alterations in brain RAS components such as angiotensin II (Ang II) and ACE2 mediate neurological manifestations of SARS-CoV-2 infection, at least in part. Downregulation of ACE2 due to SARS-CoV-2 infection, followed by an increase in Ang II levels, leads to hyperinflammation and oxidative stress, which in turn accelerates neurodegeneration in the brain. Furthermore, ACE2 downregulation in the hypothalamus induces stress and anxiety responses by increasing corticotropin-releasing hormone. SARS-CoV-2 infection may also dysregulate the CNS neurotransmission, leading to neurological complications observed in severe cases of COVID-19. It can be concluded that the neurological manifestations of COVID-19 may be partially associated with changes in brain RAS components.
Topics: Humans; SARS-CoV-2; COVID-19; Renin-Angiotensin System; Angiotensin-Converting Enzyme 2; Peptidyl-Dipeptidase A; Anosmia; Brain
PubMed: 37575318
DOI: 10.1155/2023/8883492 -
Journal of Oral Pathology & Medicine :... Aug 2023Oral and/or oropharyngeal cancers account for approximately 2% of all malignancies, with variation across age groups, genders, and geographic locations. Treatments for... (Review)
Review
BACKGROUND
Oral and/or oropharyngeal cancers account for approximately 2% of all malignancies, with variation across age groups, genders, and geographic locations. Treatments for oral and/or oropharyngeal cancers usually consist of a combination of surgical excision most commonly followed by radiotherapy ± chemotherapy and/or immunotherapy/biotherapy depending on the nature of the malignancy. The significant morbidity caused by high-dose radiotherapy to the head and neck region is widely observed. Proton therapy is a promising treatment option that localises a proton beam to direct radiation at a specific target, with reduced irradiation to adjacent structures.
METHOD
The objective was to explore the toxicity associated with proton therapy for adults with oral and/or oropharyngeal cancer. Eligibility criteria included full-text articles, English articles, published between up till 7 January 2023. Databases included PubMed, Scopus, Web of Science, Embase, and Scopus.
RESULTS
The systematic search identified 345 studies and a total of 18 studies were included after two independent reviewers completed title, abstract, and full-text screening. Included studies were from four countries, and median participant age range was 53.3 to 66 years. The most commonly reported acute toxic effects included dysphagia, radiation dermatitis, oral mucositis, dysgeusia, and alopecia.
CONCLUSION
Proton therapy is an evolving cancer treatment technique that has diverse advantages over conventional radiotherapy and chemotherapy. This review provides evidence that supports that proton therapy has an improved acute toxicity profile compared to radiotherapy to treat oral and/or oropharyngeal cancer individuals.
Topics: Adult; Humans; Female; Male; Middle Aged; Aged; Proton Therapy; Oropharyngeal Neoplasms
PubMed: 36871197
DOI: 10.1111/jop.13426 -
Cancer Cell International Sep 2023In recent years, several bispecific antibodies (BsAbs) have been introduced that revolutionized the treatment approach for patients with multiple myeloma (MM). In the... (Review)
Review
BACKGROUND
In recent years, several bispecific antibodies (BsAbs) have been introduced that revolutionized the treatment approach for patients with multiple myeloma (MM). In the present study, we sought for conducting a systematic review and meta-analysis with the aim of evaluating the safety and efficacy of BsAbs in MM patients.
METHODS
PubMed, Scopus, Web of Science, and Embase databases were systematically searched on June 10, 2022. Two steps of title/abstract and full-text screening were performed for selecting the relevant articles. The primary endpoint was considered to evaluate the safety of BsAbs by examining the rate of hematologic and non-hematologic adverse effects (AEs). The secondary outcome was set at the efficacy of BsAbs through pooling objective response rate (ORR), (stringent) complete response (sCR/CR), very good partial response (VGPR), and partial response (PR).
RESULTS
Eleven publications with a total of nine evaluable BsAbs were included for qualitative and quantitative data synthesis. Hematologic AEs were more common among patients than non-hematologic events, with the most frequent events being anemia (41.4%), neutropenia (36.4%), and thrombocytopenia (26.3%). The most common non-hematological AE was infection, which occurred in 39.9% of patients, followed by dysgeusia (28.3%), fatigue (26.5%), and diarrhea (25.8%). Besides, 8.1% of patients experienced immune effector cell-associated neurotoxicity syndrome and neurotoxicity occurred in 5.1% of them. Moreover, 59.8% of patients experienced cytokine release syndrome. The pooled rate of deaths attributable to BsAbs was estimated at 0.1%. In terms of efficacy measures, the ORR was achieved in 62.6% of MM patients, and the pooled rates of sCR/CR, VGPR, and PR were 22.7%, 23.0%, and 12.1%, respectively.
CONCLUSIONS
In an era with several emerging promising treatments for MM, BsAbs have achieved a high ORR and tolerable AEs in heavily pretreated patients. However, there is still room for developing BsAbs with a lower rate of AEs and capable of bypassing tumor evasion mechanisms.
PubMed: 37670301
DOI: 10.1186/s12935-023-03045-y -
In Vivo (Athens, Greece) 2023Dysgeusia, one of the adverse effects of cancer chemotherapy, and anorexia due to taste disorder can significantly impair the quality of life of patients. However, an...
BACKGROUND/AIM
Dysgeusia, one of the adverse effects of cancer chemotherapy, and anorexia due to taste disorder can significantly impair the quality of life of patients. However, an evaluation method for dysgeusia has not yet been established. The present prospective study aimed to utilize a combination of subjective and objective assessment methods to evaluate dysgeusia in patients with gastrointestinal cancer initiating chemotherapy, to determine chemotherapeutic drugs and regimens causing dysgeusia, and to assess whether dysgeusia was associated with zinc deficiency.
PATIENTS AND METHODS
A total of 21 patients with newly diagnosed gastrointestinal cancer were registered between August 2020 to March 2021. The following regimens were also included in the evaluation if the patients did not develop dysgeusia. A total 30 regimens were administered to the patients during the study period. A salt-impregnated test paper (Salsave) was used as a subjective assessment, and the chemotherapy-induced taste alteration scale was used as an objective assessment.
RESULTS
Based on physician interviews, dysgeusia was diagnosed in 8 of 21 patients (38%) treated with 8 of 30 regimens (27%). All regimens that resulted in dysgeusia contained platinum-based drugs. The patients who developed dysgeusia had higher controlling nutritional status scores at the start of chemotherapy compared to those who did not develop dysgeusia. In both subjective and objective assessments, the patients with dysgeusia performed significantly worse than those without dysgeusia. Six of the eight patients who developed dysgeusia were administered Novelzine, which did not improve the taste disorder despite the improvement of serum zinc levels.
CONCLUSION
The combined approach using subjective and objective taste assessment methods was useful in assessing chemotherapy-induced dysgeusia. Mechanisms other than hypozincemia should be considered as contributors to taste disorders caused by platinum-based drugs.
Topics: Humans; Dysgeusia; Pilot Projects; Quality of Life; Prospective Studies; Antineoplastic Agents; Gastrointestinal Neoplasms; Taste Disorders; Zinc
PubMed: 37369461
DOI: 10.21873/invivo.13283 -
Cureus Nov 2023This article aims to ascertain the prevalence of loss of hearing in patients with chronic kidney disease (CKD) and also to examine potential causes of sensorineural... (Review)
Review
This article aims to ascertain the prevalence of loss of hearing in patients with chronic kidney disease (CKD) and also to examine potential causes of sensorineural hearing loss (SNHL) in patients suffering from CKD. It has been discovered in recent years that there is a relationship between the occurrence of SNHL and CKD. Nowadays many people are suffering from CKD. These patients deal with several otorhinolaryngological issues, such as SNHL, candidiasis, epistaxis, halitosis, dysgeusia, xerostomia, and lip and thyroid malignancies. One of the most frequent otorhinolaryngological complications is audiovestibular system impairment. There are various proposed mechanisms for the appearance of loss of hearing in people suffering from CKD. The kidney and the inner ear have multiple functional and structural similarities, which may be the cause of these problems in CKD patients. In addition, changes in the homeostasis of water and electrolytes can affect the endolymphatic fluid and result in endolymphatic hydrops. Finally, some medications, like aminoglycosides and loop diuretics, are well known for their ototoxicity and are utilized to treat patients with CKD. Only a small number of population-based research have so far been able to show a connection between CKD and audiovestibular system impairment. Some investigation has shown that CKD patients are more likely than healthy people to experience vestibular impairment. The quality of life of a patient can be reduced by hearing loss. People with hearing loss experience communication issues in daily life, which negatively affects their cognitive and psychosocial functioning. Social isolation and a poor quality of life in terms of health can all result from hearing loss. In addition, decreased renal function has also been linked to poor quality of life, hospitalization, and cognitive dysfunction.
PubMed: 38054127
DOI: 10.7759/cureus.48244 -
European Journal of Neurology Dec 2023The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), rapidly spread across the globe. Tremendous efforts have been... (Review)
Review
BACKGROUND AND PURPOSE
The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), rapidly spread across the globe. Tremendous efforts have been mobilized to create effective antiviral treatment options to reduce the burden of the disease. This article summarizes the available knowledge about the antiviral drugs against SARS-CoV-2 from a neurologist's perspective.
METHODS
We summarize neurological aspects of antiviral compounds against SARS-CoV-2 with full, conditional, or previous marketing authorization by the European Medicines Agency (EMA).
RESULTS
Nirmatrelvir/ritonavir targets the SARS-CoV-2 3c-like protease using combinatorial chemistry. Nirmatrelvir/ritonavir levels are affected by medications metabolized by or inducing CYP3A4, including those used in neurological diseases. Dysgeusia with a bitter or metallic taste is a common side effect of nirmatrelvir/ritonavir. Molnupiravir is a nucleotide analog developed to inhibit the replication of viruses. No clinically significant interactions with other drugs have been identified, and no specific considerations for people with neurological comorbidity are required. In the meantime, inconsistent results from clinical trials regarding efficacy have led to the withdrawal of marketing authorization by the EMA. Remdesivir is a viral RNA polymerase inhibitor and interferes with the production of viral RNA. The most common side effect in patients with COVID-19 is nausea. Remdesivir is a substrate for CYP3A4.
CONCLUSIONS
Neurological side effects and drug interactions must be considered for antiviral compounds against SARS-CoV-2. Further studies are required to better evaluate their efficacy and adverse events in patients with concomitant neurological diseases. Moreover, evidence from real-world studies will complement the current knowledge.
Topics: Humans; SARS-CoV-2; COVID-19; Ritonavir; Pandemics; Cytochrome P-450 CYP3A; Antiviral Agents; Drug Interactions
PubMed: 37526048
DOI: 10.1111/ene.16017 -
Journal of Infection and Public Health Dec 2023Paxlovid is an oral drug composed of nirmatrelvir and ritonavir that has been demonstrated to be effective in decreasing the risk of severe coronavirus disease 2019...
BACKGROUND
Paxlovid is an oral drug composed of nirmatrelvir and ritonavir that has been demonstrated to be effective in decreasing the risk of severe coronavirus disease 2019 (COVID-19). Here, we report the use of paxlovid in pregnant women with COVID-19.
METHODS
Pregnant women attending a tertiary referral hospital in Taiwan from 29 April to 30 July 2022 were enrolled in the study. We compared baseline characteristics, clinical manifestations, and adverse events between paxlovid-treated women and those without paxlovid use. Maternal and neonatal outcomes were analysed in women who delivered during the study period.
RESULTS
A total of 30 paxlovid-treated pregnant women and 55 women without paxlovid use were included in the analysis. The mean duration of COVID-19-associated symptoms in the paxlovid-treated women was shorter than that in the control group (10.10 days versus 15.59 days, p = 0.04). No severe adverse events due to paxlovid use were observed. Dysgeusia and diarrhoea were the most common adverse effects. Thirteen paxlovid-treated and 28 untreated women delivered during the study period. More pregnant women in the paxlovid group who delivered during the study period underwent caesarean delivery compared to the group without antiviral treatment (10 of 13 [76.92%] versus 12 of 28 [42.86%], p = 0.042), and insignificantly more newborns were born small for gestational age in the paxlovid group compared to the control group (3 of 13 [23.08%] versus 1 of 28 [3.57%], p = 0.086).
CONCLUSION
Our study showed that paxlovid was effective and safe for pregnant women during the Omicron wave of the COVID-19 pandemic. A higher proportion of caesarean delivery rates was observed among paxlovid-treated women. Long-term follow-up of pregnant women exposed to paxlovid and their offspring is needed.
Topics: Infant, Newborn; Pregnancy; Humans; Female; Ritonavir; Pandemics; COVID-19; COVID-19 Drug Treatment; Pregnant Women; Antiviral Agents
PubMed: 37871360
DOI: 10.1016/j.jiph.2023.10.007