Eustachian Tube Dysfunction Diagnostic Pathway-What Is the Current State of the Art and How Relevant Is Chronic Nasal Disease?

Background: Eustachian tube dysfunction (ETD) presents a complex diagnostic challenge in otolaryngology, compounded by its multifaceted nature and overlapping symptoms with chronic nasal disease. This article examines the intricacies of ETD diagnosis, emphasising the necessity for a consensus on diagnostic procedures. Methods: A review of the literature was performed through the OVID research tool in the Pubmed/Medline databases to identify relevant articles that discuss eustachian tube dysfunction diagnostics as well as its correlation with chronic nasal disease. Results: The literature review harvested 201 articles, and only 51 of them were included in the full text review. A consensus statement was identified on eustachian tube dysfunction, function and diagnostics. It appears that there is significant variability in the diagnostic tools used to identify eustachian tube dysfunction. The main diagnostic approaches used are tympanometry, tubomanometry and sonotubometry, combined with the Patient-Reported Outcome Measure ETDQ-7 questionnaire to support the diagnosis of the condition. Nasal pathology is mostly absent from the retrieved studies, while ear pathology is more commonly mentioned in the current literature. Conclusions: There is no gold standard diagnostic tool to determine the presence of eustachian tube dysfunction. Further discussion, large multicentre studies and focused research are required to achieve a consensus on a diagnostic approach. The authors suggest a diagnostic pathway that combines subjective and objective diagnostic tools to determine the presence of eustachian tube dysfunction. This pathway is simple and can be used in district ENT departments, highlighting the nasal pathology relevance to ETD.

The Relationship Between the Retromandibular Vein and the Extratemporal Segment of the Facial Nerve: A Prospective Cadaveric Study of 24 Hemifaces.

INTRODUCTION: Anatomical preservation and functional integrity of the facial nerve (FN) are the main concerns of parotid surgery. Even though a variety of anatomical landmarks have been proposed and widely utilized, temporal or permanent postoperative FN palsy is still a significant comorbidity of parotid surgery. Therefore, the literature must fully elucidate the consistency of the anatomical relationship between the FN and the retromandibular vein (RMV). METHODS: We conducted a cadaveric study of 24 hemifaces to map the relationship between the FN and the RMV. Three distinct patterns were identified. Fourteen of the hemifaces were males, and 10 were females. Thirteen cadaveric dissections were performed on the right side and 11 on the left side. RESULTS: Our study found three distinct patterns and proposed a classification system. Type I (66.7%) is when the nerve lies exclusively lateral to the RMV. Type II (29.2%) is when the FN lies superficial to the RMV, but its mandibular branch lies deep to the anterior branch of the RMV, and type III (4.1%) is when the FN lies exclusively medial to the RMV. CONCLUSION: The FN and RMV relationship is not constant, and surgeons should be aware of every anatomical variation. Especially in cases where the FN is estimated to lie more in-depth to the level of the RMV, a retrograde approach may be required to avoid a FN injury.

Prelaminated Nose Reconstruction: Comparison of Forehead and Radial Donor Site and Review of the Literature.

INTRODUCTION: Total nose reconstruction is demanding as it is a 3-dimensional structure that needs lining, support and external coverage. Usually, several stages are needed to achieve a satisfactory result. The authors present 2 cases of prelaminated radial forearm and 2 prelaminated forehead nose reconstructions and compare both methods. According to our review of the literature, this is the first report of prelaminated forehead for total nose reconstruction. MATERIALS AND METHODS: The last 5 years the authors have treated 4 patients with prelaminated flaps for total nose reconstruction. The age ranged from 50 to 75 years. There were 3 male patients and one female. Three patients underwent total nose amputation due to squamous cell carcinoma and one due to melanoma. RESULTS: Two patients were treated with prelaminated radial forearm reconstruction and 2 with prelaminated forehead reconstruction. Both patients that were treated with prelaminated radial forearm reconstruction had the collapse of the nasal pyramid and had salvage procedures with replacement of the cartilaginous framework with iliac bone graft framework. CONCLUSIONS: Prelaminated nose reconstruction with either the radial forearm or forehead flap needs several stages. There is the possibility of infection-collapse of the cartilage framework, therefore, the authors recommend reconstruction of the nasal skeleton with an iliac bone graft. The flaps are stiff and difficult to handle. The authors don't think that prelaminated nose reconstruction with the radial forearm flap has advantage compared with the classic several stages nose reconstruction with radial forearm flap. Possibly, prelaminated forehead reconstruction can be applied for aged patients who cannot undergo microsurgical reconstruction.

The impact of submucosal PRP injection on wound healing after endoscopic sinus surgery: a randomized clinical trial.

PURPOSE: Chronic rhinosinusitis (CRS) is a prevalent chronic disease observed on a global scale. The utilization of endoscopic sinus surgery (ESS) has gained significant recognition as an effective intervention for individuals with CRS and nasal polyps who have not responded to conventional treatments. The need (or not) for revision surgery frequently relies on the promotion of optimal wound healing. The impact of platelet-rich plasma (PRP) on tissue healing has been extensively examined in various surgical fields. METHODS: The present prospective study involved 30 patients suffering with nasal polyposis who underwent endoscopic sinus surgery. 15 patients were assigned to the PRP group, and 15 patients to the control group. The clinical follow-up of the patients took place at specific intervals, at weeks 1, 2, 3, 4, 8, and 12 after the surgical procedure. The evaluator identified the existence of adhesions, crusting, bleeding, granulation and infection using a visual analogue scale score. The patients also completed the SNOT 22 questionnaire prior to surgery and at each postoperative visit. RESULTS: The present study observed a lower incidence of adhesion, infection, hemorrhage and granulation in the PRP group. Furthermore, a statistically significant difference was detected between the groups. CONCLUSION: Based on the findings of the present investigation, it seems that platelet-rich plasma (PRP) is beneficial on wound healing during the early stages following the surgical procedure. The technique is characterized by its limited invasiveness, which contributes to its low risk profile and the achievement of clinically good outcomes.

Posterior epistaxis management: review of the literature and proposed guidelines of the hellenic rhinological-facial plastic surgery society.

PURPOSE: Posterior epistaxis is a common emergency in ENT practice varying in severity and treatment. Many management guidelines have been proposed, all of which are a product of retrospective analyses due to the nature of this pathology, as large-scale double-blind studies are impossible-even unethical-to conduct. The purpose of this review is to perform a thorough analysis and comparison of every treatment plan available and establish guidelines for the best possible outcome in accordance to every parameter studied. Given the extensive heterogeneity of information and the multitude of studies on this topic, along with the comparison of various treatment options, we opted for a literature review as our research approach. METHODS: A review of the literature was performed using PubMed Database and search terms included "posterior epistaxis", "treatment", "management", "guidelines", "algorithm" "nasal packing", "posterior packing", "surgery", "SPA ligation", "embolization", "risk factors" or a combination of the above. RESULTS: Initial patients' assessment invariably results in most cases in posterior packing. There seems to be a superiority in recent literature of early surgery over nasal packing as a definitive treatment. Embolization is usually used after surgery failure, except for specific occasions. CONCLUSION: Despite the vast heterogeneity of information, there seems to be a need for re-evaluation of the well-established treatment plans according to more recent studies.

Improvement of the aerobic performance in endurance athletes presenting nasal valve compromise with the application of an internal nasal dilator.

PURPOSE: We investigated the effects of an internal nasal dilator on nasal airflow and cardio-respiratory capacity in adult endurance athletes, while performing controlled exhaustive physical exercise. METHODS: Prospective observational study. Participants were 38 adult endurance athletes, 23 with and 15 without nasal valve compromise. Nasal patency was objectively evaluated with anterior rhinomanometry, acoustic rhinometry and peak nasal inspiratory flow (PNIF). Maximum oxygen uptake (VO2max), maximum pulmonary ventilation, time to exhaustion and total time of nasal respiration were recorded during a submaximal treadmill test. Dyspnea intensity and fatigue perception were evaluated using a labeled visual analog scale. All assessments were performed with and without the application of the internal nasal dilator. RESULTS: All the parameters related to aerobic capacity were significantly reduced in the group of athletes with nasal valve compromise (p. <0.05 for all variables). The internal nasal dilator improved statistically significantly the nasal patency (p. <0.001), VO2max and aerobic performance and self-rating of dyspnea and fatigue (p. <0.05 for all parameters) only in athletes with nasal obstruction. PNIF correlated significantly with VO2max (rho = 0.4, p. <0.05). CONCLUSIONS: Internal nasal dilation improves nasal patency and aerobic performance during submaximal exercise in adult endurance athletes with nasal obstruction symptoms due to nasal valve compromise.

The role of rigid laryngo-tracheo-bronchoscopy in children with obstructive sleep apnoea: a case series of 65 children.

OBJECTIVE: To assess the role of laryngo-tracheo-bronchoscopy in children with obstructive sleep apnoea by identifying airway abnormalities at surgery, that occur separately or in addition to adenotonsillar hypertrophy, and examining the correlation with respiratory parameters. METHODS: A retrospective study was conducted of children with obstructive sleep apnoea who underwent laryngo-tracheo-bronchoscopy intra-operatively, performed by a single ENT surgeon from February 2016 to July 2019. Pre- and post-operative minimum oxygen saturation, apnoea-hypopnoea index, and oxygen desaturation index were recorded. RESULTS: Sixty-five children were identified; 34 were aged less than three years and 31 were aged three years or more. 77 per cent and 13 per cent respectively had an airway abnormality; the t-test showed a significantly higher mean oxygen desaturation index and lower mean minimum oxygen saturation pre-operatively compared to children without an airway abnormality. CONCLUSION: An update of the surgical pathway for children aged less than three years with obstructive sleep apnoea is required to include laryngo-tracheo-bronchoscopy intra-operatively. A t-test analysis of the pre-operative respiratory parameters suggests that airway abnormalities contribute to obstructive sleep apnoea severity.

Efficacy of High-Intensity Training in Patients with Moderate to Severe Dysphagia after Glossectomy.

Dysphagia is the main impairment arising from glossectomy for tongue cancer treatment. The study aimed to determine if an eight-week training protocol paired with accuracy tasks and swallowing exercises is effective and can improve tongue strength and swallowing in patients after tongue resection. Maximum isometric pressures, tongue endurance, swallowing pressures, mealtime duration, and oropharyngeal swallow function were studied in patients with moderate to severe dysphagia after glossectomy. Twenty-five (25) patients and thirty-one (31) healthy participants were enrolled in the study. The therapy group (TG) consisted of seventeen (17) patients who followed an 8-week treatment protocol and had multiple measurements. The follow-up control group (FUG) consisted of eight non-treated patients who had a baseline and an 8-week follow-up examination. Healthy participants served as the reference group (RF). Maximum isometric pressures, endurance, and swallowing pressures increased significantly in the TG versus the FUG. Significant improvement was documented in the TG regarding the EAT-10 questionnaire, the Penetration-Aspiration Scale scores at thickened and solid boluses, and post-swallow residues at thickened and solid boluses. The treatment protocol with tongue strength exercises combined with accuracy tasks and swallowing exercises improves the post-operative swallowing function in patients after glossectomy. Patients in the TG had more significant and quicker improvement in pressures and endurance compared to FUG.

Strategies for Inhibition of Biofilm Formation on Silicone Rubber Voice Prostheses: A Systematic Review.

BACKGROUND: Lifetime elongation of the silicone voice rubber prostheses by inhibition of biofilm formation is a primary objective in voice restoration of laryngectomized patients. This systematic review sought to explore the existing strategies in this direction. MATERIALS: We conducted a systematic search of both in vitro and in vivo literature published in PubMed, Scopus, and Cochrane Central Register of Controlled Trials, until December 31, 2022, for published and unpublished trials assessing the strategies for inhibiting biofilm formation on silicone rubber voice prostheses, and appraised quality assessment with the modified Consolidated Standards of Reporting Trials tool. We analyzed the infection prevention capacity of the included antibacterial and antifungal agents. RESULTS: The qualitative synthesis showed that both surface modification methods and prophylactic treatment of silicone rubber voice prostheses present adequate antibiofilm activity. Of note, the majority of the suggested prosthetic surfaces were not chronically exposed to both human fluids and biofilm-forming microorganisms. CONCLUSION: Various experimental methods provide promising antibiofilm activity and, thus, possible lifespan elongation of silicone rubber voice prostheses.

Νanomaterial-Loaded Polymer Coating Prevents the In Vitro Growth of Candida albicans Biofilms on Silicone Biomaterials.

Early failure of silicone voice prostheses resulting from fungal colonization and biofilm formation poses a major concern in modern ear nose throat surgery. Therefore, developing new infection prevention techniques to prolong those implants' survivorship is crucial. We designed an in vitro laboratory study to include nanomaterial-enhanced polymer coating with a plasma spraying technique against Candida albicans growth to address this issue. The anti-biofilm effects of high- and low-dose Al2O3 nanowire and TiO2 nanoparticle coatings were studied either alone or in conjunction with each other using checkerboard testing. It was demonstrated that both nanomaterials were capable of preventing fungal biofilm formation regardless of the anti-fungal agent concentration (median absorbance for high-dose Al2O3-enhanced polymer coating was 0.176 [IQR = 0.207] versus control absorbance of 0.805 [IQR = 0.381], p = 0.003 [98% biofilm reduction]; median absorbance for high-dose TiO2-enhanced polymer coating was 0.186 [IQR = 0.024] versus control absorbance of 0.766 [IQR = 0.458], p < 0.001 [93% biofilm reduction]). Furthermore, synergy was revealed when the Bliss model was applied. According to the findings of this work, it seems that simultaneous consideration of Al2O3 and TiO2 could further increase the existing antibiofilm potential of these nanomaterials and decrease the likelihood of localized toxicity.

The Role of Primary Repair of the Recurrent Laryngeal Nerve during Thyroid/Parathyroid Surgery in Vocal Outcomes-A Systematic Review.

Recurrent laryngeal nerve (RLN) injury is a well and long-known complication of thyroid and parathyroid surgery that significantly affects the quality of life of patients. Despite the advances in surgical techniques and technology, it still occurs in clinical practice either as temporary paresis or as permanent paralysis of the corresponding vocal cord. The purpose of the current systematic review is to examine the value of intraoperative repair of the RLN in voice restoration. A systematic review of the existing literature was conducted using PubMed, Scopus, Cochrane Library, and Google Scholar databases according to the PRISMA guidelines. The systematic review resulted in 18 studies, which met the inclusion criteria. An improvement in phonatory function and voice quality was observed in all these studies after immediate RLN reconstruction (not always statistically significant). This improvement appears to be comparable to or even higher than that achieved with other methods of repair, and in some cases, the improvement approaches levels found in normal subjects. Intraoperative RLN reconstruction is not widely used in clinical practice, but the evidence so far makes it a viable and safe alternative to traditional techniques with better long-term results, as it prevents the occurrence of atrophy of the vocal cord and should be considered in the operating room if possible.

CO2 laser or dissection tonsillectomy: A systematic review and meta-analysis of clinical outcomes.

OBJECTIVE: Recent evidence has suggested that performing a tonsillectomy with CO2 laser results in favorable intraoperative and postoperative outcomes. This study aimed to compare the clinical outcomes of CO2 and dissection tonsillectomy. METHODS: We conducted a systematic search in PubMed, Scopus, and Cochrane Central Register of Controlled Trials (CENTRAL), until the 1st of September 2021 for completed studies comparing intraoperative and postoperative outcomes of CO2 laser and dissection tonsillectomy. Primary outcomes were operative time, intraoperative blood loss, and postoperative pain. Secondary outcomes included postoperative hemorrhage and tonsillar fossa healing. A random-effects pairwise meta-analysis of both randomized and non-randomized trials was performed. A subgroup analysis considering the randomization of trials was carried out, and sensitivity analyses linked to the quality of included papers or the age of patients were executed. Quality assessment was appraised with the Cochrane risk of bias and ROBINS-I tools for randomized and non-randomized trials, respectively. RESULTS: Eight trials with 632 cases contributed data to this review. For operative time, a significant difference in favor of CO2 laser tonsillectomy was documented (SMD = -1.32; 95% CI = -2.24 to -0.40; p < 0.005). This was also the case for intraoperative blood loss (SMD = -3.94; 95% CI = -5.62 to -2.26; p < 0.00001). For postoperative pain, no significant differences were detected on day one and seven between the intervention groups (SMD = -0.24; 95% CI = -1.11 to 0.63; p = 0.59 and SMD = 1.31; 95% CI = -0.14 to 2.75; p = 0.08, respectively). CO2 laser tonsillectomy was not superior to conventional dissection tonsillectomy regarding postoperative bleeding rates (OR = 0.50; 95% CI = 0.10 to 2.53; p = 0.40). CONCLUSION: This study demonstrates that CO2 laser tonsillectomy is more likely to result in a clinically meaningful decrease in operative time and blood loss compared to the conventional dissection technique in both pediatric and adult patients. We found no significant difference in postoperative pain and bleeding. Performing further level-1 trials on this topic with a standardized and validated outcome measurement method will enable more robust conclusions to be drawn.

A Rare Case of a Fenestrated Retromandibular Vein Lying Lateral to the Facial Nerve Bifurcation.

Facial nerve integrity is the cornerstone of parotid surgery. Although a variety of anatomical landmarks have been employed, facial nerve injury still happens causing devastating functional and cosmetic sequelae. The retromandibular vein is considered one of the most consistent structures lying just deep into the facial nerve. In our cadaveric study, we found a fenestrated retromandibular vein lying superficial to the bifurcation of the facial nerve. This rare anatomical variation would have been a challenge for a hypothetic parotidectomy. Surgeons should be aware of both anterograde and retrograde dissection of the facial nerve and choose the most proper approach to preserve the integrity of the facial nerve.

Platelet-Rich Fibrin in Otorhinolaryngology.

Background: Platelet-rich fibrin is a second-generation platelet concentrate. It is rich in platelets, cytokines, growth factors and leukocytes. Compared to platelet-rich plasma, it releases growth factors for a more extended amount of time. Methods:A literature review was conducted on the applications of platelet-rich fibrin in otolaryngology. Only articles written in English were further considered for the study; all others were excluded. Also, articles relating to oral and maxillofacial surgery were removed. Results: Twenty-five studies were deemed appropriate for inclusion in the present review. Conclusion:Based on the current data, platelet-rich fibrin appears to be a safe, healing-promoting material. It is a cost-effective, autologous material with enormous therapeutic application potential in the future. However, further clinical research is required before conclusive conclusions can be drawn about its usefulness.

Dysphagia Management in Children: Implementation and Perspectives of Flexible Endoscopic Evaluation of Swallowing (FEES).

Dysphagia is any impairment of swallowing that compromises the safety, efficiency, or adequacy of nutritional or liquid intake. It is common in children, especially in some clinical populations, and may result in failure to thrive and respiratory problems due to pulmonary aspiration. Swallowing disorders have a severe impact on children's health, growth, and development, and on the quality of life of the child and family. Clinical evaluation cannot validly predict aspiration, which is mostly silent. A team management approach is advocated, including instrumental swallowing assessments. FEES has been proven to be safe and valid and is increasingly used in children of all ages. It allows the identification of structural abnormalities, assessment of the child's diet with real-life food and liquids while the child holds the optimal or preferred position, examination during breastfeeding, and assessment of fatigue and treatment strategies. FEES is carried out following a protocol that comprises three parts: the evaluation of the anatomical and physiological parameters of swallowing, testing of food and liquids of a range of different consistencies, and evaluation of treatment methods. Pediatric FEES involves adaptations for infants, and special considerations about readiness for nutritive trials and the infant's ability to sustain a coordinated feeding pattern. Varying consistencies and volumes of food or liquids are tried. Care of the dysphagic child involves team work. FEES, as a part of the assessment and management of dysphagia, enables the evaluation of the safety, efficiency, and adequacy of oral food and liquid intake. Future perspectives include standardized training in clinical FEES protocols to ensure clinical competency of the pediatric FESS team members and the development and validation of standardized examination and interpretation protocols for pediatric FEES.

Quality of Life in Oral Cancer Patients in Greek Clinical Practice: A Cohort Study.

Cancer of the oral cavity is one of the most common cancers all over the world. Oral cancer and its treatment impacts on patients' Quality of Life (QOL). The purpose of the present study was to assess oral cancer patients' QOL after the completion of surgical therapy, and to investigate factors affecting it. This was a prospective cohort study, conducted at the Department of Oral & Maxillofacial Surgery, of a large general public hospital in Northern Greece. The sample consisted of 135 consecutive eligible cancer patients. Three distinct questionnaires were used. The first one included questions regarding the participants' demographic characteristics and relevant clinical information. The second comprised the European Organization for Research and Treatment core module (EORTC QLQ-C30) and its head and neck module EORTC QLQ-H&N35. The third was the Functional Assessment of Cancer Therapy-General (FACT-G) assessment of quality of life. We also included the physician-completed Karnofsky scale to assess the functional status of the participants. We found that location of the tumor affects QOL and specifically social contact (H = 17.89, p = 0.001), on the first assessment, and nutritional supplements (H = 22.49, p = 0.000), on the fourth assessment. QOL in patients deteriorates immediately after treatment but significantly improves over time. Health care professionals should take into account these results and arrange care plans in order to find ways to increase patients' QOL.

Smell as a Disease Marker in Multiple Sclerosis.

Existing data suggest that people with multiple sclerosis (pwMS) are at an elevated risk for experiencing olfactory impairment. We investigated if smell dysfunction can be used as an MS disease marker. This is a cross-sectional, case−control study. All data were collected prospectively from 171 participants, 115 pwMS and 56 controls (age and sex stratified and matched to the patients), who reported smell, taste, and nasal breathing, and completed the Greek-validated questionnaires for nasal obstruction (NOSE), nasal-symptoms QoL (SNOT-22), and olfaction-associated QoL (QOD). The smell was assessed with the "Sniffin' sticks" (odor threshold (OT), discrimination (OD), identification (OI) test, and total TDI). We recorded the pwMS disease characteristics (Expanded Disability Status Scale-EDSS, the disease type and duration), cognitive function, emotional status, fatigue, and impact of MS in everyday activities. A TDI < 30.75 (hyposmia) was detected in 30.8% of the patients. The patients' OD and TDI scores were significantly lower than the controls' (p = 0.005, and 0.015, respectively). The hyposmia correlated with disease severity and duration. The EDSS score correlated negatively with OD (r = −0.299, p = 0.001) and TDI (r = −0.242, p = 0.01). The disease duration correlated negatively with OD (r = −0.305, p = 0.001, OI (r = −0.253, p = 0.008) and TDI (r = −0.3, p = 0.001). The information processing speed (SDMT) correlated with OD, OT, and TDI (r = 0.302, p = 0.002; r = 0.242, p = 0.016; r = 0.326, p = 0.001). The olfactory function is changing in MS in accordance with disease progression.

Case report: An unusual case of 'black' larynx.

Ulcerative necrotic supraglottitis is a rare entity of laryngeal infection leading rapidly in laryngeal necrosis, systematic complications and potentially fatal outcomes. We present a case of a 50-year-old gentleman with ulcerative necrotising supraglottitis and no co-morbidities who presented in Ear Nose and Throat Service in the Accident and Emergency department due to dysphagia and weakness. He was treated with an emergency tracheostomy with neck exploration and washout and received appropriate supporting antibiotic regime. He improved and was eventually decannulated, able to breathe phonate and swallow appropriately. After a thorough review of the literature regarding necrotising infections of the laryngeal cavity, only 7 cases have been reported, all in immunocompromised patients with severe complications. Our case report is the first ulcerative necrotic supraglottitis in a healthy individual who was treated early and aggressively with impressive results.

Swallowing disorders after thyroidectomy: a systematic review and meta-analysis.

PURPOSE: Swallowing disorders following thyroidectomy are common, even after surgery without confirmed complications. The purpose of the current systematic review is to investigate the prevalence of dysphagia at various time points after thyroidectomy, at the whole spectrum of it (total/partial, open/endoscopic, for benign/malignant disease). METHODS: The literature available at PubMed, SciELO and Cochrane Library databases was reviewed, according to PRISMA guidelines, using the terms "dysphagia", "swallowing disorder", "deglutition disorder", "thyroidectomy" and "thyroid surgery" in the appropriate combinations. A quantitative synthesis of the results followed. RESULTS: The systematic review of the literature resulted in 35 articles, which met the inclusion criteria and were analyzed regarding their type, sample, follow-up and results regarding post-thyroidectomy dysphagia in multiple follow-up times. A significant increase of swallowing impairment compared to baseline was recorded shortly after surgery. Dysphagia reverted to pre-operative levels 2-3 months later. Dysphagia continued to be reported in a significantly lower proportion of patients, even 1 year after surgery. No significant difference was noticed between open and endoscopic thyroid surgery at 2-3 months post-surgery. CONCLUSIONS: The swallowing disorders reported after thyroidectomy should be expected, but are not always detectable through objective methods. This should not lead to underestimation of symptoms, since the patients' quality of life is negatively affected by the symptomatology.