Due to a lack of knowledge about age-related hearing loss, its early identification and appropriate intervention are not being carried out in the field of dementia care. Since the untreated hearing loss of the elderly leads to a more rapid cognitive decline, the present study aimed to understand the hearing-related knowledge, attitudes, and practices of healthcare professionals in long-term care (LTC) facilities in Korea. A total of 557 workers  in residential LTC participated in this cross-sectional multicenter survey study. The Korean version of the knowledge, attitudes, and practice (KAP) on-line survey with a five-point scale or yes/no response was applied as the experimental tool. The results of structural equation modeling showed that knowledge significantly affected the attitudes and health-seeking practices of the facility manager, and allied healthcare professionals demonstrated similar results, which showed the significant effects of that knowledge on attitudes and health-seeking practices. This clearly indicated that sufficient knowledge is the driving force for the health-seeking practices and positive attitudes of both the facility manager and the healthcare professionals. Thus, we suggest that a further step, such as the development of comprehensive and professional guidelines regarding hearing care information for these professionals in residential LTC facilities, should be followed, and believe that this effort could lead to improving hearing-related knowledge, attitudes, and practices in order to clinically and politically care for the elderly population. Without a doubt, aging is the biggest risk factor for sensory impairments, which include hearing loss and dementia ,2,3,4. AAlthough contemporary researchers have indicated that timeliness and appropriate methods for the intervention of hearing loss could alleviate the related symptoms for patients with dementia , most caOn the other hand, the knowledge, attitudes, and practices (KAP) model highlights the relation between the main components of knowledge (known), attitudes (believed), and practices (carried out) . From thAlthough this international cross-sectional study had advantages in terms of a comparison between nations with the same notion, there were several inevitable limitations, i.e., an unbalanced sample population . In a siA study design of a cross-sectional multicenter survey was adapted to investigate self-reported knowledge, attitudes, and practices of the healthcare professionals toward older adults with hearing loss. These healthcare professionals included clinicians, nurses, social welfare workers, care workers , and other allied healthcare professionals in the long-term care (LTC) facilities of South Korea. According to the Ministry of Health and Welfare and National Medical Center, there was a total of 286 LTC centers with approximately 3153 workers as of October 2020 . In detaTo consider the equal distribution of participants and minimize any location bias, all the 286 LTC centers were selected and asked to enroll in the present study. The data collection was conducted between December 2020 and August 2021. Of the 3153 workers in these 286 LTC centers, 557 workers  participated in the on-line survey. The demographic information for these 557 workers is presented in All procedures of the current study were approved by the Institutional Review Board of Hallym University  and all experiments were conducted in compliance with the Declaration of Helsinki, International Conference of Harmonization Guidelines for Good Clinical Practice. Before conducting any experiment, the participants had to agree to the consent form.Based on the knowledge, attitudes, and practice (KAP) theory, which is a theoretical model for human health behavior (homogeneous concept with practice), practice is affected by knowledge and attitudes of oneself . To consIn order to classify the items between facility manager and healthcare professionals, “M”, which stands for facility manager, was attached in front of the item number . In the same way, “H”  was positioned in front of the item number in the healthcare professionals’ version.For facility managers, in detail, the knowledge area asked questions such as the number and degree of hearing loss patients (MK1); knowledge and management of hearing test tools, including a screening test tool, questionnaire, and equipment (MK2); how hearing loss patients were referred to a clinician (MK3); and any audiological support in terms of facility management (MK4). All responses except for the practice area (yes or no choices or asking an open question to describe their thoughts) were quantified on a 5-point Likert scale (1: strongly disagree to 5: strongly agree). The mean score of the knowledge area was 1.12 (SD: 1.18) with a 0.76 reliability as measured by Cronbach’s alpha coefficient. The attitudes area was designated to measure the willingness and feasibility of their attitudes. These items included: the feasibility of a hearing test as a simple screening for their patients (MA1), willingness to seek clinical guidelines (MA2), necessity of having a routine hearing test (MA3), relationship between hearing loss and dementia (MA4), and necessity of having a hearing and cognitive test (MA5). The reliability of attitudes aspect was relatively high . With purpose of identifying the presence of the actual practice themselves, the practice area  included the following items: possibility (MP1) and feasibility of a hearing test (MP2), presence of clinical guidelines (MP3), specialists in hearing (MP4), education and support of hearing-assistive devices (MP5), hearing loss (MP6), and communication strategy (MP7), communication with patients (MP8) and communication with family members (MP9), providing support information for patients (MP10), and usefulness of information received from a hearing specialist (MP11).The knowledge area  of healthcare professionals included an awareness of hearing loss patients (HK1) and hearing tests (HK2), expertise in the interpretation of hearing test results (HK3), a referral process for hearing loss patients (HK4), request for audiological support (HK5), and confidence of care of dementia patients with hearing loss (HK6). The unlikely knowledge area and attitudes area consisted of 3 items: the feasibility of a hearing test in both simple testing and screening for their patients (HA1), intention to seek clinical guidelines (HA2), and the effectiveness of hearing aids in patients (HA3). The mean score and reliability of attitudes areas were 2.12 (SD: 0.85) and 0.67, respectively. The practice area  intended to measure the actual practice of patients in their facility, for example, whether they conducted hearing aids management (HP1) or not, the presence of a hearing specialist (HP2), and the education history of hearing aids management (HP3).p > 0.05), root mean square error of approximation (RMSEA), and goodness-of-fit index (GFI)), incremental fit , comparative fit index (CFI), and normed fit index (NFI)), and parsimonious fit ) were used. The statistical analysis process was conducted using the two-step approach, while indicating the validation of the pooled measurement model using a confirmatory factor analysis (CFA) as the first step and confirmation of the relationship between the variables in the structural model using path analysis as the second step [All variables were pre-processed for statistical analysis using R statistical computing software . The strond step .The information from the facility where the respondents to the present study were working is presented in the form of job-specific questions for the facility manager in Additionally, some open questions were provided for both the facility manager and healthcare professionals to identify the specific reasons for their responses. In the knowledge area, the healthcare professionals were asked why they were not confident in treating patients with hearing loss who required hearing aids. The major reason for this was a lack of education on the use and/or maintenance (20.53%). The other reasons were a lack of education in checking and/or cleaning hearing aids (17.22%), turning hearing aids on/off (10.60%), checking to see whether hearing aids were working or not (4.42%), and changing the batteries of a hearing aid (1.32%). The healthcare professionals were also asked about attitudes, such as the reason why the patients did not use a hearing aid effectively. The reasons healthcare professionals gave were that the hearing aid was too expensive (28.70%), not appropriately fitted (13.02%), hard to use and not tolerated (11.26%), lost or broken (3.09%), and ineffective (1.99%). For health-seeking practices, the facility managers were asked to respond regarding the specific methods used to conduct the hearing (screening) test, the name of the test materials , the detailed role of designated workers who were responsible for hearing care, the detailed content of hearing education or communication strategies, and methods to help or communicate to patients with dementia and hearing loss. The facility managers responded that the reports of patients and family members were the most frequently used methods for hearing (screening) tests. They usually used a voice amplifier as the test and/or communication tools with patients. The alternatives included hearing aid counseling, referral to hospital, speechreading, and writing. Meanwhile, the healthcare professionals also responded regarding health-seeking practices, such as the testing or checking method in their practices. They conducted their practices based on the reports of patients (36.42%), checking whether the hearing aid was working or not (33.33%), and reports from family members (30.25%).p-value of chi-square < 0.001, 0.064 of RMSEA, 0.824 of GFI, 0.778 of AGFI, and 0.567 of NFI (see p < 0.001) and 0.889 of the NFI value. To consider the modification indices for factor loadings, several modifications of the model were conducted, and the final model was thus derived.The results of the goodness-of-fit measurement for the basic model of facility manager revealed that it had several weak points in goodness-of-fit index, such as the  NFI see . In the 2(24) = 119.36, p < 0.001). In addition, comparative results of the model indices between the basic and final model of healthcare professionals demonstrated that the final model had a greater statistically significant improvement than the basic model (χ2(24) = 151.68, p < 0.001). The results of the goodness-of-fit measurement for both the basic and final models for both groups are shown in Based on the results of the basic model of a facility manager, the covariant relations were established and corrected. After a repeated adjustment and model fitting, the final KAP model of the facility manager showed better fit indices than the basic model (χp < 0.05) and health-seeking practices . However, the direct effect of attitudes on health-seeking practices was not significant . Similar to the results of facility manager, the path analysis of healthcare professionals demonstrated that significantly direct effects of knowledge were found (p < 0.001) and health-seeking practices . Yet, unexpectedly, the direct effect of attitudes on health-seeking practices was not significant . These results suggested that when both the facility manager and healthcare professionals expanded their knowledge, their attitudes positively affected and, consequently, led to better health-seeking practices and/or behavioral intentions to deliver those practices.The structural model of the facility manager is depicted in re found B. In othThe current study analyzed the associations between knowledge, attitudes, and the practices of allied healthcare professionals in the LTC facility on hearing loss who worked for the elderly with dementia using the SEM technique.The results from this current cross-sectional multicenter study suggested that both the facility manager and healthcare professionals had a limited and low level of hearing-related knowledge and attitudes toward their patients with dementia. As expected, these results were consistent with the cross-sectional multinational survey study of Dawes et al. . They reThe statistical analysis using an SEM technique in the current study revealed that knowledge is the driving force of health-seeking practices and attitudes for both the facility manager and healthcare professionals. Additionally, the results of facility managers demonstrated that hearing-related knowledge was more strongly associated with health-seeking practices than the attitudes toward their patients. However, the pattern of KAP model-based outcome measures differed amongst healthcare professionals. That is, greater knowledge of healthcare professionals was more strongly linked with attitudes of their patients than health-seeking practices.The descriptive data of our study showed that facility managers strongly agreed to all survey items related to attitudes . However, the results for the same variable for healthcare professionals differed from the facility manager. For example, healthcare professionals negatively responded to the questions related to hearing aids (30.24% of respondents replied that they strongly disagreed and 19.65% strongly agreed). Thus, hearing-related knowledge and attitudes were limited for various reasons , resulting in a strong association between the knowledge and attitudes of healthcare professionals. These results were supported by several studies with different academic fields ,36. In oThis study has several limitations. One of the limitations is the limited variables for mediating effects in the KAP model. A poor communication ability in the patients with concurrent hearing loss and dementia was one of the main obstacles in clinical practice and a burden for allied healthcare professionals . Mamo anThe other limitation was the lack of specific items on the survey instrument. Although the K-KAP survey used in the current study was derived from a part of the SENSE-Cog Program ,37, whicThe findings of the current study allowed us to explore the association between the main factors of the KAP model, analyzing them using sophisticated statistical methods and the SEM technique for allied healthcare professionals who care for and manage the elderly with dementia and hearing loss. First, the results showed that both the facility manager and healthcare professionals had a limited and low level of hearing-related knowledge and attitudes toward their patients with dementia. Secondly, the knowledge component was the driving force behind the attitudes and health-seeking practices of both the facility manager and healthcare professionals. However, the pattern of path analysis was different from the facility manager and healthcare professionals. The knowledge of the facility manager more positively impacted health-seeking practices rather than attitudes. On the other hand, knowledge towards attitudes was more positively and strongly affected in case of healthcare professionals. Based on the results of the study, we conclude that a comprehensive and professional hearing care guideline should be developed to improve hearing-related knowledge, change pessimistic attitudes, and motivate active practices as a positive further step.


Aims: check the feasibility of using self-assessment questionnaires and compare the results achieved by hearing aid fitting in users from a federal public institution, with and without complaints related to hearing amplification characteristics. Materials and Methods: 25 individuals, from 13 to 77 years of age, users of hearing aids. The HHIE-S/HHIA (Hearing Handicap Inventory for the Elderly Screening Version or for Adult) and APHAB (Abbreviated Profile of Hearing Aid Benefit) self-assessment questionnaires used with individuals without (Group 1) and with complaints related to amplification characteristics (Group 2). Results: we did not find significant differences between the HHIE-S/HHIA and APHAB groups; except in APHAB’s ease of communication item, where Group 1 seemed to benefit more. Moreover, we noticed a significant reduction in hearing disability with the use of hearing aids in favorable communication situations, noisy environments for both groups. Conclusion: these questionnaires proved to be valuable for predicting the difficulties faced by the users, and significant differences were found in favorable communication situations, where the group without complaints had the most benefit.An efficient rehabilitation must be able to reduce impairment effects over the auditory and communication skills of individuals and promote psychosocial well being.  Hearing aid selection and fitting process, as well as their effective use, are fundamental in order to start hearing rehabilitation. In order to be considered efficient, it must be able to reduce the effects this disability brings over the auditory and communicative skills of the individual, in other words, his/her auditory disabilities and enhance their psychosocial well-being, thus reducing the disadvantages brought about by the disability or the auditory incapacity, called auditory handicap, a world wide used term by researchers, also used in this study. Moreover, these functional improvements must remain throughout timeIn order to assess intervention results, the literature describes both objective procedures involving in situ measures, functional gains and formal speech recognition tasks, as subjective ones, which may concurrently show speech recognition and other aspects of life, such as difficulties in communication in daily activities. Thus, it is possible to check if the intervention process has reduced these disabilities or the auditory handicap, as well as check patient acceptance and satisfaction with the hearing aidIn order to investigate the individual’s performance or his perception of changes that may occur along time, favorable or not in hearing itself or in social or emotional relationships, the use of tools such as interviews and questionnaires are of the uttermost importance, because by using self-assessment questionnaires of disabilities or of auditory handicap, we obtain subjective measures based on the user’s judgment or his own perceptionAs referred to in the first part of this study, although many investigations have been carried out with hearing aid users, very few of them are attributed to users fit through the Public Health Care system. Therefore, the second part of this investigation aimed at:1.Check the feasibility of using self-assessment questionnaires in patients from a public institution;2.Compare hearing aid use results in users with and without complains related to the amplification characteristics.This study was approved by the Ethics Committee of the Project Cabinet of the Health Sciences Center - CCS - UFSM, protocol # 112/2004. All participants signed the Informed Consent form in order to participate.As it was described in the previous study, we interviewed 31 individuals fitted with hearing aids in the Hearing Aid Laboratory of the Federal University of Santa Maria, through the partnership signed between the State Health Secretariat of Rio Grande do Sul State and the Federal University of Santa Maria, in order to establish a joint action to provide hearing aid for the hearing handicap users of the Public Health Care System-SUS, under protocol 051/2000 signed in 12/29/2000 and published in the Federal Gazette on 02/08/2001, based on Ordinance 432 from the Ministry of Health.After the interview, we started to assess the intervention results by means of subjective measures, that is, self-assessment questionnaires, which help us check the difficulties experienced in daily communication activities.We excluded the cases in which the hearing aids were returned (2) and/or who had associated pathologies (4), which could interfere in evaluating the results.The study group was made up of 25 users, 13 females and 12 males, with ages varying between 13 and 77 years, all of them with symmetric mixed bilateral or sensorineural hearing loss of moderate to severe levels, bilaterally fit with digital or computer-assisted programmable analogical hearing aids.In order to assess communication difficulties and the social and emotional consequences of hearing disability in these users, we used the age-dependent Auditory Handicap self-assessment questionnaires for the elderly in the post-fitting period: Hearing Handicap Inventory for the Elderly Screening Version - HHIE-S (Annex 1), abridged version, developed in 19824 and adapted for the Portuguese Language in 1997Both the HHIE-S and the HHIA are questionnaires made up by two scales: one Social /Situational and the other one is emotional. The first aims at identifying the impact hearing loss would have on the activities performed by the individual, while the second one assesses the behavior and the emotional response to the hearing deficit.HHIE-S is an abridged version of HHIE4, being faster and of easier understanding to be used in the elderly with hearing disability, made up of 10 questions broken down in five items for each scale. Now, the HHIA was developed from the HHIE to be used in hearing impaired patients with ages below 65 years, made up of 25 items, and 12 of them correspond to the Social/Institutional scale; and the other 13 are related to the emotional one. All the individuals below 65 years responded to the protocol adapted to the Brazilian Portuguese Language HHIA not excluding teenagers and young adults, because these are the only equivalent protocols to be used in different populations according to age range.HHIA indices are identical to those from the HHIE-S. All the users were required to answer “yes” (4 points), “sometimes” (2 points) or “not” (no point) for each question. The answers obtained from patients with hearing aids were analyzed and the scores found by scale and total were standardized, in other words, turned into percentage indices, indicating its performance for this situation. The score value could vary between 0 and 100%, and the higher the score obtained; the higher was the patient’s self-perception of the handicap, 18 to 42% indicated little to moderate perception; and above 42%, indicated severe or significant perception.ATTACHMENT IAbridged Version of the Auditory Handicap Questionnaire for the ElderlyINSTRUCTIONS: The following questionnaire has 10 questions. You should chose only one answer for each question, marking an (x) in the proper place. Some questions are similar to others, but they actually have subtle differences, which allow us to better assess the answers. There is no right or wrong answer. You should mark the one you believe to be more adequate in your case or situation.Thank you for your participation!In a second phase, in order to assess hearing aid benefit, we used the Abbreviated Profile of Hearing aid Benefit - APHAB7 (Annex 3) adapted to the Portuguese Language in 1997APHAB is a self-assessment questionnaire, useful to quantify the disability associated with the hearing loss and its reduction with the use of sound amplification. It is based on 24 items, distributed in four subscales, namely: Ease of communication (EC), Reverberation (RV) and Environmental Noise (EN), made to assess speech understanding in different situations of our daily lives, and also Sound Aversion (SA), which quantifies the negative reactions to environmental sounds. For each item we offered two answer options, one “without hearing aids” and another “with hearing aids”, through which we could assess both the individual’s own performance with and without the hearing aid with the benefit supplied by amplification, factoring in the difference between these two indices.Users were instructed to answer the same item in each subscale, for both options “with” and “without” hearing aids, selecting the answer within a continuous seven points scale , which should indicate how frequent each statement was true. Each answer option was associated with a descriptive term and to a percentage, which are: A “always” (99%), B “almost always” (87%), C “usually” (75%), D “half of the time” (50%), and “sometimes” (25%), F “rarely” (12%) and G “never” (1%).The response from each individual for each of the subscales was analyzed and calculated by means of a computer program “Phonak Fitting Guideline 8.5”, indicating its performance for each situation “without” and “with” hearing loss and its benefit, calculating the differences between responses for each situation.In order to analyze the results attained, considering each subscale individually, it is necessary that we have a minimum difference of 22% between the indices with and without hearing aid in at least one of the subscales to represent a real difference between the two situations. Now, if the goal is to have a global evaluation of amplification, a hearing aid index of 10% better than that without hearing aid in three subscales: FC, RV, and RA, really represents an improvement in the individual’s performanceThe first questions in the questionnaire were asked by the examiner and the following, whenever possible, were answered by the individual being studied. In those users in whom we noticed some type of difficulty, either understanding or expressing written language, the examiner asked all the questions verbally.We separated the individuals assessed in two groups based on the qualitative results related with the amplification previously investigated, as follows:Group 1 (G1)Without complaints related to the amplification characteristics (N=8).Group 2 (G2)With complaints related with amplification characteristics (N=15).ATTACHMENT IIQuestionnaire for the Assessment of Auditory Handicap in AdultsINSTRUCTIONS: The following questionnaire has 25 questions. You should pick only one answer for each question, by placing an (x) in the one you find more adequate. Some questions are similar to others, but they actually bear subtle differences that allow us to better evaluate the answers. There is no right or wrong answer. You should mark the one you think is the most adequate to your case or situation.Thank you for participating!ATTACHMENT IIIAssessment Protocol of the Hearing Aid BenefitINSTRUCTIONS: Please, circle the answers that get closer to your day-to-day. Notice that each choice you make includes a percentage. You can use this to decide upon your answers. For example, if one item is true for about 75% of the times, circle letter C. If you have not experienced the situation described, try to thing of a similar situation. If you have no idea, leave it without answering. If you have not experienced the situation described, try to think of a similar situation. If you are still clueless, leave it without answering. A Always (99%) B Almost always (87%) C Usually (75%) D Half of he times (50%) E Sometimes (25%) F Rarely (12%) G Never (1%).Afterwards, the results were statistically analyzed, by using a non-parametric test, which was the Krukal-Wallis test to analyze the statistically significant differences between the situations with and without hearing aids in the APHAB questionnaire and between the two groups by means of HHIE-S, HHIA and APHAB. The level of rejection towards the null hypothesis was fixed in a value equal to or less than 5%. Statistically significant results were marked with an asterisk (*).1. Handicap Inventory for the Elderly Screening Version - HHIE-S or Hearing Handicap Inventory for Adult - HHIA Results obtained for Groups 1 and 2.On 2. Abbreviated Profile of Hearing Aid Benefit - APHAB results obtained for Groups 1 and 2.1. Comments on the results from the Handicap Inventory for the Elderly Screening Version - HHIE-S or Hearing Handicap Inventory for Adult - HHIA obtained for Groups 1 and 2.We noticed a 34.75% of average percentage total scale index for Group 1, with a variation range between 4% and 54%. In the social/situational scale we found an average index of 17.50% and in the emotional scale it was of 17.25%. For Group 2, there was an average index for the total scale of 45.82%, varying between 20% and 95%, and from the total, 24.18% corresponded to the social /situational scale and 21.65%, to the emotional .Statistically significant differences for the social/situational scale, emotional and total between the groups were not found when compared to the indices of auditory handicap perception. Nonetheless, we see better results in the social/situational, emotional and total scales for those patients in Group 1 when compared to Group 2, in other words, there is less auditory handicap perception in the group which did not present complaints related to amplification characteristics . With thOf the 8 users who made up Group 1 in this study, 1 (12.5%) did not show any self-perception of an auditory handicap with scores below 16%; 4 (50%) had self-perception of mild to moderate handicap corresponding to an interval of 18 to 42%; and 3 (37.50%) showed a significant self-perception of the handicap imposed by the auditory deficiency and/or disability, with indices above 42% . MeanwhiMany investigations were carried out in the post fitting period, with the goal of checking the benefit in the long run, of which results from the handicap self-perception found throughout the three years of sound amplification use are similar to those found in the present study, in other words, a mild to moderate perception of the auditory handicap.14According to the aforementioned studies, we notice that the benefit and the satisfaction obtained from sound amplification after a short time interval can show a marked reduction in auditory handicap thanks to the excitement and high user’s expectation, however, a real improvement in performance, able to assess amplification limitations must be obtained after at least 3 months of use, which should remain and stabilize with time.Thus, patient follow up could in fact show treatment efficacy and also check if the amplification would continue being considered beneficial or not1. Thus, these tools, among their many utilities, can be considered useful to check communication problems and/or the psychosocial consequences of hearing loss which remain, even with sound amplification, helping patients through the fitting process, which does not end after checking results, it lasts through time.2. Comments on the results of the Abbreviated Profile of Hearing Aid Benefit - APHAB obtained for Groups 1 and 2.On Therefore, statistically significant differences among he results obtained with and without hearing aids for subscales FC, RV and RA were found for both groups  and 3, aSuch results can be expected, having seen that hearing aids aid in verbal communications under favorable conditions and even in not very pleasant communication situations; nonetheless, with high levels or just a mild worsening in subscale AS with hearing aids can be justified by the fact that the acoustic signals become more intense with sound amplification, thus causing negative reactions to environmental sound. Similar findings to these ones were encountered in many studiesThe benefit reflected by the use of sound amplification was calculated by the differences between the APHAB questionnaire response for both situations, namely: with and without the hearing aid. Positive benefit values mean that a better performance was seen with hearing aid when compared to those without hearing aid. Conversely, negative values show a perception of a worse performance with hearing aid when compared to without hearing aid.For Group 1, we found benefit values of 68.62% (FC), 48.38% (RA), 37.12% (RV) and -9.25% (AS) and in Group 2, we noticed indices of 39.59% (FC), 39.88% (RA), 38.12% (RV) and -28.18% (AS), thus showing a significant reduction in hearing loss with the use of hearing aids in favorable communication situations (FC), in reverberating environments (RV) and in the presence of environmental noise (RA) for both groups. As previously stated, in negative perception situations, performance with the hearing aid was worse for both groups, confirmed by negative benefit indices in Subscale AS .By analyzing the results we noticed statistically significant differences between Groups 1 and 2 only in subscale FC, and Group 1 showed the best results. Nonetheless, in non-favorable verbal communications, we had better benefit results in subscale RV for Group 1 when compared with Group 2, and similar results between both groups in subscale RA .In subscale AS we did not find statistically significant differences between average indexes from Groups 1 and 2, nonetheless, it is stressed that Group 1 was the one who had the lowest results, suggesting that the complaints related to the amplification characteristics presented by Group 2 influenced the performance with hearing aids in high intensity environmental sound, because many of the complaints were related to the high intensity of environmental sounds - headaches and discomfort towards sounds.Different research projectsDespite all of this, as we compared benefit results by scale in this study with those from other studies which assessed experienced users, we found for both groups 1 and 2 similar results as far as benefit is concerned equal to 35%7and 41.42%We found negative results in the aforementioned studies as far as the sound aversion scale is concerned, representing the worst results found in this study when compared to those from Group 1, and when compared to Group 2 they are similar to -30%7 and greater than -18.11%We recommend that the indices of subscale AS be the lowest possible, that is, closer to zero, indicating that the sound amplified by the hearing aids should not be uncomfortably loud, because we believe that this subscale can provide information about adapting the maximum output of these hearing aids, although new investigations are necessary to use it in a proper and precise way.As we perform an individual analysis of the benefit’s results, we observed a difference higher than 22%, showing a significant benefit per subscale in 100% (8), 87.5% (7) and 62.5% (5) of users from Group 1 in the respective subscales FC, RV and RA. On the other hand, no significant benefit was obtained from the SA subscale for this Group. Now, 83.33% (15) of Group 2 users presented effective benefits in subscales FC and RA, 72.23% (13) for RV, 5.56% (1) for subscale SA .In the Global assessment, a real performance improvement, that is, an index with hearing aid that was 10% better than the index without hearing aid in the three subscales FC, RV, and RA was seen in 75% (6) of those patients from Group 1; 2 users had benefits above 10%, in 82.35% (14) of the individuals who made up Group 2, and the other two presented lower benefits only in subscale RV, and a third one without significant benefits in the three subscales .Thus, the APHAB questionnaire proved to be an excellent tool, not only o assess the benefit obtained from the use of amplification, but also to predict and confirm the user’s performance when in difficulty of communication in different situations, which still remain despite the use of amplification, thus contributing in adjusting amplification throughout the process, because as we can see in this study, the rehabilitation process is directly linked to the expectations and perceptions of the user herself, and this is the keystone in the hearing aid fitting process.The aim of the hearing aid fitting process is to offer environment sound amplification and mainly the sounds of speech in a satisfactory and proper manner. Nonetheless, even with amplification, some communication difficulties may depend on hearing loss type, level and configuration, as well as disabilities and auditory handicap experienced by the patient. Therefore, such aspects not only have to be taken into account, but also challenged together with the future user, so that a high expectation with rehab does not impair the real benefit obtained with amplification.Once again, we stress that the use of these protocols in the pre and post fitting periods, since they proved to be excellent predictors of the difficulties faced by the users of hearing aids, could also help in adjusting the device based on the user’s own perception, however in a quantified and standardized way, often times by means of spontaneous questions - these users feel intimidated or unable to reveal their own difficulties.By the same token, even if the prescribed acoustic gain values are reached or the speech recognition tests show improvements in speech recognition, the self-assessment questionnaires must be used, since an increase in hearing and/or speech recognition do not guarantee a reduction in the hearing disability handicap the patient experienced. We also consider that the education and advice stage, as well as long term advising, is mandatory to assure a successful rehabilitation, soothing out the difficulties that may eventually slow down treatment progress.At the end of this study, a critical appreciation of the results led us to conclude that:1.The self-assessment questionnaires proved to be excellent predictors of the difficulties faced by the users of hearing aids, and they could also help in hearing aid fitting;2.Significant differences between the groups studied in the self-assessment HHIE S and HHIA protocols, as well as in the APHAB were not found, except in the ease of communication subscale, in which Group 1, without complaints related to amplification characteristics obtained greater benefits.


Hearing loss is the most common neurosensory disorder, and with the constant increase in etiological factors, combined with early detection protocols, numbers will continue to rise. Cochlear implantation has become the gold standard for patients with severe hearing loss, and interest has shifted from implantation principles to the preservation of residual hearing following the procedure itself. As the audiological criteria for cochlear implant eligibility have expanded to include patients with good residual hearing, more attention is focused on complementary development of otoprotective agents, electrode design, and surgical approaches. The focus of this review is current aspects of preserving residual hearing through a summary of recent trends regarding surgical and pharmacological fundamentals. Subsequently, the assessment of new pharmacological options, novel bioactive molecules , nanoparticles, stem cells, and gene therapy are discussed. Hearing loss is the most common neurosensory disorder when considering all sensory deficits and carries a tremendous economic and social burden, considerably impacting patients’ quality of life.In recent decades, hearing loss has become an increasingly concerning health issue. According to the World Health Organization, around 466 million people worldwide have disabling hearing loss  has become the gold standard of treatment and is constantly being improved and adapted to patients’ actual needs. Given the results obtained since the initial implementation in 1971 [As we witness a steady increase in knowledge regarding the inner ear’s physiology and with the development of targeted therapies, many lines of research regarding CI and ways to increase its functionality are being explored. However, few of these results will actually reach mass adoption and clinical usage. Many of the novel treatment options are in accordance with the Gartner Hype Cycle for Emerging Technologies, but only a few will prove their actual benefit. Thus, we believe that a review of the current knowledge is necessary to sum up the principles that are being considered for future implementation. Through this review, we outline the surgical principles of CI, with emphasis on recent technical improvements, and discuss emerging therapies focused on improving the outcomes of cochlear implantation.As selection criteria for CI are continuously evolving and more patients are eligible for implantation, the preservation of residual hearing is becoming increasingly studied. Sustained trauma to the cochlea during the advancement of the electrode array was identified as a critical factor that can deteriorate residual hearing; therefore, in recent years, increasing attention has been focused on the surgical procedure.The aim of preserving residual hearing led to an emphasis on avoiding mechanical trauma to the cochlea, leading to the use of the term ‘‘soft’’ surgical technique. After the first mention of the soft-surgery concept by Lehnhardt in 1993 , severalCochlear implantation most commonly begins with cortical mastoidectomy followed by posterior tympanotomy and preparation of the device well. Non-mastoidectomy approaches, such as the pericanal approach, the suprameatal approach, and the transcanal approach, still require drilling to create the groove that shelters the electrode . One priNoise and vibration during surgical drilling has become a concern for the potential reduction in residual hearing. Pau et al. determined that drilling at the level of the promontory exceeds 100 dB SPL, with further increased SPL when the endosteal layer is exposed, and exceeding 130 dB SPL when the round window membrane is touched by the drill . VibratiThe use of hyaluronic acid (HA) in cochlear implantation is not a new concept, as Donnelly demonstrated it in 1995 by using HA to facilitate electrode insertion into fresh human temporal bone specimens . Other aAnother emerging surgical concept is that of partial electrode insertion in patients with residual hearing who are candidates for electric–acoustic stimulation. Lenarz et al. hypothesize that partial electrode insertion could offer protection for the lower frequencies, and if hearing loss progresses postoperatively, the electrode can be further inserted .Intraoperative electrocochleography (ECochG) has been utilized during CI surgery and can provide the surgeon objective feedback during electrode insertion. Although it is not a method used to reduce inflammatory reaction by itself, whenever ECochG amplitude or phase responses are modified, the surgeon can adjust the course of the electrode in order to obtain normal intracochlear potentials and limit potential physical trauma to the cochlea .In addition to the soft surgery principles, it has been hypothesized that applying hypothermia to the surgical site has the potential to reduce immediate and delay secondary hearing loss. In preclinical studies, local application of controlled hypothermia rendered a protective effect by decreasing the auditory function loss associated with electrode insertion ,19. TakiThe cochlear implant electrode array is positioned in the scala tympani when normal anatomy is present. The round window membrane or a basal turn cochleostomy are the two most common ways to access the scala tympani in order to insert the electrode array . Each haThe round window membrane (RWM) is a natural boundary of the scala tympani. It has become an increasingly popular route for electrode insertion in cochlear implantation, particularly for hearing preservation. Preliminary comparisons revealed that the round window approach causes much less traumatic than insertion through a cochleostomy . DrillinRobotics in neurotology is a relatively recent subject is intended to help with various aspects of cochlear implant surgery, such as drilling a keyhole route to the middle ear for implants, inner ear access, and electrode insertion into the cochlea . InsertiEarly experimental studies on cadaveric cochleae revealed that robotic-assisted insertion systems reduced cochlear trauma associated with CI electrode insertions compared to manual insertions ,31. CompFollowing the first reports of cochlear implantations using robot-assisted electrode insertion, the results obtained after a radiological and audiological evaluation showed that this technique is less traumatic ,33,34. ATorres et al. also described their experience using straight and pre-curved electrodes but did not correlate the electrode type results, instead emphasizing the electrode array’s scalar translocation and functional outcomes. They observed no differences in speech perception in a sound-isolated room between manual electrode array insertion and robot-assisted techniques. However, they did observe that robot-assisted insertion reduced the number of translocated electrodes compared with manual insertion  but lackAs this new technique is promising, studies are still needed to determine safety, utility recommendations, and cost effectiveness. Further developments in robotic technologies and more clinical evidence may convert this surgical approach into a feasible, affordable option. Meanwhile, using intraoperative ECochG during CI surgery can offer the surgeon objective feedback during electrode insertion.Current surgical principles are outlined in The pharmacological substances with the best results in the preservation of post-implantation hearing are yet to be determined. The same also applies to the dose, delivery, and the timing of administration for currently available pharmacological substances.As the passing of the electrode through the scala tympani initiates a foreign body inflammatory reaction, pharmacological compounds with anti-inflammatory properties are among the most studied. The most well-known and scrutinized pharmacological compounds for this purpose are still corticosteroids. Their efficacy inspired their use in various hearing preservation protocols in an attempt to decrease any incidental loss of hearing . AlthougThe authors of one study recommend using intravenous (i.v.) dexamethasone one hour before surgery in order to reduce possible surgery-induced hearing loss ; others Although topical administration of steroids hypothetically implies higher intracochlear concentrations , animal To obtain the best functionality from a cochlear implant, preservation of the spiral ganglion neurons (SGN) is also of utmost importance, along with the cochlear components, as they are the target of electrical stimulation . Rejali Glial-cell-line-derived neurotrophic factor (GDNF) and BDNF attached to the cochlear implant electrode via biodegradable calcium phosphate hollow nanospheres also induced spiral ganglion nerve axons to sprout and grow towards the electrode to form direct contact and close the anatomical gap between them .Neurotrophin-3 (NT-3) was studied alongside BDNF or as a standalone substance. Through an experimental animal study using guinea pigs, Pfings et al. delivered intracochlear NT-3 via a viral vector, followed by cochlear implantation. Results were compared to empty viral vector inoculation and cochlear implantation, as well as cochlear implantation without inoculation. Overall results show that NT-3 cochlear inoculation was effective in maintaining a higher number of SGN compared to implanted cochleae with empty virus inoculation and implanted cochleae with no inoculation. Unfortunately, in the subjects with NT-3 inoculation, SGN preservation in the vicinity of the cochlear implant variated from 4% to 49% in animals with no residual hearing and between 4% and 67% in animals with residual hearing. These inconsistencies in SNG density could be an effect of NT-3 or could be derived from electrical stimulation of the implant, which is known to sustain nerve function; therefore, further studies with no electrical stimulation are needed .Various studies have been conducted on the mechanism of insulin growth factor 1 (IGF-1) and its role as a neurotrophic agent with anti-inflammatory properties capable of inhibiting apoptosis and promoting cell regeneration, making it a potential inner ear protector ,52,53,54Inhibitors of the c-Jun N-terminal kinase-like CEP-1347, SP 600125, and D-JNKI-1 have been investigated as antiapoptotic substances in preclinical and clinical studies since 1900 ,60,61. DD-JNKI-1was investigated in a phase III clinical trial, HEALOS , for acute sensorineural hearing loss (ASNHL). The intratympanic AM-111 administration was well tolerated and safe but failed to meet the study’s primary endpoint. Analysis of pure-tone average (PTA) scores revealed significant hearing recovery in the profound idiopathic sudden sensorineural hearing loss (ISSNHL) subpopulation but not in the severe ISSNHL subpopulation . To datePioglitazone is an antidiabetic drug of the thiazolidinediones (TZDs) class used to treat type 2 diabetes mellitus. TZDs act by activating peroxisome proliferator-activated receptors (PPARs), a group of nuclear receptors exerting an anti-inflammatory and antiproliferative effect, as well as regulating the cellular redox balance. When used with gentamicin in in vitro studies conducted by Sekulic-Jablanovic et al., pioglitazone demonstrated a protective cochlear effect against oxidative stress and prevented gentamicin toxicity ,68. As PIn 2018, pioglitazone was included as a 1.2% gel injection compound in a phase III multicentric, double-blind, placebo-controlled clinical trial  including adults with sudden sensorineural hearing loss. Participants were randomly allocated to one of three groups: intratympanic pioglitazone gel injection (STR001-IT) followed by 12 weeks of 5mg sustained-release oral pioglitazone tablets (STR001-ER), intratympanic pioglitazone followed by 12 weeks of oral placebo treatment, and intratympanic placebo injections followed by 12 weeks of oral placebo treatment. Results have yet to be published . No precOther PPAR activators, such as fenofibrate, rosiglitazone, and other antidiabetic drugs, including metformin, are mentioned in the literature as having an otoprotective effect, but none of them have been studied in conjunction with cochlear implants ,73,74,75N-acetyl cysteine (N-ACC) is a precursor and the substrate for glutathione synthesis, an endogenous antioxidant. When studied with noise-induced cochlear damage, N-ACC reduced reactive oxygen species (ROS), protected mitochondria, and inhibited inflammation and necrosis . When stAn in vivo animal study conducted by Eastwood et al. using a pledget loaded with N-ACC applied on the round window for 30 min before cochleostomy and electrode insertion brought up some detailed information. Whereas local N-ACC exposure led to a non-significant change in threshold shift in the low and mid frequencies, the high frequencies exhibited an increased threshold shift in the first week after surgery, with complete resolution by the fourth week compared to saline. Although there were no signs of active inflammatory reaction, the experimental group did display signs of ossification .The results of a 2021 in vivo study contradicted the favorable effects of N-ACC in vitro. Jaudoin et al. prepared an N-ACC liposomal gel, which was applied transtympanically one week before and during cochlear implantation. After seven days, the hearing thresholds increased in all frequency ranges compared with the group with no N-ACC. When tested on normal hearing guinea pigs, the liposomal gel induced a hearing loss that remained constant until the following two weeks of the study . These oTaurodeoxycholic acid, a bile acid taurine conjugate of deoxycholic acid, was used by Shah et al. in an in vitro study mimicking EIT. By analyzing apoptosis, levels of ROS, nitric oxide, and hair cell (HC) density, the authors observed that TDCA protected against HC loss in a dose-dependent manner .A summary of all the pharmaceutical agents described above is presented in When opting for a cochlear implant as a therapeutic solution for hearing loss, access to the inner ear is created through the round window or a cochleostomy; therefore, the electrode can also support local drug delivery to reduce EIT in order to avoid high systemic drug concentrations with possible adverse effects, blood labyrinthine barrier (BLB) limitation, or the “first-pass” effect . The desGlucocorticosteroids were intensively studied to reduce EIT and DEX-eluting electrodes, resulting in a considerable amount of research data ,88,89,90Chen et al. used an electrode coated with polycaprolactone (PCL) loaded with 5%, 10%, and 20% DEX to obtain prolonged release. In an artificial perilymph, the electrode released a stable DEX concentration for up to 270 days with no toxicity for the HEI-OC1 cell line. At five weeks after CI, they measured a minor ABR threshold shift in favor of the PCL-DEX-coated electrode when compared to the uncoated electrode. They also observed reduced cochlear fibrosis and better preservation of the SGNs .The first human study with a dexamethasone-eluting cochlear implant electrode elaborated by MED-EL (CIDEXEL) is an ongoing clinical trial that began in June 2020 , with no results available yet.As SGNs seem to be protected by brain-derived neurotrophic factor (BDNF) or neurotrophin 3 (NT3), implanting electrode arrays coated with fibroblasts overexpressing these neurotrophins appears to be a therapeutic alternative for EIT and residual hearing preservation ,50.PLGA-coated electrode arrays treated with DEX, aracytine (Ara-C), Ara-C+DEX, and nicotinamide adenine dinucleotide (NAD+) were used recently in an animal study . The ABRHydrogel-coated electrodes filled with recombinant human IGF1, recombinant human growth factor (HGF), a mixture of both were implanted into guinea pig cochleae by Kikkawa et al. . The coaAs researchers noted that systemic drug delivery into the cochlea was hindered by the limitations mentioned earlier and that local RW application limited permeation into the inner ear, new methods of drug deliveries emerged. One of the main focuses is on loading drugs into/onto nanoparticles (NPs). The use of these nanovectors has been investigated due to their promise for improved drug stability, increasing drug storage capacity, and improving target specificity .BDNF is a macromolecule whose delivery to the inner ear can improve the electrode–neural interface after a cochlear implantation. Nanoporous silica and nanoporous poly-L-glutamic acid (PGA) nanoparticles were studied for this task . Wang etPoly-L-glutamic acid can also be used as a building block for BDNF carriers. Nanoporous PGA particles encapsulating BDNF demonstrated a protective effect on the spiral ganglion neurons after intracochlear administration . No studOne study was intended to improve the functionality of cochlear implantation using rolipram delivered into the cochlea through a lipidic nanocapsule. An interesting observation of this study was that rolipram alone did not to improve ABR results, but the lipid nanocapsule containing rolipram increased the spiral ganglion survival rate .The aim of regenerative medicine applied to hearing loss is to restore hearing without the need for a hearing aid. Currently, regenerative therapies are combined with cochlear implants to improve their functionality. When used as monotherapy, stem cells offer limited benefits and have reduced capacity to restore cochlear function .As repopulation of the cochlea with hair cells with the help of stem cells is technically complex, increasing the population of spiral ganglion neurons appears more feasible in the initial stages. Following this principle of SGN repopulation, stem cells can be associated with CI to achieve better outcomes. BDNF-overexpressing mesenchymal stem cells (MSCs) introduced into a guinea pig cochlea as a CI electrode coated with ultra-highly viscous alginate were more effective in protecting SGNs from degeneration compared to BDNF injected before CI insertion .Roemer et al. described a protocol for elaborating biohybrid cochlear electrodes using autologous mononuclear cells derived from bone marrow (BM-MNC). The authors chose this cellular line for its immunomodulation, neuroprotection, neurorestorative, and neurogenesis properties. Before clinical use, they evaluated cytotoxicity in an in vitro model and studied the insertion forces in a 3D human cochlear model. Three candidates for contralateral cochlear implantation were included in the clinical trial. The authors compared the performance of the biohybrid electrode to that of the contralateral standard non-coated cochlear implant. Whereas none of the patients manifested adverse reactions and the electrode impedances were identical between the ears, speech perception was similar in both ears in just one patient. A second patient’s speech perception in the biohybrid electrode-implanted ear exceeded that in the contralateral ear, whereas speech perception was reduced in the third patient . AlthougWith the advancement of gene sequencing methods, we can now identify a consistent number of genes linked to inherited hearing loss . As hearIn order to deliver in vivo cochlear gene therapy, a vector is needed. Two main platforms can be differentiated: viral vectors  and non-viral vectors  . The uniAs some of these vectors can be administered transtympanically for an indirect diffusion into the inner ear, a direct access into the cochlea is desirable through the round RWM, the oval window (OW), cochleostomy, or through a semicircular canal.Gene therapy was combined with a cochlear implant by Pinyon et al. in 2014, using a guinea pig model . They usNeurotrophin-3 and BDNF have both been proven to be important for SGN growth, survival, and regrowth ,106,107.Simultaneous hearing loss restoration strategies are being developed as we witness rapid technological and biological progress. All of these efforts combined and implemented could greatly benefit patients in the future.Improved electrode designs, surgical advancements, and microsurgical and robotic instruments will make otologic surgical procedures less traumatic, more accurate, and tailored to each patient’s unique anatomy and needs. Surgical principles are clearly outlined based on current concepts. In the case of robotic surgery utility, guidelines need to be further presented, and cost effectiveness has to be taken into consideration. Locally applied hypothermia is a feasible option due its current use in other surgical areas and due to the fact that is does not present a side-effect profile.As new drugs with otoprotective properties are studied and new implant materials are developed, cochlear implant drug delivery opens new possibilities for the immediate short-term future. To date, many of the researched substances have not been tested in clinical trials. The only pharmaceutical agent being tested in a clinical trial is MAPK/JNK pathway inhibitor, but the study is not associated with cochlear implantation. Corticosteroids are the only compounds that are frequently used as a potential agent for the preservation of residual hearing, but no clear evidence suggests that one administration route or dose is more favorable than the others.When improved understanding of nanotechnologies, gene treatments, and stem cells is achieved, construction of a bionic ear could become more compelling. At present, most of these therapies are experimental, as there are still ethical issues (stem cell therapy), as well as toxicity, stability (nanoparticles), and efficiency issues to be addressed.


Background and Objective: Cancer survival has improved significantly, which reflects the achievements in screening, diagnosis, and treatment. As a consequence, multiple primary malignancies are diagnosed more frequently, with an incidence ranging from 0.52–11.7%. The types of malignancy that coexist and survival patterns vary notably in different countries and geographical areas. Due to the limited literature in Saudi Arabia, a baseline of prevalent malignancy combinations and their survival patterns would support early detection and disease management. Method: This was a retrospective descriptive study conducted from 1993–2022 at King Abdulaziz Medical City, Department of Medical Oncology, Riyadh, Saudi Arabia. Patients with at least two biopsy-proven solid malignancies were included. Patients with hematological malignancies, missing data, or an uncertain or indecisive pathology report were excluded. Result: In total, 321 patients were analyzed. More than half (57.3%) of the patients were female. A third (33%) of the cases were synchronous, and 67% were metachronous. The most frequent site of the first primary malignancy was breast cancer, followed by colorectal, skin, and thyroid cancers. The most frequent site of the second primary malignancy was colorectal cancer, followed by thyroid, breast, and liver cancers. Only 4% of the cases had a third primary malignancy, with colorectal and appendiceal cancers being the most frequent. The most frequently observed histopathology in the synchronous and metachronous malignancies was adenocarcinoma. Breast–colorectal, breast–thyroid, and kidney–colorectal were the most frequently observed malignancy combinations. Conclusion: The current study offers a baseline of multiple primary malignancies in Saudi Arabia and provides supporting evidence that the pattern of multiple primary malignancies varies among different countries and ethnicities. The possibility of developing another primary malignancy should be considered when treating and monitoring cancer patients. Cancer is the second most frequent cause of mortality, and a major burden that is increasing globally ,2. In 20Multiple primary malignancies (MPMs) are a frequently encountered phenomenon, with an incidence ranging from 0.52–11.7% ,10,11. TAlthough information regarding MPMs is not well-established, they can be a consequence of aging, chemoradiation for the first malignancy, an underlying genetic susceptibility, environmental exposures, immunosuppression, lifestyle factors, or hormonal factors . ImmunocThe prognosis of MPMs relies mainly on the type and stage. It is not clear whether having multiple malignancies alters the patients’ prognosis. Even though the samples in most of the literature were small, data suggest that having a short interval between malignancy diagnoses, defined as 60 months, is a poor prognostic factor. Additionally, the literature indicates that the rate and survival of metachronous malignancies are higher than those of synchronous malignancies ,13,14,18Since geographical differences in the MPM rate, survival patterns, and types have been described in other countries, it is worth assessing the rate of synchronous and metachronous malignancies, as well as survival and distribution, in male and female patients in Saudi Arabia. An in-depth evaluation of this phenomenon would provide a baseline for the careful monitoring of patients treated for a particular primary cancer and ensure the early detection and treatment of other primary cancers.The objective of this study was to evaluate the mortality rate and distribution of the malignancies based on gender and the diagnosis time interval, malignancy combinations, and survival patterns in Saudi patients with biopsy-proven MPMs and to determine the prevalence of MPMs in Saudi Arabia.This was a descriptive, single-center, retrospective study conducted at King Abdulaziz Medical City (KAMC), Department of Medical Oncology, Ministry of the National Guard-Health Affairs, Riyadh, Saudi Arabia. KAMC is an academic, government-funded tertiary hospital that combines clinical care, training, academics with research, and state-of-the-art medical technologies.Initially, the Department of Medical Oncology tumor registry at KAMC identified a total of 25,276 oncology patients from 1993–2022. Then, 450 patients with at least two biopsy-proven malignancies were extracted. After that, the research team screened the 450 cases, and only 321 were eligible for inclusion. The included patients had to be Saudi with at least two biopsy-proven solid malignancies. Patients with hematological malignancies, such as leukemia, lymphoma, plasma cell dyscrasias, and myeloproliferative neoplasms, were excluded. The patients with missing or uncertain data, benign tumors, suspected malignancies, a lack of pathology reports, or indecisive pathology reports, were excluded Data from 1993 to 2015 were collected from the data management system of the Department of Medical Oncology at King Abdullah Specialized Children’s Hospital, KAMC. Data from 2016 to 2022 were obtained by screening the electronic records  of the cases that were identified by the tumor registry. The collected data included gender, first and second anatomical and histopathological diagnoses, the date of each diagnosis, date of last seen/last follow-up or date of death, and survival status. A synchronous malignancy was defined as a second malignancy that occurs either simultaneously, or within 6 months after the first malignancy diagnosis, and a metachronous malignancy was defined as a second malignancy at least 6 months after the first malignancy diagnosis.p < 0.05.The Statistical Package for the Social Sciences (SPSS) version 22  was used for data analysis. The categorical variables were presented as frequency and percentage, and the numerical variables as mean ± standard deviation. The time interval between the first and second primary diagnoses was presented as median and percentiles . The prevalence of MPMs was calculated by dividing the number of MPM patients prior to applying the aforementioned exclusion criteria (450) over the total number of oncology patients , and then multiplying by 100 (1.78%). The survival times were calculated from the date of diagnosis of the first primary malignancy to the date of death or date of last follow-up. The survival probabilities for the synchronous and metachronous malignancies were estimated using the Kaplan–Meier method. The log-rank test was used to compare the survival times between different groups. Results were considered significant if The study was approved by the Institutional Review Board of King Abdullah International Medical Research Center, Ministry of the National Guard-Health Affairs, Riyadh, Saudi Arabia (NRC22R/083/02). Because of the retrospective nature of the study, informed consent was waived. Access to the data was restricted to the researchers. The confidentiality of all patients was protected; no names or medical record numbers were used. Privacy and confidentiality were assured, and all the data, both hard and soft copies, were kept in a secure place within the National Guard-Health Affairs premises.n = 184) of the patients were female. Only 4.0% (n = 13) of the cases had triple primary malignancies, with colorectal (n = 4) and appendiceal (n = 2) cancers being the most frequent third primary diagnoses. The other third primary diagnoses were gastric, liver, prostate, bladder, and cervical cancers (n = 1 for each). The prevalence rate of MPMs was 1.78%. The mean age at diagnosis of the first, second, and third primary malignancies was 59.3 ± 14.3, 62.7 ± 13.4, and 71.9 ± 6.5 years, respectively, with a median of 61 , 63 , and 74 , respectively. A third  were synchronous, and 66.7% (n = 214) were metachronous, with a median diagnostic interval of 1.72  years. The overall mortality rate was 37.4% (n = 34), breast (n = 26), kidney (n = 24), thyroid, and liver (n = 22 for both) malignancies, and the most frequent metachronous malignancies were colorectal (n = 70), breast (n = 61), thyroid (n = 46), and skin (n = 33) malignancies. The most frequently observed histopathology for both synchronous and metachronous malignancies was adenocarcinoma (n = 10), breast–thyroid (n = 10), kidney–colorectal (n = 8), colorectal–breast (n = 7), colorectal–kidney (n = 7), thyroid–colorectal (n = 7), skin–liver (n = 7), and ovary/testis–thyroid (n = 6) (p = 0.002) (p = 0.928) (p = 0.002)  . The med= 0.002) . The med= 0.928) . If clas= 0.002) A,B.Cancer-related mortality decreased by 29% in 2017 compared to 1991, reflecting significant achievements in cancer screening, prevention, diagnosis, and treatment, ,21 whichAlthough information regarding MPMs is limited, several risk factors have been identified, including aging, genetic susceptibility, chemotherapy such as doxorubicin and cyclophosphamide, radiation, immunosuppression, and smoking ,18,24,25In the current study, MPMs were more prevalent in the females (57.3%) than in the male patients (42.7%), which is not supported by the literature ,11,12,26Only 4.0% of our sample had triple primary malignancies, in agreement with the literature ,28. The Our results showed that 33.0% of the cases were synchronous, with 67.0% being metachronous malignancies. This pattern is consistent with the literature, as synchronous MPMs range from 30.0–55.0% ,32,33. TIn the current study, breast cancer was the most frequently diagnosed first primary malignancy, followed by colorectal, skin, thyroid, kidney, and liver cancers, accounting for 16.5%, 15.6%, 8.1%, 6.9%, 6.9%, and 5.9%, respectively. This is probably unique to the Saudi population, as definite geographical differences exist in different populations and countries. To emphasize, based on the results of two Turkish studies, the most frequent first primary malignancies were head and neck, breast, colorectal, bladder, and gastric cancers ,37. In IIn China, the most frequently diagnosed first primary metachronous malignancies were colorectal, head and neck, and lung cancers, and the most frequently diagnosed first primary synchronous malignancies were lung, colorectal, and breast cancers ,12,38. OIn our study, the most frequently observed histopathologic morphology in synchronous and metachronous malignancies was adenocarcinoma. The histopathologic morphology in patients with MPMs is not always reported in the literature. A Chinese study reported that adenocarcinoma was the most frequent histopathological diagnosis in both the synchronous and metachronous groups, followed by squamous cell carcinoma ,40.In the current study, the most frequently observed malignancy pairs  were breast–colorectal, breast–thyroid, kidney–colorectal, colorectal–breast, colorectal–kidney, thyroid–colorectal, and skin–liver. Based on a Turkish study, the most frequently observed malignancy pairs in males were head and neck–lung, bladder–lung, bladder–prostate, and prostate–lung. For females, the most frequently observed malignancy pairs were breast–gynecologic, colorectal–breast, breast–colorectal, gynecologic–breast, and mesenchymal malignancy combinations . Althougp = 0.002). This is in agreement with the literature reporting worse survival with synchronous malignancies [In this study, the median survival time was 9.2 and 13.2 years for synchronous and metachronous malignancies, respectively, and the difference was statistically significant (gnancies ,42. A pognancies ,43. The gnancies .The current findings indicate geographical differences in different countries. Although the number of people surviving cancer is increasing, the burden of cancer will continue to grow as the likelihood for subsequent primary cancers increases. An important contribution of the current findings is raising awareness among oncologists, with increased attention and suspicion of particular malignancies that are more likely to coexist synchronously or metachronously. In terms of future research, it would be useful to extend the current findings by examining the association in these paired malignancies, the complications, and therapeutic implications in order to improve the findings of this descriptive and single-center study. Despite these limitations, the present study enhanced our understanding of the probability of the coexistence of particular malignancies in Saudi Arabia. We hope that the current research will encourage future researchers to investigate this important area.The most frequent site of the first primary malignancy was breast cancer, followed by colorectal, skin, and thyroid cancers. The most frequent site of the second primary malignancy was colorectal cancer, followed by thyroid, breast, and liver cancers. Only 4.0% of the cases had a third primary malignancy, with colorectal and appendiceal cancers being the most frequent third primary diagnoses. The most frequent malignancy combinations were breast–colorectal, breast–thyroid, kidney–colorectal, colorectal–breast, colorectal–kidney, thyroid–colorectal, and skin–liver. The synchronous malignancies had a lower survival time. The possibility of developing another primary malignancy should be considered when treating and monitoring cancer patients.


The concept of “green biosynthesis”, as well as the similar and more general concept of “green synthesis”, is collective and includes very diverse synthetic methods, using products vital for activity from various living organisms—of both plant and animal origin—for chemical compound production. This synthesis variant is an integral part of one of the youngest sections in modern chemical science, namely green chemistry (sustainable chemistry), which, according to the IUPAC definition, is “Design of chemical products and processes that minimize or eliminate the use or generation of substances hazardous to humans, animals, plants, and the environment” ,2. This The development of processes to maximize the number of raw materials that enter a product;The use of renewable raw materials and energy sources;Using safe, environmentally friendly substances, including solvents, whenever possible;The design of energy-efficient processes;The prevention of waste generation, which is considered an ideal form of waste management.Historically, green chemistry arose and was developed from the many existing ideas and research efforts in the period preceding the last decade of the XX century in the context of increasing attention being paid to pollution and environmental problems and natural resource depletion. The ideological basis of this specific chemistry branch was mainly formed in the second half of the 1990s, and the wider spread of this term meant that it eventually began to prevail over “competing” terms such as “pure” and “stable” chemistry ,4. ShortThe last few decades have been marked by the very significant application of “green biosynthesis” to solve various problems related to the nanotechnology field, namely, to obtain various nanoparticles and study the physicochemical processes associated with them. It should be noted here that the analysis of links, including keywords related to green technologies in the main databases, since the appearance of the 12 principles in 1998, shows the scale of work related to this topic  Table 1Table 1. In recent years, it is clear that this publication number has sharply increased  over the period 2015–2022. Additionally, there is no doubt that a very significant number of articles devoted to the biosynthesis of elemental silver nanoparticles was published in journals not indexed in Scopus, as well as in other sources of scientific information. Moreover, “green biosynthesis” was used not only in reference to silver nanoparticle synthesis, but also in reference to other, very diverse chemical compounds, which is why the number of articles related to this theme will almost certainly be in six figures. Thus, it is extremely important to study the «green synthesis» specifics and the compounds obtained on its basis and to develop the scientific principles for its further use primarily in the so-called life sciences—for the treatment of different diseases, the creation of new drugs, the fight against a variety of infectious agents, etc.Although in “green biosynthesis”, living organisms and/or products of their vital activity are used to produce nanoparticles, many chemical reactions take place during this process. The whole set of chemical reactions can be divided into two main categories, namely, reactions that change the oxidation degree of the chemical elements included in the substances participating in the reaction  and reactions that do not change the oxidation degrees of chemical elements. In “green biosynthesis”, chemical transformations in both categories can be realized, but the reactions in the first category, known by the generalized term redox reactions (or redox processes), are the most commonly used here. The vital activity products of living organisms are overwhelmingly reducing agents , whereas substances used to produce target compounds , on the contrary, are oxidizers . The mechanism of nanoparticle synthesis in the framework of redox processes includes three stages : (1) actThe interpretive problem of physical and chemical processes arising within the “green biosynthesis” associated with a wide variety of involved biochemical reagents. This problem is the most essential; despite significant progress in this research, the nanoparticle biosynthesis mechanism is not fully understood, and accordingly, the controlling possibilities in this process are still very limited. First, it concerns “green biosynthesis”, when redox reactions are realized. Biomolecules capable of metal ion reduction and forming nanoparticles are already known for plant biosynthesis, but the involved compounds’ use as capping agents requires further study, because frequently, these molecules’ roles in the biological properties of potentially used nanoparticles are extremely varied. Using microorganisms as a factory for nanoparticle production requires special condition selection—temperature, pH, and a clear knowledge of the biomolecules involved in this process. In addition, for an adequate interpretation of the “green biosynthesis” process mechanism, it is absolutely necessary to analyze all of these features at the quantitative level, which seems to be an extremely difficult task.The problem associated with the purification of the resulting nanoparticles. Nanoparticles and materials based on them produced by “green biosynthesis”, as a rule, carry a specific memory about their origin prehistory, i.e., they contain a fairly significant number of organic impurities. Sometimes, they can be useful because they contribute to enhancing their biological activity . However, quite often, they can increase the aggregation of nanoparticles, which usually worsens their inherent useful properties. As a result, the problem of removing such undesirable impurities from nanoparticles has become particularly urgent and cannot yet be considered satisfactorily solved. Thus, research with the aim of improving existing and developing new methods for isolating nanoparticles from the systems where they were formed is very important.A problem related to the reproducibility of biosynthesis results. It is possible to control the nanoparticle formation process via chemical and physical methods (with varying reliability) to eventually obtain nanoparticles which are standardized in shape and size. It is much more difficult to achieve this via “green biosynthesis” due, firstly, to the large number of factors affecting the final result, and secondly, the fluctuations associated with them being much more pronounced. Accordingly, the result reproducibility achieved via this synthesis variant is significantly worse than that achieved via chemical and physical methods. For “green biosynthesis”, information regarding the influence of concentration–time and temperature parameters used during the experiment is extremely necessary. However, in most published works, this information is scattered and clearly insufficient for far-reaching conclusions to be drawn. If this problem is solved, it will facilitate standardized preparation production containing nanoparticles, including for commercial purposes. On the other hand, it would be extremely significant to solve this problem, as it would enable the maximum output of a target product to be achieved.In this way, we hope that this Special Issue will make at least a small contribution to this specific and important branch of modern “green chemistry”. Further research which appears in this direction, with the aim of not only solving the problems outlined above, but also exploring other themes related to nanoparticle production, may serve to increase the popularity of the biological synthesis method among researchers working in the field of nanoscience and nanotechnology.


The comorbidities associated with varicose veins were deep vein thrombosis (p = 0.001), hypertension (p = 0.002), chronic constipation (p = 0.006), diabetes (p = 0.001), kidney disease (p = 0.001), rheumatoid arthritis (p = 0.001), coronary artery disease, and severe occupational injury to the lower extremities (p = 0.001). Nurses are responsible for most of the health system's services. Increasing the number of nursing workers for patient care, encouraging physical exercise, and lowering the pension age appear to be required to avoid the occurrence and development of varicose veins among nurses.Varicose veins (VV) in the lower limbs are the most prevalent vascular condition in humans. They can cause significant signs and symptoms and, in extreme cases, death. This study aims to investigate the prevalence and identify the risk factors for varicose veins among nurses working in multiple departments at Jazan King Fahd Central Hospital and Prince Muhammad bin Nasser Hospital. A cross-sectional study was conducted by sending a questionnaire to female and male nurses in these hospitals. This study included 482 nurses, 415 (86.1%) of whom were female and 67 (13.9%) male. The prevalence of varicose veins among the nurses of both hospitals was 76 (15.8%), compared with 406 (84.2%) not diagnosed with varicose veins. The prevalence of varicose veins was 67 (88.2%) in female nurses, compared with 9 (11.8%) in male nurses. The risk factors associated with varicose veins were ethnicity ( Varicose veins (VV) in the lower limbs are the most prevalent vascular condition in humans, causing significant signs and symptoms and, in extreme cases, death ,2. VV isNumerous factors may contribute to the valves' weakening and failure, including genetics, venous thrombosis, and the loss of the elastic tissue of the venous wall . In the The examination of varicose veins should be conducted while standing in good light to determine the degree and size of the varicose veins and the presence of other venous disorders. The presence or absence of venous hypertension-related skin injuries is the most critical medical concern . ContinuNurses are critical components of healthcare systems, and lower leg varicose veins may result in performance instabilities and increased economic expenditures by people and society to remedy the imposed damage. The issue is essential, as it may imperil work production, health in old age, various underlying thrombotic events, and other grave consequences . This stStudy design and areaA cross-sectional study was conducted at King Fahd Central Hospital and Prince Muhammad bin Nasser Hospitals in Jazan province. Jazan  is one of the 13 provinces of the Kingdom of Saudi Arabia (KSA). It is located in the southwest of the KSA and is highly populated with 1.5 million residents.Identification of study participantsThe sample size was calculated using the Raosoft online calculator, and it was estimated to be 482 nurses. The sampling was divided into males and females and stratified according to different departments at King Fahd Central Hospital and Prince Muhammad bin Nasser Hospital.Inclusion and exclusion criteriaAll hired nurses of both genders working in administrative or clinical positions were included in the study. Pregnant nurses and nurses under the age of 18 years were excluded.Data collection processThe demographic , behavioral (smoking daily or exercising), physical (height), and work-related variables (sitting and standing periods during work hours and handling heavy objects) sections of the questionnaire were all subjectively assessed by the participants. Health-related data  were also included in the questionnaire. We started collecting data after receiving approval from the Institutional Review Board (IRB) of the Jazan Health Ethics Committee; the approval number is 2197.Data analysisThe data obtained were analyzed using the Statistical Package for Social Sciences (SPSS) software . Before entering the data into SPSS, it was cleaned and described using descriptive statistics. To specify categorical variables such as gender and race, frequencies/percentages were employed. The mean and standard deviation explained quantitative variables such as weight, height, and birth rate. The chi-square or Fisher's exact test determines the associations between the outcomes and any categorical variables. A p-value of 0.05 was used for statistical significance.This study included 482 nurses, of whom 415 (86.1%) were female and only 67 (13.9%) were male. Almost all participants were Arabian  with 106 (22%) Asian. Two hundred fifty-four (52.7%) were married, 217 (45%) were single, 9 (1.9%) were divorced, and 2 (0.4%) were widowed. More than half of the nurses worked at King Fahd Central Hospital , while 239 (49.6%) nurses were from Prince Muhammad bin Nasser Hospital. The prevalence of varicose veins among the nurses of both hospitals was 76 (15.8%), compared with 406 (84.2%) not diagnosed with varicose veins. Four hundred four (83.8%) were nonsmokers; only 78 (16.2%) of the participants were smokers. Almost half of all participants did not play sports , while 206, (42.7%) did four times or less weekly. The majority of participants, 71 (35.5%), had been working for one to four years, and 136 (28.2%) had been working for five to nine years. Many of the nurses, 152 (31.5%), worked five shifts weekly, and 105 (21.8%) worked three shifts weekly  in female nurses, compared with 9 (11.8%) in male nurses. Fifty-one (67.1%) of the nurses diagnosed with varicose veins were married, compared with 24 (31.6%) single and 1 (1.3%) divorced. The number of positive responses for varicose veins working at King Fahd Central Hospital was 41 (53.9%). The prevalence of varicose veins was high in nurses carrying heavy items: 52 (68.4%). The incidence of varicose veins was higher for participants who did not play sports - 48 (63.2%) - compared with 35 (36.8%) for nurses who did. Only seven (9.2%) nurses diagnosed with varicose veins had been working for less than one year; in contrast, 27 (35.5%) participants diagnosed with varicose veins had been working for between five and nine years. Twenty-four (31.6%) nurses with varicose veins worked five shifts weekly, and 15 (19.7%) worked six shifts weekly. Thirty-two (42.1%) participants with varicose veins did not have children, compared with 44 (57.9%) who had children. Furthermore, 104 (25.6%) nurses were not diagnosed with varicose veins but were suspected of having varicose veins.The risk factors associated with varicose veins were ethnicity (p=0.007), lifting heavy objects (p = 0.001), lack of exercise (p = 0.031), family history (p = 0.001), use of hormonal therapy (p = 0.001), use of contraceptive pills (p = 0.0035), type of delivery p = 0.002), and number of children (p = 0.004). All these risk factors indicate statistically significant associations with varicose veins. The varicose vein predictors that were not statistically significant (p > 0.05) were gender, social status, place of work, number of shifts, years of work, and smoking. The comorbidities associated with varicose veins were deep vein thrombosis (p = 0.001), hypertension (p = 0.002), chronic constipation (p = 0.006), diabetes (p = 0.001), kidney disease (p = 0.001), rheumatoid arthritis (p = 0.001), coronary artery disease, and severe occupational injury to the lower extremities (p = 0.001). All these diseases had statistically significant associations with varicose veins , height was 158.3 ± 8.3 cm versus 159 ± 21.9 cm (p = 0.788), and weight was 62.8 ± 16.6 kg versus 62.1 ± 14.4 kg (p = 0.715). Moreover, the hours standing per shift was 7.8 ± 4.2 hours versus 7.5 ± 3.1 hours (p = 0.497), the number of gravida was 2.68 ± 1.5 versus 2.32 ± 1.4 (p = 0.286), the number of parities was 1.89 ± 0.76 versus 1.91 ± 0.96 (p = 0.926), and the number of abortions was 1.25 ± 0.45 versus 1.65 ± 1.18 (p = 0.253). All these variables did not exhibit a statistically significant correlation with varicose veins (p > 0.05). However, the hours of sitting per shift was 4.5 ± 3.8 hours versus 3.1 ± 3 hours (p = 0.002), indicating statistically significant with varicose veins  were gender, social status, place of work, number of shifts, hours standing per shift, years of work, and smoking. Age, sex, and ethnic origin were shown to be risk factors for varicose veins in most previous research . In our Ethnicity was considered a risk factor for varicose veins in this study, as 88.2% of nurses who had varicose veins were Arabian, compared with 10.5% Asian and only 1.3% African. However, these findings were not valid and could not be inferred since the number of participating nurses significantly varied by ethnicity. Mekky et al. reported that varicose veins were investigated in 504 female cotton workers in England and 467 female cotton workers in Egypt. Varicose veins were far more prevalent in the English mill population than in the Egyptian community .The nurses with a family history had more varicose vein incidents (64.5%) than the nurses who did not have a family history (35.5%). Cornu-Thenard et al. studied 143 families, including 67 patients and their parents and 67 controls and their parents. A total of 402 patients were tested. The findings indicated that inheritance had a significant impact on the development of varicose veins (p = 0.001). Children had a 90% chance of acquiring varicose veins if both parents had the illness, 25% for men and 62% for females if only one parent had it, and 20% for neither parent .In this research, 68.4% of participants diagnosed with varicose veins usually lift objects that weigh 23 kg or more during work time and lift heavy objects such as electronic devices and equipment like kidney machines and oxygen tanks. Moreover, carrying the patient to transfer him from one ward to another ward increases pressure on the lower limbs and leads to vascular wall and valvular damage. The research by Tabatabaeifar et al. corroborated our study in that the prolonged lifting of large things was associated with varicose veins and a higher risk of surgical therapy . In our The nurses who delivered vaginally had a higher chance of developing varicose veins than the nurses who delivered through C-sections. Additionally, the females with children had a greater risk than the females who did not. This is because when a female is pregnant, progesterone levels rise, and the uterine wall expands, increasing blood volume and potentially resulting in valve failure. Jawien et al. reported that varicose veins were more prevalent in women than in males. The number of pregnancies (more than two pregnancies) considerably separated women with and without varicose veins .When we compared the nurses with varicose veins and those without varicose veins according to the continuous variables, we found that age (p = 0.101), height (p = 0.788), weight (p = 0.715), and hours standing per shift (p = 0.497) did not show statistically significant associations with varicose veins (p > 0.05). The number of hours sitting per shift was statistically significant (p = 0.002). Chen and Guo reported that in a comparison of hairdressers regarding varicose veins, those with lower limb varicose veins had longer work histories , higher ages , and worked more hours standing each month  . Our stuIn our study, the comorbidities associated with varicose veins were deep vein thrombosis (p = 0.001), hypertension (p = 0.002), chronic constipation (p = 0.006), diabetes (p = 0.001), kidney disease (p = 0.001), rheumatoid arthritis (p = 0.001), coronary artery disease, and severe occupational injury to the lower extremities (p = 0.001). This conclusion was consistent with the report by Bermudez et al. that insufficiency in deep veins was higher in traumatized limbs than in non-traumatized limbs . VaricosNurses are responsible for most of the health system's services. Increasing varicose intensity can impair work output, threaten physical and mental health - particularly in older adults - and impose high costs on individuals and healthcare systems. Based on the results of this study, increasing the number of nursing workers for patient care, encouraging physical exercise, and bringing the pension age forward appear to be required to avoid the occurrence and severity of varicose veins.LimitationsThe study's limitations include the tiny sample size. The cross-sectional design precluded the investigation of variations in varicose veins over time. Additionally, we were unable to ascertain the participants' lifestyle and exercise habits. Furthermore, this research included nurses from two hospitals only; therefore, the findings may not be generalizable to other populations.This cross-sectional study contributes to the knowledge of the prevalence and risk factors for varicose veins. Our study has revealed a low prevalence of varicose veins among nurses working at King Fahd Central Hospital and Prince Muhammad bin Nasser Hospital. The prevalence of varicose veins was higher in females than in males. The varicose vein risk factors were ethnicity, lifting heavy objects, lack of exercise, family history, use of hormonal therapy, use of contraceptive pills, type of delivery, the number of children, and hours sitting per shift. The comorbidities associated with varicose veins were deep vein thrombosis, hypertension, chronic constipation, diabetes, kidney disease, rheumatoid arthritis, coronary artery disease, and severe occupational injury to the lower extremities. Nurses are responsible for most health system services, and hiring more nursing workers for patient care, promoting physical exercise, and lowering the pension age seems to be required to prevent the occurrence and development of varicose veins.