Cochlear implant cost analysis in adults: a European narrative review.

PURPOSE: The aim of this study was to provide an updated European narrative review spanning the last decade, focusing on the cost-effectiveness of cochlear implants (CIs) for adults with severe to profound post-lingual hearing loss. METHODS: This review encompasses both prospective and retrospective approaches, as well as cross-sectional and longitudinal trials conducted on CIs in adults. All studies related to European countries (Austria, Germany, Switzerland, the Netherlands, Sweden, the UK and Poland) were conducted in English and were published between 2012 and June 2023. RESULTS: Nine studies were included in the analysis. The patients' ages ranged from 18 years to over 67 years, with sample sizes ranging from 20 to 100 patients; two of these studies were focused on single-sided deafness in adults. The Markov model was identified as the most commonly utilized analysis method. CONCLUSIONS: This review identified a general consensus on CI cost-effectiveness, despite substantial variability among countries in factors such as observation time horizons, cost-effectiveness thresholds, methods of cost collection, discount rates, CI eligibility criteria and country-specific health systems. Generally, CIs yield positive societal benefits for working-age individuals, potentially less for seniors. Early unilateral CI enhances cost-effectiveness, highlighting the importance of prompt candidate identification. A consistent undersupply of CIs relative to the percentage of potential recipients emerged across countries. Therefore, further investigation into subcategories such as single-sided deafness is warranted, along with country-specific cost analyses. Emphasizing the significance of detailed information on health systems and associated costs and benefits is crucial for facilitating comparisons across different settings.

Determination of Chloramphenicol in Honey Using Salting-Out Assisted Liquid-Liquid Extraction Coupled with Liquid Chromatography-Tandem Mass Spectrometry and Validation According to 2002/657 European Commission Decision.

Honey is a natural food widely consumed due to its high content in nutrients and bioactive substances. In order to prevent hive infections, xenobiotics such as pesticides and antibiotics are commonly used. Chloramphenicol (CAP) is a broad-spectrum antibiotic used to treat honeybee larvae diseases. However, CAP has toxic and nondose-dependent effects in sensitive subjects; for this reason, its use has been prohibited in food-producing animals, such as the honeybee. In this study, we proposed a rapid, simple, and cheap analytical method, based on salting-out assisted liquid-liquid extraction coupled with UHPLC MS/MS detection for the accurate determination of CAP in honey to be used in routine analyses. The parameters that influence the extraction efficiency have been optimized using an experimental design in order to maximize the recovery of the analyte by reducing the matrix effects. Therefore, the developed method was internally validated according to the 2002/657/EC Decision guidelines and applied to the analysis of 96 honey samples.

A label-free immunoassay for Flavivirus detection by the Reflective Phantom Interface technology.

Flaviviruses are widespread and cause clinically relevant arboviral diseases that impact locally and as imported travel-related infections. Direct detection of viraemia is limited, being typically undetectable at onset of symptoms. Therefore, diagnosis is primarily based on serology, which is complicated by high cross-reactivity across different species. The overlapping geographical distribution of the vectors in areas with a weak healthcare system, the increase of international travel and the similarity of symptoms highlight the need for rapid and reliable multi-parametric diagnostic tests in point-of-care formats. To this end we developed a bi-parametric serological microarray using recombinant NS1 proteins from Tick-borne encephalitis virus and West Nile virus coupled to a low-cost, label-free detection device based on the Reflective Phantom Interface (RPI) principle. Specific sequential detection of antibodies in solution demonstrates the feasibility of the approach for the surveillance and diagnosis of Flaviviruses.

Sudden sensorineural hearing loss: is there a relationship between routine haematological parameters and audiogram shapes?

OBJECTIVE: To investigate the relationship between haematological routine parameters and audiogram shapes in patients affected by sudden sensorineural hearing loss (SSNHL). DESIGN: A retrospective study. All patients were divided into four groups according to the audiometric curve and mean values of haematological parameters (haemoglobin, white blood cell, neutrophils and lymphocytes relative count, platelet count, haematocrit, prothrombin time, activated partial thromboplastin time, fibrinogen and neutrophil-to-lymphocite ratio) of each group were statistically compared. The prognostic role of blood profile and coagulation test was also examined. STUDY SAMPLE: A cohort of 183 SSNHL patients without comorbidities. RESULTS: With a 48.78% of complete hearing recovery, individuals affected by upsloping hearing loss presented a better prognosis instead of flat (18.36%), downsloping (19.23%) and anacusis (2.45%) groups (p = 0.0001). The multivariate analysis of complete blood count values revealed lower mean percentage of lymphocytes (p = 0.041) and higher platelet levels (p = 0.015) in case of downsloping hearing loss; with the exception of fibrinogen (p = 0.041), none of the main haematological parameters studied resulted associated with poorer prognosis. CONCLUSIONS: Our work suggested a lack of association between haematological parameters and a defined audiometric picture in SSNHL patients; furthermore, only fibrinogen seems to influence the prognosis of this disease.

Audiologic profile of OSAS and simple snoring patients: the effect of chronic nocturnal intermittent hypoxia on auditory function.

The objective of this work was to study the effect of nocturnal intermittent hypoxia on auditory function of simple snoring patients and subjects affected by OSAS; we compared the audiologic profile with the severity of OSAS to detect early signs of cochlear damage. One hundred-sixty patients underwent overnight polysomnography, micro-otoscopy, multi-frequency audiometry, acufenometry, TEOAE recording and d-ROMs test. All subjects were divided in four groups, based on presence/absence of AHI (simple snoring without OSAS, mild OSAS, moderate OSAS, severe OSAS). Sixty (37.5 %) patients were not affected by OSAS, 58 (36.25 %) presented a mild OSAS, 18 (11.25 %) a moderate OSAS and 24 (15 %) a severe OSAS; the 57.14 % of moderate to severe OSAS suffered from tinnitus with respect to the 31.03 % of mild OSAS (P = 0.024). A higher percentage (41.66 %) of hearing loss was found among individuals with moderate to severe degree of OSAS (P < 0.0001). All groups were characterized by a mean hearing threshold <25 dB HL for 0.25-3 kHz frequencies and a progressive decrease in hearing sensitivity, particularly for 6-16 kHz frequencies (P < 0.05). The analysis of otoacoustic emissions SNR mean values evidenced a significant difference between simple snoring and severe OSAS individuals for 3 and 4 kHz frequencies (P < 0.05). d-ROM levels resulted higher in patients with severe OSAS with respect to simple snoring subjects (P = 0.004). Our data underline the key role of chronic nocturnal intermittent hypoxia in the development of an early cochlear damage and a more marked high-frequency hearing loss in case of severe OSAS (P < 0.05).

Target screening method for the quantitative determination of 118 pyrrolizidine alkaloids in food supplements, herbal infusions, honey and teas by liquid chromatography coupled to quadrupole orbitrap mass spectrometry.

An analytical procedure for the screening of 118 pyrrolizidine alkaloids (PAs) was successfully validated and applied to their quantitative determination in food supplements, herbal infusions, honey, and teas. It provides the reliable analyte identification by high-resolution tandem mass spectrometry (HRMS/MS), the accurate determination of 21 regulated PAs, and broad contamination profiles. 10% of 281 analyzed samples resulted contaminated at levels above the maximum levels (MLs) of European legislation. The contamination of herbal infusions of mixed plants can represent a possible health concern (23%; mean of PA sum above ML). A high number of PAs not included in the regulation was detected in honey and herbal food supplements, but their contribution was only relevant to the overall level in honey. The results indicate the need to continue collecting contamination data in food supplements and infusions of mixed herbs and to expand the PA-pool to be monitored in honey and related products.

An analytical platform for the screening and identification of pyrrolizidine alkaloids in food matrices with high risk of contamination.

An analytical platform for the detection of pyrrolizidine alkaloids (PAs) in honey, pollen, teas, herbal infusions, and dietary supplements is proposed; it includes a wide-scope suspect screening method, based on a diagnostic product ion filtering strategy for the characterization of PAs, and a target screening and identification method for the high-throughput detection of 118 PAs of a high-resolution mass spectral library. Salting-out assisted liquid-liquid extraction of aqueous extracts combined to ultra-high performance liquid chromatography-high-resolution tandem mass spectrometry was employed. The limit of identification (0.6-30 µg kg-1) of 28 standards were fit-for-purpose in PA-monitoring applications, with a false negative rate <1.3 % at 4 µg L-1. The wide-scope suspect screening method allowed the tentative identification of 88 compounds. The screening of 282 commercial samples revealed a broad contamination of the studied matrices, demonstrating the effectiveness of the platform in detecting and identifying both target and untarget PAs.

A multi-analyte screening method for the rapid detection of illicit adulterants in dietary supplements using a portable SERS analyzer.

The popularity and number of dietary supplements on the health market have experienced an unprecedented boost in recent years. Simultaneously, their increased use has been accompanied by an increase in acute intoxication cases linked to the adulteration of these products with illicit and undeclared substances. In this study, a SERS-based screening methodology was developed to rapidly detect illegally added pharmaceutically active substances to dietary supplements. A portable analyzer and silver printed-SERS substrates were used to enhance the signal, requiring less than 20 min of sample preparation prior to the analysis. The method was successful in the qualitative identification of eleven out of twenty-three illicit adulterants in the dietary supplements; it could detect the target compounds at realistic adulteration levels (0.1-5.0% w/w), demonstrating the potential of SERS-based methodologies for forensic rapid screening applications. The developed method is quick, easy to use, requires no skilled technicians and little sample preparation, and allows in-situ analyses. For these reasons, it is suitable for quick screening to be performed by inspectors at customs. Moreover, the low specificity of spectroscopic methods, to which SERS belongs, would benefit the detection of newly synthesized analogues of the target adulterants, which would otherwise be more difficult using common mass spectrometry methods in absence of reference standards.

Otological Planning Software-OTOPLAN: A Narrative Literature Review.

The cochlear implant (CI) is a widely accepted option in patients with severe to profound hearing loss receiving limited benefit from traditional hearing aids. CI surgery uses a default setting for frequency allocation aiming to reproduce tonotopicity, thus mimicking the normal cochlea. One emerging instrument that may substantially help the surgeon before, during, and after the surgery is a surgical planning software product developed in collaboration by CASCINATION AG (Bern, Switzerland) and MED-EL (Innsbruck Austria). The aim of this narrative review is to present an overview of the main features of this otological planning software, called OTOPLAN®. The literature was searched on the PubMed and Web of Science databases. The search terms used were "OTOPLAN", "cochlear planning software" "three-dimensional imaging", "3D segmentation", and "cochlear implant" combined into different queries. This strategy yielded 52 publications, and a total of 31 studies were included. The review of the literature revealed that OTOPLAN is a useful tool for otologists and audiologists as it improves preoperative surgical planning both in adults and in children, guides the intraoperative procedure and allows postoperative evaluation of the CI.

COVID-19 and Deafness: Impact of Face Masks on Speech Perception.

BACKGROUND: The COVID-19 pandemic has made wearing face masks a common habit in public places. Several reports have underlined the increased difficulties encountered by deaf people in speech comprehension, resulting in a higher risk of social isolation and psychological distress. PURPOSE: To address the detrimental effect of different types of face masks on speech perception, according to the listener hearing level and background noise. RESEARCH DESIGN: Quasi-experimental cross-sectional study. STUDY SAMPLE: Thirty patients were assessed: 16 with normal hearing [NH], and 14 hearing-impaired [HI] with moderate hearing loss. DATA COLLECTION AND ANALYSIS: A speech perception test (TAUV) was administered by an operator trained to speak at 65 dB, without a face mask, with a surgical mask, and with a KN95/FFP2 face mask, in a quiet and in a noisy environment (cocktail party noise, 55 dB). The Hearing Handicap Index for Adults (HHI-A) was administered twice, asking subjects to complete it for the period before and after the pandemic outburst. A 2-way repeated-measure analysis of variance was performed. RESULTS: The NH group showed a significant difference between the no-mask and the KN95/FFP2-mask condition in noise (p = 0.01). The HI group showed significant differences for surgical or KN95/FFP2 mask compared with no-mask, and for KN95/FFP2 compared with surgical mask, in quiet and in noise (p < 0.001). An increase in HHI-A scores was recorded for the HI patients (p < 0.001). CONCLUSION: Face masks have a detrimental effect on speech perception especially for HI patients, potentially worsening their hearing-related quality of life.

Effectiveness of Rehabilitative Intervention on Pain, Postural Balance, and Quality of Life in Women with Multiple Vertebral Fragility Fractures: A Prospective Cohort Study.

Patients with vertebral fragility fractures often experience chronic pain, postural and balance disorders, and poor quality of life (QoL). Although several studies have investigated the role of rehabilitation in severe osteoporosis, the effectiveness of this intervention in patients with multiple vertebral fractures is poorly known. The aim of our longitudinal cohort study is to evaluate the effectiveness of rehabilitation, including postural training, resistance exercises, and visual stabilization exercises, for a 7-week period, on the pain, postural balance, and QoL of subjects with at least two vertebral fragility fractures receiving denosumab and vitamin D. We investigated, before (T0) and after (T1, at 7 weeks) rehabilitation, the following outcome measures on 28 patients: pain (Numerical Rating Scale (NRS)), self-perceived QoL (36-Item Short Form Survey (SF-36) and Mini-Osteoporosis Quality of Life Questionnaire (Mini-OQOL)), dizziness (Dizziness Handicap Inventory (DHI-I)), mobility (Timed-Up and Go (TUG) test), and instrumental posturographic assessment (FreeMed posturography system). At the end of the treatment, improvements of pain and QoL were recorded. Pain relief was highly obtained in patients with more than two vertebral fractures. Moreover, a significant functional improvement (TUG test) was found in those with two vertebral fractures, without any statistically significant change reported for other outcomes. Our findings suggest that combined intervention, including anti-osteoporotic drugs and postural rehabilitation, should be proposed to osteoporotic patients with multiple vertebral fractures.

Determination of mycotoxins in beer by multi heart-cutting two-dimensional liquid chromatography tandem mass spectrometry method.

Beer is one the most consumed alcoholic beverage in the world and its contamination with mycotoxins is of public health concern. This study reports a fast and automated analytical procedure based on a multi-heart-cutting two-dimensional liquid chromatography tandem mass spectrometry method using electrospray ionization for the determination of seven mycotoxins (aflatoxins B1, B2, G2 and G1, ochratoxin A, fumonisins B1 and B2) in beers. The developed method was based on the heart-cutting 2D- HPLC technique in which only the specific portions of the first dimension, in the retention time of analytes, were transferred into the second dimension for the further separation and successive determination. The method uses two different chromatographic columns; in the first dimension, 50 µL of sample was injected on first column, and mycotoxins elution regions were collected in a loop and transferred into the second column for the separation of analytes. Each column operated in gradient elution mode in order to eliminate interfering compounds and improve separation and peak shape. After the optimization, the method has been validated according to EU regulation and finally applied for the analysis of forty beer samples collected from Italian supermarkets. Among all mycotoxins studied, fumonisins B1 was the most widely distributed in analysed beers (>21%) in the range from 0.6 to 12.3 ng mL-1. The automated methodology developed was able to determine accurately and simultaneously seven mycotoxins in beer. This provided a significant reduction of sample handle and, consequently of analysis time.

Orofacial muscles activity in children with swallowing dysfunction and removable functional appliances.

Swallowing dysfunction is a frequent disorder among children and refers to an altered tongue posture and abnormal tongue movement during swallowing. Removable functional appliance is one of the treatments applied by dentistry to correct this disorder. The aim of this study was to evaluate any differences on orofacial muscles activity in children with swallowing dysfunction with and without removable functional appliances. 68 children were eligible for the study and divided into the orthodontic group (OG) and the no-orthodontic group (NO-OG). Both groups performed a dental occlusion-class evaluation, a swallowing function test and a myoscan analysis in order to measure perioral forces (i.e. tongue extension force, lip pressure, masseter contraction force). Our results showed a significant difference (P=0.02) between OG and NO-OG for the tongue extension force, whereas no significant differences (P>0.05) were found for the other parameters. Our findings suggest that children with swallowing dysfunction and removable functional appliance show orofacial muscles activity within the range of reference values (except for the lip pressure). However, we hypothesize that orthodontic treatment can achieve more effective results with integration of myofunctional therapy.

Phage Display Technology for Human Monoclonal Antibodies.

During the last 20 years in vitro technologies opened powerful routes to combine the generation of large libraries together with fast selection and screening procedures to identify lead candidates. One of the most successful methods is based on the use of filamentous phages. Functional Antibodies (Abs) fragments can be displayed on the surface of phages by fusing the coding sequence of the antibody variable (V) regions to the phage minor coat protein pIII. By creating large libraries, antibodies with affinities comparable to those obtained using traditional hybridoma technology can be isolated by a series of cycles of selection on the antigen of interest. In this system, antibody genes can be recovered simultaneously with selection and can be easily further engineered, for example by increasing their affinity to levels unobtainable in the immune system, or by modulating their specificity and their effector functions (by recloning into a full-length immunoglobulin scaffold). This chapter describes the basic protocols for antibody library construction and selection of binder with desired specificity.

HMGA1 regulates the Plasminogen activation system in the secretome of breast cancer cells.

Cancer cells secrete proteins that modify the extracellular environment acting as autocrine and paracrine stimulatory factors and have a relevant role in cancer progression. The HMGA1 oncofetal protein has a prominent role in controlling the expression of an articulated set of genes involved in various aspect of cancer cell transformation. However, little is known about its role in influencing the secretome of cancer cells. Performing an iTRAQ LC-MS/MS screening for the identification of secreted proteins, in an inducible model of HMGA1 silencing in breast cancer cells, we found that HMGA1 has a profound impact on cancer cell secretome. We demonstrated that the pool of HMGA1-linked secreted proteins has pro-migratory and pro-invasive stimulatory roles. From an inspection of the HMGA1-dependent secreted factors it turned out that HMGA1 influences the presence in the extra cellular milieu of key components of the Plasminogen activation system (PLAU, SERPINE1, and PLAUR) that has a prominent role in promoting metastasis, and that HMGA1 has a direct role in regulating the transcription of two of them, i.e. PLAU and SERPINE1. The ability of HMGA1 to regulate the plasminogen activator system may constitute an important mechanism by which HMGA1 promotes cancer progression.