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Journal of Patient-reported Outcomes Dec 2023Understanding patients' perspectives regarding drug tolerability, in addition to effectiveness, provides a complete picture of the patient experience and supports more...
Use of the National Cancer Institute Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events to assess treatment tolerability in pulmonary arterial hypertension: qualitative patient research findings in current and former users of oral selexipag.
BACKGROUND
Understanding patients' perspectives regarding drug tolerability, in addition to effectiveness, provides a complete picture of the patient experience and supports more informed therapeutic decision-making. The item library of the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) was developed to measure patient-reported frequency, severity, and interference of adverse events (AEs) associated with cancer therapies. This qualitative interview study assessed the suitability of items selected from the PRO-CTCAE library for assessing tolerability of selexipag, a medication targeting the prostacyclin pathway for patients with pulmonary arterial hypertension (PAH).
METHODS
Two rounds of 10 qualitative, web-assisted telephone interviews following a semi-structured guide were conducted in individuals with recent experience taking oral selexipag for PAH. Each interview included concept elicitation to gather participants' perspectives on symptomatic AEs (type, frequency, severity, and interference) and cognitive debriefing of PRO-CTCAE items addressing the most frequently reported AEs of oral selexipag.
RESULTS
Interviews were conducted with 20 participants with PAH (mean [range] age 50 [24-68] years; 75% female; 85% in World Health Organization Functional Class II-III), comprising different races/ethnicities, levels of education, and employment status. Fifteen participants were currently treated with selexipag; five had taken selexipag for ≥ 6 months before discontinuing. The most frequently reported AEs included headache, jaw pain, and nausea (n = 15, 12, and 10 participants, respectively). Diarrhea and headache were identified as the most bothersome AEs by 5 and 4 participants, respectively. Some AEs were transitory (e.g., jaw pain); others were long-lasting (e.g., muscle pain). Based on findings from Round 1 interviews, a flushing item was added and the PRO-CTCAE general pain item was modified to be specific to jaw pain for testing in Round 2. Interview findings identified the following AEs as relevant to assess in a PAH clinical trial: nausea, vomiting, diarrhea, flushing, jaw pain, headache, aching muscles, and aching joints.
CONCLUSIONS
The PRO-CTCAE items selected in this study and the additional symptomatic AEs identified as patient-relevant have the potential to be included in assessments capturing the patient perspective on tolerability in future studies of selexipag and possibly other PAH therapies.
Topics: United States; Humans; Female; Middle Aged; Male; Pulmonary Arterial Hypertension; National Cancer Institute (U.S.); Familial Primary Pulmonary Hypertension; Pain; Diarrhea; Headache; Nausea; Neoplasms
PubMed: 38108945
DOI: 10.1186/s41687-023-00673-w -
Cureus Nov 2023The benign tumor central odontogenic fibroma (COF) accounts for less than 1% of all the existing odontogenic tumors. The mandibular or maxillary cortical plate is seen...
The benign tumor central odontogenic fibroma (COF) accounts for less than 1% of all the existing odontogenic tumors. The mandibular or maxillary cortical plate is seen to show asymptotic diversification. It has been characterized as a benign jaw neoplasm. Radiographically, it primarily manifests as a multilocular radiolucency. Histologically, it comprises fibroblasts and mature collagen fibers. The popular choice for the management of COFs is enucleation, followed by the extraction of associated teeth. COFs have maintained a track record of showing rare chances of recurrence following surgery. COF was detected in a 38-year-old female who had edema in the lower right front tooth region. The lesion was surgically removed, and a histopathological examination was performed. Many case reports of COF have been stated in the literature. This indicates that cases of COF are not a rare appearance.
PubMed: 38098899
DOI: 10.7759/cureus.48772 -
Journal of Plastic, Reconstructive &... Jan 2024A real-time 3D Telemedicine system - leveraging Microsoft's Holoportation™ communication technology - enabled an international multidisciplinary team meeting...
UNLABELLED
A real-time 3D Telemedicine system - leveraging Microsoft's Holoportation™ communication technology - enabled an international multidisciplinary team meeting (MDT) to consult with complex reconstructive patients before, during, and after an overseas surgical collaboration.
METHODS
A proof-of-concept international 3D MDT clinic took place in November 2022, between the Canniesburn Plastic Surgery Unit, UK, and the National Reconstructive Plastic Surgery and Burns Centre, Korle Bu Teaching Hospital, Ghana. The 3D system was utilised 1) previsit to assess patients and enable logistical planning, 2) on-site in Ghana to further allow patients to see themselves and proposed operations in 3D, and 3) post visit to debrief the team and patients.
RESULTS
Four Ghana patients were followed through their patient journey (mandibular ameloblastoma, sarcoma thigh, maxillary tumour, sarcoma back). Thirteen participants (four patients, four Ghana clinicians, and five UK clinicians) completed feedback on the 3D MDT. Outcome measures were rated highly with satisfaction 84.31/100, perceived benefit 4.54/5, overall quality 127.3/147 (Telehealth Usability Questionnaire), and usability 83.2/100 (System Usability Scale). These data show close alignment with that previously published on high-income countries.
CONCLUSIONS
This novel technology has the potential to enhance the delivery of overseas surgical visits to low-to-middle-income countries, by improving planning, informed discussion with patients, expert consensus on complex cases, and fostering engagement with professionals who may be thousands of miles away. This is the first demonstration that real-time 3D Telemedicine can both work, and enhance care within an international MDT clinic, and may thus enable change in the approach to overseas surgical collaborations.
Topics: Humans; Ghana; Maxillary Neoplasms; Hospitals, Teaching; Telemedicine; Sarcoma
PubMed: 38091684
DOI: 10.1016/j.bjps.2023.10.130 -
Hormones (Athens, Greece) Mar 2024Primary hyperparathyroidism (PHPT), a relatively common disorder characterized by hypercalcemia with raised or inappropriately normal serum parathyroid hormone (PTH)... (Review)
Review
Primary hyperparathyroidism (PHPT), a relatively common disorder characterized by hypercalcemia with raised or inappropriately normal serum parathyroid hormone (PTH) concentrations, may occur as part of a hereditary syndromic disorder or as a non-syndromic disease. The associated syndromic disorders include multiple endocrine neoplasia types 1-5 (MEN1-5) and hyperparathyroidism with jaw tumor (HPT-JT) syndromes, and the non-syndromic forms include familial hypocalciuric hypercalcemia types 1-3 (FHH1-3), familial isolated hyperparathyroidism (FIHP), and neonatal severe hyperparathyroidism (NS-HPT). Such hereditary forms may occur in > 10% of patients with PHPT, and their recognition is important for implementation of gene-specific screening protocols and investigations for other associated tumors. Syndromic PHPT tends to be multifocal and multiglandular with most patients requiring parathyroidectomy with the aim of limiting end-organ damage associated with hypercalcemia, particularly osteoporosis, nephrolithiasis, and renal failure. Some patients with non-syndromic PHPT may have mutations of the MEN1 gene or the calcium-sensing receptor (CASR), whose loss of function mutations usually cause FHH1, a disorder associated with mild hypercalcemia and may follow a benign clinical course. Measurement of the urinary calcium-to-creatinine ratio clearance (UCCR) may help to distinguish patients with FHH from those with PHPT, as the majority of FHH patients have low urinary calcium excretion (UCCR < 0.01). Once genetic testing confirms a hereditary cause of PHPT, further genetic testing can be offered to the patients' relatives and subsequent screening can be carried out in these affected family members, which prevents inappropriate testing in normal individuals.
Topics: Infant, Newborn; Humans; Hyperparathyroidism, Primary; Calcium; Hypercalcemia; Adenoma; Fibroma; Hyperparathyroidism; Jaw Neoplasms
PubMed: 38038882
DOI: 10.1007/s42000-023-00508-9 -
Frontiers in Pharmacology 2023To investigate adverse events (AEs) associated with denosumab (Dmab) and zoledronic acid (ZA), compare their association strengths, and explore potential applications...
To investigate adverse events (AEs) associated with denosumab (Dmab) and zoledronic acid (ZA), compare their association strengths, and explore potential applications to provide clinical reference. We collected data from FAERS from January 2004 to November 2022 and mined AE signals for Dmab and ZA using ROR values. We compared signal intensity for same AEs and investigated off-label use. We also examined their AEs in adjuvant therapy for breast and prostate cancer. 154,735 reports of primary suspect drugs were analyzed in the FAERS database (Dmab: 117,857; ZA: 36,878). Dmab and ZA had 333 and 1,379 AE signals, with 189 overlaps. The AEs of Dmab included death (ROR:3.478), osteonecrosis of jaw (ROR:53.025), back pain (ROR:2.432), tooth disorder (ROR:16.18), bone pain (ROR:6.523). For ZA, the AEs included osteonecrosis (ROR:104.866), death (ROR: 3.645), pain (ROR:3.963), osteonecrosis of jaw (ROR: 91.744), tooth extraction (ROR: 142.143). Among overlap signals, Dmab showed higher strength in exostosis of the jaw (ROR: 182.66 vs. 5.769), atypical fractures (ROR: 55.589 vs. 9.123), and atypical femur fractures (ROR:49.824 vs. 4.968). And ZA exhibited stronger associations in abscess jaw (ROR: 84.119 vs. 11.12), gingival ulceration (ROR: 74.125 vs. 4.827), increased bone formation (ROR: 69.344 vs. 3.218). Additionally, we identified 528 off-label uses for Dmab and 206 for ZA, with Dmab mainly used in prostate cancer (1.04%), breast cancer (1.03%), and arthritis (0.42%), while ZA in breast cancer (3.21%), prostate cancer (2.48%), and neoplasm malignant (0.52%). For Dmab in breast cancer treatment, AEs included death (11.6%), disease progression (3.3%), and neutropenia (2.7%), while for ZA included death (19.8%), emotional disorder (12.9%), osteomyelitis (11.7%). For prostate cancer treatment, Dmab`s AEs were death (8.9%), prostate cancer metastatic (1.6%), renal impairment (1.7%), while ZA`s included death (34.4%), general physical health deterioration (19.9%), and hemoglobin decreased (18.9%). Our analysis of FAERS database provided postmarketing surveillance data and revealed different strengths of reported AE signals between Dmab and ZA in some of their common AEs. It's also worth noting that both drugs have potential off-label applications, which could introduce new AEs. This highlights the necessity for safety monitoring when using Dmab and ZA off-label.
PubMed: 38027014
DOI: 10.3389/fphar.2023.1225919 -
Cureus Oct 2023Ameloblastoma is one of the most prevalent but enigmatic benign odontogenic tumors of the jaw, accounting for approximately 10% of all maxillary and mandibular tumors.... (Review)
Review
Ameloblastoma is one of the most prevalent but enigmatic benign odontogenic tumors of the jaw, accounting for approximately 10% of all maxillary and mandibular tumors. This neoplasia is distinguished by exhibiting several clinical and histological variants along with several mutations that affect its behavior. The ameloblastoma treatment plan is determined by the tumor's size, anatomical location, histologic variant, and anatomical involvement. On chromosome 7, there is a proto-oncogene called BRAF. When BRAF is mutated, it becomes an oncogene and continuously produces proteins like MEK and ERK, members of mitogen-activated protein kinase (MAPK). In the signaling pathway, these proteins activate transcription factor inside the nucleus that helps in cell division and growth. Numerous neoplasms have been linked to more than 40 BRAF mutations. The most common one is BRAF proto-oncogene serine/threonine kinase (BRAF) V600E, whose treatment has been linked to a positive outcome. BRAF inhibitors like vemurafenib, dabrafenib, and sorafenib have shown excellent results, especially in metastatic ameloblastoma. BRAF, particularly in the case of metastatic ameloblastoma, inhibitors such as vemurafenib, dabrafenib, and sorafenib, has demonstrated outstanding results. Targeted therapies have been employed as adjuvant therapies to enhance cosmetic outcomes, even though no reports of serial cases demonstrate their effectiveness in ameloblastomas. In the treatment of ameloblastomas, the identification of BRAF V600E and additional mutations as the prime targeted therapies has proven to be a significant breakthrough where surgical treatment was contraindicated. In this article, we review the presence of BRAF V600E mutations, their inhibitors, and targeted therapies in ameloblastoma.
PubMed: 38021761
DOI: 10.7759/cureus.47682 -
Medicina (Kaunas, Lithuania) Nov 2023Hepatocellular carcinoma (HCC) most frequently metastasizes in the lungs, abdominal lymph nodes and adrenal glands. Metastatic spread to the head and neck area is...
A Rare Case of Isolated Hepatocellular Carcinoma Metastasis in Left Mandibular Region in a Patient with Hepatitis C Virus Liver Cirrhosis Diagnosed after the Onset of COVID-19 Infection.
Hepatocellular carcinoma (HCC) most frequently metastasizes in the lungs, abdominal lymph nodes and adrenal glands. Metastatic spread to the head and neck area is extremely rare. In the presented case, an uncommon site of solitary metastatic spread of HCC to the mandible confirmed after the core biopsy of the lesion is reported. There have been only about 80 cases of mandibular HCC metastases described in the literature to date. We contribute our experience to the pool of data. A 65-year-old female with HCV-related liver cirrhosis was diagnosed with an HCC that was successfully treated with liver resection. Subsequently, the patient had developed COVID-19 disease, which was associated with a painless swelling in the left jaw. A neck MDCT scan demonstrated an osteolytic soft-tissue mass in the left mandible, with the characteristics consistent for the metastasis of HCC. In order to confirm the diagnosis, a core biopsy of the mandibular mass was performed. The pathohistological evaluation confirmed the presence of a metastatic HCC in the mandible. No other sites of disease dissemination were identified in extensive MDCT scans. Despite considering various treatments, including symptomatic and palliative, the patient's overall prognosis remained poor. Isolated metastases of HCC to the orofacial region are extremely rare; however, it should be considered in patients with known risk factors for HCC development. Early diagnosis is critical, and clinicians should consider this possibility of HCC spread when assessing patients with orofacial swelling, among those patients with risk factors for HCC. The overall prognosis for such patients remains poor, emphasizing the challenges in managing these cases.
Topics: Female; Humans; Aged; Carcinoma, Hepatocellular; Liver Neoplasms; Hepacivirus; COVID-19; Hepatitis C; Liver Cirrhosis
PubMed: 38004041
DOI: 10.3390/medicina59111992 -
Medicina (Kaunas, Lithuania) Nov 2023Ameloblastoma is the most common benign odontogenic tumor with local invasion and high recurrence, which generally occurs in the jaw bones. Hypercalcemia is a common... (Review)
Review
Ameloblastoma is the most common benign odontogenic tumor with local invasion and high recurrence, which generally occurs in the jaw bones. Hypercalcemia is a common paraneoplastic syndrome that is commonly observed in patients with malignancies but rarely encountered in patients with benign tumors. Thus far, not many cases of ameloblastoma with hypercalcemia have been reported, and the pathogenic mechanism has not been studied in depth. This paper presents a case report of a 26-year-old male diagnosed with giant ameloblastoma of the mandible, accompanied by rare hypercalcemia. Additionally, a review of the relevant literature is conducted. This patient initially underwent marsupialization, yet this treatment was not effective, which indicated that the selection of the appropriate operation is of prime importance for improving the prognosis of patients with ameloblastoma. The tumor not only failed to shrink but gradually increased in size, accompanied by multiple complications including hypercalcemia, renal dysfunction, anemia, and cachexia. Due to the contradiction between the necessity of tumor resection and the patient's poor systemic condition, we implemented a multi-disciplinary team (MDT) meeting to better evaluate this patient's condition and design an individualized treatment strategy. The patient subsequently received a variety of interventions to improve the general conditions until he could tolerate surgery, and finally underwent the successful resection of giant ameloblastoma and reconstruction with vascularized fibular flap. No tumor recurrence or distance metastasis was observed during 5 years of follow-up. Additionally, the absence of hypercalcemia recurrence was also noted.
Topics: Male; Humans; Adult; Ameloblastoma; Hypercalcemia; Mandibular Neoplasms; Neoplasm Recurrence, Local; Mandible
PubMed: 38004005
DOI: 10.3390/medicina59111956 -
Mechanisms of Ageing and Development Dec 2023The naked mole-rat (NMR) Heterocephalus glaber (from the Greek/latin words ἕτερος, heteros = divergent, κεφαλή, kephalē = head and glabra = hairless) was... (Review)
Review
The naked mole-rat (NMR) Heterocephalus glaber (from the Greek/latin words ἕτερος, heteros = divergent, κεφαλή, kephalē = head and glabra = hairless) was first described by Rüppell (Fig. 1) and belongs to the Hystricognath (from the Greek words ὕστριξ, hystrix = porcupine and γνάθος, gnathos = jaw) as a suborder of rodents. NMR are characterized by the highest longevity among rodents and reveal a profound cancer resistance. Details of its skin-specific protective and resistance mechanisms against aging and carcinogenesis have so far not been adequately characterized. Recently, our knowledge of NMR skin biology was complemented and expanded by published data using state-of-the art histological and molecular techniques. Here we review and integrate novel published data regarding skin morphology and histology of the aging NMR and the underlying mechanisms at the cellular and molecular level. We relate this data to the longevity of the NMR and its resistance to neoplastic transformation and discuss further open questions to understand its extraordinary longevity. In addition, we will address the exposome, defined as "the total of all non-genetic, endogenous and exogenous environmental influences" on the skin, respiratory tract, stomach, and intestine. Finally, we will discuss in perspective further intriguing possibilities arising from the interaction of skin with other organs.
Topics: Animals; Resilience, Psychological; Aging; Longevity; Neoplasms; Mole Rats
PubMed: 37993056
DOI: 10.1016/j.mad.2023.111887 -
BMC Oral Health Nov 2023Patients with mandibular conventional ameloblastoma undergoing radical surgical treatment experience greater trauma and often find it challenging to accept, whereas...
BACKGROUND
Patients with mandibular conventional ameloblastoma undergoing radical surgical treatment experience greater trauma and often find it challenging to accept, whereas conservative therapy is associated with a higher recurrence rate. In this study, we have improved traditional conservative treatment for mandibular conventional ameloblastoma by curettage combined with bone cavity opening (Cur/BCO). This retrospective study aimed to evaluate the effectiveness of the Cur/BCO treatment by comparing its recurrence rate and bone mineral density (BMD) growth rate with the traditional conservative treatment approach.
METHODS
A total of 40 patients, meeting the study's inclusion and exclusion criteria from 2012 to 2020, were screened, with 20 in the modified group and 20 in the traditional group. ImageJ (RRID: SCR_003070) software was employed for measuring image indices. All data were analyzed using T-test, Chi-square test and Fisher exact test in SPSS 26.0 (p = 0.05).
RESULTS
The incidence of recurrence was significantly lower in the modified group, at only 5%, compared to 35% in the traditional group (p < 0.05). Regarding bone mineral density (BMD) growth rate, the average value in the modified group was 0.0862 ± 0.2302 (/month), significantly higher than the average value of 0.0608 ± 0.2474 (/month) in the traditional group (p < 0.05).
CONCLUSIONS
In this study, it was found that the recurrence rate of the modified conservative treatment (Cur/BCO) was lower than that of the traditional conservative treatment for managing mandibular conventional ameloblastoma. Furthermore, the BMD growth rate was quicker in the modified group. Thus, Cur/BCO could be considered as a viable option for the conservative treatment of mandibular conventional ameloblastoma.
Topics: Humans; Ameloblastoma; Retrospective Studies; Mandibular Neoplasms; Neoplasm Recurrence, Local; Mandible; Curettage
PubMed: 37986074
DOI: 10.1186/s12903-023-03660-1