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JAMA Network Open Oct 2023Hyponatremia and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) are associated with significant mortality and morbidity. The effectiveness and...
IMPORTANCE
Hyponatremia and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) are associated with significant mortality and morbidity. The effectiveness and safety of oral urea for SIADH are still debated.
OBJECTIVE
To evaluate the efficacy and safety of urea for the treatment of SIADH.
EVIDENCE REVIEW
A systematic search of Medline and Embase was conducted for controlled and uncontrolled studies of urea for SIADH in adult patients. The primary outcome was serum sodium concentration after treatment. Secondary outcomes included the proportion of patients with osmotic demyelination syndrome (ODS), intracranial pressure, and resource use such as length of stay.
FINDINGS
Twenty-three studies involving 537 patients with SIADH were included, of which 462 were treated with urea. The pooled mean baseline serum sodium was 125.0 mmol/L (95% CI, 122.6-127.5 mmol/L). The median treatment duration with oral urea was 5 days. Urea increased serum sodium concentration by a mean of 9.6 mmol/L (95% CI, 7.5-11.7 mmol/L). The mean increase in serum sodium after 24 hours was 4.9 mmol/L (95% CI, 0.5-9.3 mmol/L). Adverse events were few, mainly consisting of distaste or dysgeusia, and no case of ODS was reported. Resource use was too infrequently reported to be synthesized.
CONCLUSIONS AND RELEVANCE
In this systematic review of the use of urea in SIADH and despite the lack of randomized clinical trials, lower-quality evidence was identified that suggests that urea may be an effective, safe, and inexpensive treatment modality that warrants further exploration.
Topics: Adult; Humans; Urea; Inappropriate ADH Syndrome; Vasopressins; Demyelinating Diseases; Sodium
PubMed: 37902751
DOI: 10.1001/jamanetworkopen.2023.40313 -
The Journal of Allergy and Clinical... Feb 2024
Topics: Humans; Stevens-Johnson Syndrome; Dysgeusia; Olfaction Disorders
PubMed: 37898176
DOI: 10.1016/j.jaip.2023.10.036 -
The Oncologist Mar 2024Immune-related adverse events (irAEs) are common. Oral irAEs tend to cluster in patients who experience concurrent toxicities. We aimed to characterize the frequency and...
OBJECTIVES
Immune-related adverse events (irAEs) are common. Oral irAEs tend to cluster in patients who experience concurrent toxicities. We aimed to characterize the frequency and trajectory of non-oral irAEs in patients who developed oral irAEs, assess their relationship with non-oral irAEs, and compare those characteristics with patients without oral irAEs.
METHODS
A retrospective chart review was conducted to identify patients who started ICIT between December 11, 2011, and September 15, 2019 (n = 4683) in the Mass General Brigham Registered Patient Data Registry. Demographic information, cancer diagnosis, ICIT regimen, treatment duration, and time and number of infusions to irAE onset were recorded. Non-oral irAEs were categorized into 13 groups. Patients with melanoma, pulmonary cancer, or head and neck cancer who had oral irAEs were then matched with those without oral irAEs to compare the prevalence of concomitant non-oral irAEs.
RESULTS
Three hundred and fourteen patients with oral irAEs with a mean age of 65.9 ± 12.6 years (43.3% females) were included. Patients with multiple oral irAEs were more likely to have non-oral irAEs (OR: 2.7, 95% CI, 1.3-3.5), including cutaneous (OR: 1.7, 95% CI, 1.1-3.0), rheumatological (OR: 2.2, 95% CI, 1.1-4.2), thyroid (OR: 2.4, 95% CI, 1.2-4.9), and neurological irAEs (OR: 2.5, 95% CI, 1.0-6.3). Compared to matched patients with non-oral irAEs, patients with oral irAEs were more likely to have cutaneous (OR: 1.7, 95% CI, 1.0-2.8) and thyroid (OR: 2.86, 95% CI, 1.1-7.5) irAEs. The development of oral and non-oral irAEs is often coincidental.
CONCLUSION
Patients who have non-oral irAEs should be monitored for development of oral irAEs for prompt management.
Topics: Female; Humans; Middle Aged; Aged; Male; Nivolumab; Antineoplastic Agents, Immunological; Retrospective Studies; Melanoma; Lung Neoplasms
PubMed: 37874927
DOI: 10.1093/oncolo/oyad279 -
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 -
PloS One 2023Large observational studies have demonstrated the real-world effectiveness of nirmatrelvir-ritonavir in preventing severe COVID-19 in higher risk individuals, but have...
BACKGROUND
Large observational studies have demonstrated the real-world effectiveness of nirmatrelvir-ritonavir in preventing severe COVID-19 in higher risk individuals, but have provided limited information on other aspects of nirmatrelvir-ritonavir use. Our objective was to evaluate prescribing outcomes such as the prevalence of drug-drug interactions (DDI), adverse drug events (ADE) and treatment adherence in an outpatient community clinic setting.
METHODS
We conducted a single-centre retrospective cohort study of adult outpatients prescribed nirmatrelvir-ritonavir in our community COVID-19 assessment clinic in Toronto, Ontario between March 3 and September 20, 2022. We performed a descriptive analysis of the patient population, DDIs, DDI interventions, treatment adherence, ADEs and clinical outcomes of patients prescribed nirmatrelvir-ritonavir.
RESULTS
There were 637 individuals prescribed nirmatrelvir-ritonavir during the study period. The median age was 70, the median number of risk factors for severe disease were 2, 45% were immunocompromised and 82% had received 3 or more COVID-19 vaccine doses. 95% (542/572) completed the 5-day course of therapy with 68% (388/572) having complete symptom resolution by 28-day. Eleven percent (60/572) experienced recurrent symptoms following the completion of nirmatrelvir-ritonavir. Over 70% had one or more clinically significant DDIs requiring mitigation and 62% of patients experienced at least one ADE, which was most commonly dysgeusia or gastrointestinal-related. Ninety-five percent (542/572) of patients completed therapy as prescribed. Overall, hospitalization within 28 days was 3.3% with 1.2% attributed to COVID-19 and there were no deaths.
INTERPRETATION
Nirmatrelvir-ritonavir was associated with a high prevalence of clinically significant DDIs, which required mitigation strategies and a high frequency of mild ADEs. Collaborative assessment to address medication alterations resulted in high treatment adherence.
Topics: Adult; Humans; Aged; Outpatients; COVID-19; COVID-19 Vaccines; Retrospective Studies; Ritonavir; COVID-19 Drug Treatment; Didanosine; Drug-Related Side Effects and Adverse Reactions; Antiviral Agents
PubMed: 37856531
DOI: 10.1371/journal.pone.0293302 -
Cancer Medicine Oct 2023We aimed to evaluate the activity of selinexor, an oral selective inhibitor of nuclear export, in patients with recurrent or metastatic salivary gland tumors (SGT).
OBJECTIVES
We aimed to evaluate the activity of selinexor, an oral selective inhibitor of nuclear export, in patients with recurrent or metastatic salivary gland tumors (SGT).
METHODS
GEMS-001 is an open-label Phase 2 study for patients with recurrent or metastatic SGT with two parts. In Part 1 of the protocol, patients had tumor samples profiled with targeted next generation sequencing as well as immunohistochemistry for androgen receptor, HER-2 and ALK. For Part 2, patients with no targeted therapies available were eligible to receive selinexor 60 mg given twice weekly every 28 days. The primary endpoint was objective response rate. Secondary endpoints included progression-free survival (PFS) and prevalence of druggable alterations across SGT.
RESULTS
One hundred patients were enrolled in GEMS-001 and underwent genomic and immunohistochemistry profiling. A total of 21 patients who lacked available matched therapies were treated with selinexor. SGT subtypes (WHO classification) included adenoid cystic carcinoma (n = 10), salivary duct carcinoma (n = 3), acinic cell carcinoma (n = 2), myoepithelial carcinoma (n = 2), carcinoma ex pleomorphic adenoma (n = 2) and other (n = 2). Of 18 evaluable patients, stable disease (SD) was observed in 17 patients (94%) (SD ≥6 months in 7 patients (39%)). However, no objective responses were observed. The median PFS was 4.9 months (95% confidence interval, 3.4-10). The most common treatment-related Grade 1-2 adverse events were nausea [17 patients (81%)], fatigue [16 patients (76%)], and dysgeusia [12 patients (57%)]. Most common treatment-related Grade 3-4 adverse events were hyponatremia [3 patients (14%)], neutrophil count decrease [3 patients (14%)] and cataracts [2 patients (10%)]. No treatment-related deaths were observed.
CONCLUSIONS
Although tumor reduction was observed across participants, single agent selinexor anti-tumor activity was limited.
Topics: Humans; Salivary Gland Neoplasms; Hydrazines; Triazoles; Carcinoma, Acinar Cell
PubMed: 37818869
DOI: 10.1002/cam4.6589 -
JBI Evidence Synthesis Apr 2024The objective of this review is to examine the effectiveness of oral hygiene care in the management of oral symptoms in patients with cancer under specialist palliative...
OBJECTIVE
The objective of this review is to examine the effectiveness of oral hygiene care in the management of oral symptoms in patients with cancer under specialist palliative care and the patients' experience of such symptoms and care.
INTRODUCTION
Oral symptoms, such as xerostomia, mouth pain, or dysgeusia, are highly prevalent in patients with cancer under specialist palliative care. These symptoms have a negative effect on patients' quality of life. Oral hygiene care can manage oral symptoms and could be improved with a more systematized approach, adequate guidelines, and training to properly integrate oral hygiene into the care provided in specialist palliative care.
INCLUSION CRITERIA
This review will consider quantitative, qualitative, and mixed methods studies on the effectiveness and experience of oral hygiene care intended to manage oral symptoms in patients with cancer aged 18 years or older, diagnosed with any type of cancer, under specialist palliative care.
METHODS
The search will be conducted in MEDLINE (PubMed), CINAHL (EBSCOhost), Cochrane Central Register of Controlled Trials, Dentistry and Oral Sciences Source (EBSCOhost), and MedicLatina (EBSCOhost). Sources of unpublished studies and gray literature to be searched will include Networked Digital Library of Theses and Dissertations and Repositórios Científicos de Acesso Aberto de Portugal. Studies in English, Portuguese, and Spanish published from 2000 to the present will be considered. Methodological quality of included studies will be assessed and data will be extracted. Synthesis and integration will follow the JBI segregated approach for mixed methods reviews.
REVIEW REGISTRATION
PROSPERO CRD42023400554.
Topics: Humans; Palliative Care; Oral Hygiene; Quality of Life; Systematic Reviews as Topic; Neoplasms; Review Literature as Topic
PubMed: 37791797
DOI: 10.11124/JBIES-23-00096 -
Cancers Sep 2023Post-oropharyngeal cancer treatment complications include a multitude of oral side effects that impact overall survival and quality of life. These include acute and... (Review)
Review
Post-oropharyngeal cancer treatment complications include a multitude of oral side effects that impact overall survival and quality of life. These include acute and chronic conditions affecting the oral cavity and head and neck, such as mucositis, infection, xerostomia, dysgeusia, radiation caries, osteonecrosis, and trismus. This review will summarize the most common oral complications from oropharyngeal cancer therapy. The authors would like to point out that the literature cited frequently combines oropharyngeal and head and neck cancer results. If recommendations are made strictly related to oropharyngeal cancers, this will be highlighted.
PubMed: 37760517
DOI: 10.3390/cancers15184548 -
BMC Oral Health Sep 2023Early studies have highlighted the possible development of dysgeusia and anosmia in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and these...
BACKGROUND
Early studies have highlighted the possible development of dysgeusia and anosmia in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and these manifestations should be considered a potential indication of coronavirus disease 19 (COVID-19). As potential contributors to these symptoms, dentists should perform careful oral and oropharyngeal examinations and document suspicious oral lesions in patients with COVID-19, especially in those who complain of loss of taste and smell. The study's objective was to assess the prevalence of oral manifestations among ambulatory unvaccinated symptomatic patients with suspected COVID-19 during the acute phase of the disease.
METHODS
This cross-sectional study evaluated oral manifestations in adults (aged ≥ 18 years) with suspected and confirmed SARS-CoV-2 infection. Chi-square and Fisher's exact tests were used to compare data between the groups (rRT-PCR-positive and rRT-PCR-negative patients).
RESULTS
One hundred thirty-six participants were included. Most were female (n = 79; 58.1%), with a mean age of 39.53 (± 14.17) years. Of these, 54 (39.7%) had a positive rRT-PCR test, and 82 (60.3%) had negative rRT-PCR results. Oral manifestations were observed in 40 participants (74.1%) in the rRT-PCR-positive group and 67 participants (81.7%) in the rRT-PCR-negative group. The most common oral manifestations were xerostomia (n = 85; 62.5%) and dysgeusia/ageusia (n = 57; 41.9%). Different rates of gingivitis (n = 12; 22.2% vs. n = 5; 6.1%; p = 0.005) and halitosis (n = 7; 13.0% vs. n = 1; 1.2%; p = 0.007) were observed between the rRT-PCR-positive and -negative groups, respectively. Mouth ulcers, glossitis, tongue coating, and petechiae were reported in both groups without significant differences.
CONCLUSIONS
A high prevalence of oral manifestations was observed in symptomatic patients with suspected or confirmed COVID-19.
CLINICAL RELEVANCE
This study highlights the importance of routine oral examinations by dentists as part of the multidisciplinary care of COVID-19 patients.
Topics: Adult; Humans; Female; Male; COVID-19; SARS-CoV-2; Cross-Sectional Studies; Dysgeusia; Polymerase Chain Reaction
PubMed: 37759210
DOI: 10.1186/s12903-023-03325-z -
International Journal of Radiation... Mar 2024DNA-dependent protein kinase (DNA-PK) plays a key role in the repair of DNA double strand breaks via nonhomologous end joining. Inhibition of DNA-PK can enhance the...
PURPOSE
DNA-dependent protein kinase (DNA-PK) plays a key role in the repair of DNA double strand breaks via nonhomologous end joining. Inhibition of DNA-PK can enhance the effect of DNA double strand break inducing anticancer therapies. Peposertib (formerly "M3814") is an orally administered, potent, and selective small molecule DNA-PK inhibitor that has demonstrated radiosensitizing and antitumor activity in xenograft models and was well-tolerated in monotherapy. This phase 1 trial (National Clinical Trial 02516813) investigated the maximum tolerated dose, recommended phase 2 dose (RP2D), safety, and tolerability of peposertib in combination with palliative radiation therapy (RT) in patients with thoracic or head and neck tumors (arm A) and of peposertib in combination with cisplatin and curative-intent RT in patients with squamous cell carcinoma of the head and neck (arm B).
METHODS AND MATERIALS
Patients received peposertib once daily in ascending dose cohorts as a tablet or capsule in combination with palliative RT (arm A) or in combination with intensity modulated curative-intent RT and cisplatin (arm B).
RESULTS
The most frequently observed treatment-emergent adverse events were radiation skin injury, fatigue, and nausea in arm A (n = 34) and stomatitis, nausea, radiation skin injury, and dysgeusia in arm B (n = 11). Based on evaluations of dose-limiting toxicities, tolerability, and pharmacokinetic data, RP2D for arm A was declared as 200 mg peposertib tablet once daily in combination with RT. In arm B (n = 11), 50 mg peposertib was declared tolerable in combination with curative-intent RT and cisplatin. However, enrollment was discontinued because of insufficient exposure at that dose, and the RP2D was not formally declared.
CONCLUSIONS
Peposertib in combination with palliative RT was well-tolerated up to doses of 200 mg once daily as tablet with each RT fraction. When combined with RT and cisplatin, a tolerable peposertib dose yielded insufficient exposure.
Topics: Humans; Cisplatin; Protein Kinase Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Head and Neck Neoplasms; Nausea; Tablets; DNA; Pyridazines; Quinazolines
PubMed: 37751793
DOI: 10.1016/j.ijrobp.2023.09.024