PD can ameliorate cisplatin-induced hearing loss through activating the Nrf2/HO-1 signaling pathway. This study provides a potential strategy for preventing and improving hearing loss resulted from cisplatin treatment in clinics.Irreversible sensorineural hearing loss is one of the most common side effects after cisplatin treatment. Prevention and reversal of hearing loss caused by cisplatin are of great importance for cancer patients, especially children. Oxidative stress is an important cause of hearing loss resulted from cisplatin, unfortunately, there is no drug yet available that can completely prevent and reverse the ototoxicity from cisplatin. Polydatin (PD) possesses excellent antioxidant and anti-inflammatory effects, however, its role in the cisplatin-induced hearing loss has not been investigated. Herein, we have explored the preventive and therapeutic effects of PD on cisplatin-induced hearing loss and the possible underlying mechanisms. In the  Cisplatin is one of the effective chemotherapy drugs for a broad spectrum of tumors . OtotoxiThe mechanism of cisplatin-induced hearing loss remains unclear. Oxidative stress injury, inflammation, apoptosis and autophagy play an important role in the pathogenesis of cisplatin-induced hearing loss . Reactivvia enhancing the activity of sirtuin 1 in a mouse model , also named piceid , is a natural active ingredient extracted from polygonum cuspidatum, a traditional Chinese medicinal plant. PD possesses the effects of anti-inflammatory, anti-oxidative stress, anti-ischemia injury, anti-atherosclerosis, anti-apoptosis, anti-tumor, anti-bacteria, and anti-virus, which has garnered considerable attention . PD is ase model . After iioxidant .The mechanisms of PD functions in different experimental settings were partially investigated. Through the Nrf2/HO-1 signaling pathway, PD was reported to improve the spinal cord injury in rats by inhibiting oxidative stress and microglial apoptosis  and to aNrf2, as an important transcription factor regulating cellular oxidative stress response, plays an important role in maintaining cellular redox homeostasis . Nrf2 alIn this study, we aimed to explore the effects of PD on cisplatin-induced hearing loss, and attempted to unravel the underlying mechanism. First, we evaluated the changes of Nrf2, HO-1, caspase-3 and iNOS in the cochlea before and after cisplatin administration with a guinea pig model. The expression of caspase-3 and iNOS in the cochlea was declined with the application of PD, which promoted the expression of Nrf2 and HO-1, thereby inhibiting oxidative stress injury caused by cisplatin. PD may become a new strategy to prevent and treat cisplatin-induced hearing loss by activating the Nrf2/HO-1 signaling pathway.ad libitum. This experiment protocol was approved by the Animal Ethics Committee of the Third Affiliated Hospital of Southern Medical University and strictly abided by animal ethics norms. 56 Guinea pigs were randomly divided into the following eight groups, 1) control group, 2) cisplatin (CDDP) group, 3) solvent +CDDP group, 4) 40 mg/kg PD group, 5) dexamethasone (Dex) +CDDP group, 6) 20 mg/kg PD + CDDP group, 7) 40 mg/kg PD + CDDP group, 8) 80 mg/kg PD + CDDP group, n = 7 for each group, respectively.In this study, male adult hartley guinea pigs (250 ∼ 350 g) were purchased from the Animal Experimental Center of Southern Medical University. Each guinea pig underwent auricle reflex and electric otoscope examination to exclude external auditory canal lesions and otitis media. Animals were kept in a temperature-controlled environment (23°C), fed under standard 12-h light/dark conditions with access to food and water, PD  solution, dexamethasone sodium phosphate injection  and cisplatin  were used in this study. 2% (v/v) DMSO in saline was used to dissolve PD. Control group received 1.0 ml of normal saline [intraperitoneal injection (i.p.)] every day for 3 days. PD group was administered with PD  for 3 days. CDDP group was administered with cisplatin  once and then normal saline  every day for 2 days. Solvent + CDDP group was administered with solvent 1 h before cisplatin  was injected and then normal saline  every day for 2 days. PD group was administered with PD  for 3 days. DEX group was administered with DEX  1 h before cisplatin  was injected and then DEX  every day for 2 days. 20 mg/kg PD + CDDP group was administered with PD  1 h before cisplatin  was injected and then PD  every day for 2 days. 40 mg/kg PD + CDDP group was administered with PD  1 h before cisplatin  was injected and then PD  every day for 2 days. 80 mg/kg PD + CDDP group was administered with PD  1 h before cisplatin  was injected and then PD  every day for 2 days. On the third day after drug administration, guinea pigs were anesthetized with 1% pentobarbital sodium at a dose of 40 mg/kg for evaluation.Auditory brainstem response (ABR) test was performed in a sound-proof electrical shielding room on an ABR recording system (Tucker-Davis Technologies). The recording electrode was placed in the middle of the cranial top at the midpoint of the upper edge of the bilateral auricle. The reference electrode was placed under the donor ear, and the grounding electrode was placed under the contralateral ear. ABR thresholds were measured with click and tone bursts at 4, 8, 16, 24, and 32 kHz, respectively. Stimulus level decreased in 10 dB steps and then in 5 dB steps near threshold. The hearing threshold is determined based on wave III and defined as the lowest stimulus level that elicited a reproduceable waveform with identifiable peaks. ABR threshold was detected 24 h before and 72 h after drug administration in each group.After the guinea pigs were sacrificed by injection of excessive anesthetics, four cochleas in each group were harvested, fixed in 4% buffered paraformaldehyde for 12 h, and decalcified in 10% EDTA for 14 days, and embedded in paraffin according to the reported method . Samples2 . The software then calculated the area within the outline. SGN density was measured as the number of SGNs per mm2 . One secAdditional cochleas of the control group and CDDP group were taken for scanning electron microscopy (SEM) to observe the hair cells (HCs) damage. SEM of the cochlea follows these steps, cochlea dissection, fixation of the tissue at 2.5% glutaraldehyde, gradient dehydration of samples, cochlear microanatomy to expose the basilar membrane by removing the volute and tectorial membrane, critical point drying, gold sputter coating, and scanning using the Hitachi SU8100 electron microscope. We assessed the integrity of the HCs in the basilar membrane of the cochlea and the morphology of the stereocilia on the HCs.Five cochleas in each group were harvested, fixed in 4% buffered paraformaldehyde for 12 h, and decalcified in 10% EDTA for 7 days. After 1 week of decalcification, the basilar membranes of each turn were carefully separated from the worm shaft and divided into four sections according to a line . All the above operations were performed under an anatomical microscope . After rinsing with PBS, sections were stained with FITC-phalloidin (1:100) for 30 min. The basilar membrane was carefully spread on the glass plate after rinsing with distilled water three times, and the excess water was dabbed with filter paper, and then the antifade mounting medium  was added dropwise and sealed. Digital images were captured under a fluorescence microscope  and OHCs counts were performed using ImageJ .For immunostaining of Nrf2, HO-1, caspase-3 and iNOS, cochlear sections were rehydrated before the antigen retrieval process (0.01 M sodium citrate pH 6.0 for 2 min in the microwave oven). After washing with PBS, tissues were blocked in 5% normal goat serum for 30 min and in the diluted primary antibody  overnight at 4°C. The next day, the slides of Nrf2 and HO-1 were washed extensively and appropriate fluorescently labeled secondary antibodies  were applied for 1 h at 37°C. Meanwhile, the slides of caspase-3 and iNOS were washed extensively and appropriate fluorescently labeled secondary antibodies  were applied for 1 h at 37 °C. All slides were then washed thoroughly and treated with DAPI  for DNA visualization. Cover slips were mounted with the antifade mounting medium  to inhibit fluorescence quenching. Digital images were taken under a fluorescence microscope .Three dissected cochleas in each group were collected on ice, stored at −80°C, and lysed using a RIPA buffer . The concentration of the extracts was determined with the Micro BCA kit . Protein samples were separated with sodium dodecyl sulfate polyacrylamide gel electrophoresis and transferred to a PVDF membrane , which were blocked with 5% nonfat dry milk in TBS with 0.1% Tween-20. The membranes were incubated with primary antibodies, namely rabbit anti-Nrf2 , anti-HO-1 , anti-caspase-3 , anti-iNOS  and anti-β-actin  overnight. After incubation with the secondary antibody , and extensive membrane washing, the blots of immune reactivity were illustrated through enhanced chemiluminescence . ImageJ  was used for densitometric comparisons. β-actin density measurements were used as loading controls.post hoc test was employed. p < 0.05 was considered statistically significant.GraphPad Prism 8.0 software  was used for statistical analysis. Data were presented as mean ± standard error of the mean (SEM). Multiple comparisons were assessed using one-way or two-way analysis of variance (ANOVA), and the analysis of variances followed by Tukey’s p = 0.053). Overall, our results suggest that PD (40 mg/kg) has the best hearing protection efficacy in our experimental animal model.In order to investigate the effect of PD on auditory function, we recorded the ABR threshold and threshold shift of eight different groups 24 h before and 72 h after cisplatin administration . The selFor the purpose of further exploring the protective effect of PD on hearing loss, we observed the morphological changes of the cochlea with H&E staining . The numIn order to further explore the protective effect of PD on auditory function, we evaluated the survival of HCs on the basilar membrane. First, SEM of the cochlea was used to determine the damage of HCs after cisplatin administration. In our results, HCs on the basilar membrane of the control group were arranged neatly, without loss of cells , and theWe dissected the basilar membrane of cochlea and stained with FITC-phalloidin then observed and counted HCs under fluorescence microscope, so as to further explore whether the damage of HCs in each group matched the hearing loss and whether PD played a protective role in hearing by alleviating the damage of HCs. In the gross anatomy of the guinea pig cochlea, the basilar membrane of the cochlea can be divided into four turns, turn 1, turn 2, turn 3 and turn 4, which correspond to red, blue, purple and yellow respectively . ObservaOxidative stress injury in cochlea is an important pathway of ototoxicity induced by cisplatin, we performed immunostaining of antioxidant factors (Nrf2 and HO-1), apoptosis markers (caspase-3) and iNOS to investigate the mechanism of PD in hearing protection. Cisplatin induced hearing loss is often accompanied by apoptosis of SGNs and HCs in the cochlea. Therefore, we first detected the expression of caspase-3 . In the We further detected the expression of Nrf2 . In the We focused on the defense mechanism of Nrf2/HO-1 in order to gain a deeper understanding of the molecular mechanism of PD on hearing protection. In the control group, Nrf2 was slightly expressed in the cytoplasm , as showp < 0.001) (p < 0.001)  group. In the CDDP group and solvent + CDDP group, the expression of Nrf2 and HO-1 increased , accompa< 0.001) . In addi< 0.001) . The posSensorineural hearing loss is the most common type of hearing loss, including noise hearing loss, age-related hearing loss and drug-induced hearing loss . These tIn our animal model, cisplatin induced acute hearing loss 3 days after administration, presenting with increase of ABR thresholds and a large loss of OHCs, which was consistent with the reported results . Cisplatin vivo (PD is a natural active ingredient extracted from traditional Chinese medicinal plant polygonum cuspidatum. It has been widely acknowledged due to its anti-inflammatory, anti-oxidative stress, anti-ischemic injury, anti-atherosclerosis, anti-apoptosis, anti-tumor, antibacterial and antiviral effects . As the in vivo . Howeverin vivo . Moreovein vivo , suggestTo treat and alleviate cisplatin-induced hearing loss, it is essential to unravel the underlying mechanism of the effective antioxidant. Nrf2 is a transcription factor encoded by NFE2L2 gene and plays an important role in regulating redox homeostasis . In humain vivo. It increases the residence time of cisplatin in animal models, more similar to clinical regimens (It should be noted that compared with single high-dose systemic injection or administration through circular window membrane in previous studies, three-cycle cisplatin administration is an ideal and clinically relevant animal model system for studying cisplatin-induced ototoxicity and screening otoprotective drugs regimens . It is nCisplatin often causes damage to OHCs and spiral ganglion cells, resulting in hearing loss. PD, as a natural extract of traditional Chinese medicine, can alleviate cisplatin-induced acute hearing loss. PD may activate the transcription and expression of HO-1 and other downstream antioxidant factors by promoting the nuclear translocation of Nrf2, thereby reducing oxidative stress injury in cochlea and reducing the apoptosis of OHCs and SGNs caused by NO and caspase-3. In summary, to our knowledge, it is first report to demonstrate the effect of PD on reducing cisplatin-induced hearing loss and its possible underlying mechanism, providing a new strategy for clinical prevention and treatment of cisplatin-induced hearing loss.


Experimental and clinical data suggest a tight link between hearing and cognitive functions under both physiological and pathological conditions. Indeed, hearing perception requires high-level cognitive processes, and its alterations have been considered a risk factor for cognitive decline. Thus, identifying common pathogenic determinants of hearing loss and neurodegenerative disease is challenging. Here, we focused on redox status imbalance as a possible common pathological mechanism linking hearing and cognitive dysfunctions. Oxidative stress plays a critical role in cochlear damage occurring during aging, as well as in that induced by exogenous factors, including noise. At the same time, increased oxidative stress in medio-temporal brain regions, including the hippocampus, is a hallmark of neurodegenerative disorders like Alzheimer’s disease. As such, antioxidant therapy seems to be a promising approach to prevent and/or counteract both sensory and cognitive neurodegeneration. Here, we review experimental evidence suggesting that redox imbalance is a key pathogenetic factor underlying the association between sensorineural hearing loss and neurodegenerative diseases. A greater understanding of the pathophysiological mechanisms shared by these two diseased conditions will hopefully provide relevant information to develop innovative and effective therapeutic strategies. Numerous clinical and epidemiological studies have highlighted a tight association between hearing loss and cognitive decline ,2,3,4. AHearing ability is essential in everyday life, ensuring environment interaction, the identification of damaging stimuli, cognitive ability , and, not least, social interaction. The auditory system, which is highly complex anatomically and physiologically , allows A simplified model of the ascending auditory pathway is shown in red. The neural signal travels from the cochlea to the ventral and dorsal cochlear nuclei (VCN and DCN). Next, some of the axons cross the midline to the superior olivary complex (SOC), terminating in the inferior colliculus (IC) and to the medial geniculate body (MGB). Other fibers project ipsilaterally to SOC and IC, terminating MGB. Then information reaches the auditory cortex (ACx). Note that the ACx can send and receive information from the hippocampus (HP) directly or through the entorhinal cortex (EC). The descending auditory pathway is shown in black. Corticofugal projections from the ACx reach IC, SOC, and cochlear nuclei, modulating cochlear response.Sensorineural hearing loss (SNHL) is the most common sensory disorder in humans: it has been estimated to affect about 360 million people worldwide, and more than half of the population over 60 years of age reports hearing impairment ,41. SNHL2+ influx and glutamate excitotoxicity [Among the different exogenous damaging factors leading to hearing impairment, noise exposure is the most common cause of acquired SNHL in industrialized countries ,43. Of ntoxicity ,61. Clintoxicity .+ channels expression and activity [Susceptibility to NIHL differs among individuals due to a combination of genetic and environmental factors. It has been estimated that the heritability of NIHL is ~36% . Howeveractivity ,64,65. Factivity ,66, giveactivity ,28,67.ARHL, or presbycusis, refers to the age-dependent decline in hearing sensitivity, leading to an increased auditory threshold in aged subjects. In the United States, more than 50% of people over 70 years show ARHL . MoreoveAhl1), localized in chromosome 10, Ahl2 [Ahl3 on chromosome 17 [Ahl allele, such as the C57BL/6 mouse model, are considered valuable models of ARHL [Gjb2) and gap junction protein beta-6 (Gjb6) genes, encoding connexin 26 (Cx26) and connexin 30 (Cx30), respectively, have been linked to the deafness DFNB1, the most frequent non-syndromic hearing loss in the Mediterranean population [Gjb2 and Gjb6 mutations are candidate genetic risk factors for ARHL.Studies in presbycusis patients have estimated that from 25% to 75% of the variance in this pathology has a genetic component . Researcosome 17 . Thus, m of ARHL ,77. Varipulation . Recent pulation , whereaspulation . Moreovepulation . Namely,Increasing evidence from both clinical and animal studies indicates that events and injuries occurring in life may contribute to the vulnerability of inner ear structures to aging processes ,70,82. AIt has been reported that hearing impairment causes alterations in both auditory and “extra-auditory” brain regions involved in the non-lemniscal path, such as the hippocampus ,88. Inde2•−), hydroxyl radical (•HO), and singlet oxygen (1O2), as well as non-radical species such as hydrogen peroxide (H2O2) formed by the partial reduction of oxygen [Oxidative stress refers to the failure of the redox balance between the production of oxidants and the antioxidant defense system activity . It has f oxygen ,119. Thef oxygen . ROS canf oxygen . Indeed,f oxygen ,121. Morf oxygen ,123. Indf oxygen . mtDNA if oxygen . Thus, Rf oxygen . ROS-indf oxygen .In physiological conditions, maintaining a redox balance ensures an adequate intracellular ROS level, which is essential to regulate signaling pathways ,128 and Because of their high oxygen consumption, high lipid content, abundant mitochondria, and high energy requirement, neurons and hair cells are particularly vulnerable to damage caused by ROS. Oxidative stress has been proposed to be the pathogenic core of both SNHL  and neurCochlear mechanoelectrical transduction is a complex mechanism that requires high metabolic demands to maintain large electrochemical gradients, which is essential for mechanoelectrical transduction. The high metabolic demand, in turn, renders the cochlear structures particularly vulnerable to oxidative stress damage. Indeed, it has been demonstrated that alteration in redox balance leads to oxidants accumulation, damaging several elements such as sensory cells, stria vascularis, and afferent neurons, causing cell death and hearing loss ,131,132.2+ storage in the endoplasmic reticulum, resulting in an exciting cytosolic Ca2+ load. In response to cytosolic Ca2+ increase, endogenous GSH levels are reduced, and the cellular free radical amount rises [2+ modulation [Neurodegenerative diseases refer to several uncurable and debilitating pathological conditions, including AD, Parkinson’s disease (PD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS), and others, characterized by progressive damage in neural death, responsible for alterations in motor or cognitive functions . The patnt rises . Similarnt rises . In turnnt rises ,176. Aβ nt rises  by incrent rises . Accordint rises . The rolnt rises ,180. Mornt rises . As descnt rises ,182. Addnt rises . Moreovent rises , suggestdulation . It has dulation  affects dulation , probabldulation . Aβ-indudulation ,188; in dulation . Furtherdulation , which fdulation . Finallydulation ,193. Neudulation , which pdulation . Indeed,dulation . Moreovedulation ,198, anddulation ,200.Among the potential theories proposed to explain the link between sensorineural hearing loss and dementia, the existence of a possible common pathogenetic mechanism affecting the auditory periphearl organ (the cochlea), causing hearing loss, and barin structures (hippocampus), causing cognitive decline, has been considered . As discIt has to be considered that hearing loss induced by noise or aging causes an up-spread deafferentation in the auditory system ,90, so tOf course, a deeper understanding of the molecular mechanism relating to hearing loss and hippocampal dysfunction is needed, and further works on this topic are necessary to shed light on the role of oxidative stress as a common pathological marker linking hearing loss and dementia.Considering the prominent causal role of oxidative stress in the pathogenesis of hearing loss and dementia, several studies addressed the possibility to target redox unbalance in cochlear or brain structures to counteract oxidative stress ,224,225,2O2, and hydrogen radicals and it is considered a major contributor to the maintenance of cellular GSH, acting as a substrate for its synthesis [Among all molecules with antioxidant activity, N-acetyl, L-cysteine (NAC) is probably the most studied against noise-induced oxidative stress. Indeed, NAC has been tested in several experimental conditions, animal models, and dosages ,227,228.ynthesis . Interesynthesis . The effynthesis .Vitamin E is considered one of the most important antioxidants in the brain, especially the α-tocopherol form . The proAmong direct scavenger modules, we studied the antioxidant ability of Coenzyme Q10 (CoQ10), as well as its analog Idebenone and its soluble form Q-ter, against cochlear oxidative insult ,244,245.Collectively, clinical and experimental evidence suggests a strong link between hearing and cognition, so hearing loss has been considered one of the main modifiable risk factors for cognitive decline. In this review, we discussed data showing that oxidative stress similarly impinges on inner ear and brain structures involved in cognitive functions by common pathogenic mechanisms. Thus, redox imbalance represents a key determinant of the vicious cycle between hearing loss and cognitive impairment both during “physiological” aging and in neurodegenerative diseases. A greater understanding of the molecular determinants and intracellular pathways linking hearing loss and dementia can have a crucial impact on treatment and prevention of these oxidative stress-dependent neural dysfunctions. Antioxidant therapy to counteract both hearing loss and cognitive impairment is a promising approach, also given the possibility of using dietary antioxidants such as polyphenols. However, further research is needed to understand in greater details the mechanisms linking cochlear and brain vulnerability to oxidative stress and to overcome antioxidant treatment limits, including low bioavailability.


Dining establishments are an essential part of the social experience. However, they are often characterized by high levels of background noise, which represents a barrier to effective communication. This particularly affects people suffering from hearing problems. Moreover, noise level exceeding normal conversational levels causes a phenomenon called the Lombard Effect, an involuntary tendency to increase the amount of vocal effort when talking in the presence of noise. Adults over 60 years represent the second largest population in the US and the majority of them suffer from some degree of hearing loss. The primary aim of the current study was to understand the effect of noise on vocal effort and speech intelligibility in a restaurant setting for adults over 60 years old with and without hearing loss. The secondary aim was to evaluate their perception of disturbance in communication and their willingness to spend time and money in a restaurant was affected by the varying levels of background noise. The results of this study showed background noise levels lower than 50 dB(A) will allow senior customers to minimize their vocal effort and to maximize their understanding of conversations, even for those with moderate to severe hearing loss. By setting a limit, it will also keep perceived disturbance low and willingness to spend time and money high among dining patrons. Beyond the basic purpose of restaurants to provide food and drink, restaurants have, historically, fulfilled a human need for connection and shaped social relations. However, restaurants are often characterized by high level of background noise that negatively affect the communication.1. A restaurant’s atmosphere is vital to keeping and enticing new patrons, which can cause the diners to increase their overall bill at a restaurant2. However, depending on the age group, several individuals might recall the noisy environment more than the food3. This is especially problematic for patrons aged 60 and older suffering from hearing loss, as background noise interferes with the comprehension of conversations6.Before the 1990’s, “excessive” restaurant noise was not negatively perceived by diners and critics because it was supposed to add to the atmosphere of the eating establishment7. Restaurants are designed to look aesthetically pleasing and modernized, which often is portrayed with a lack of materials used to absorb sound. The lack of these materials tends to increase the overall noise level in the restaurant which has caused diners, critics, audiologists and researchers to take notice12. In 2018, a repeated restaurant survey revealed noise was the primary complaint of restaurant patrons12. Restaurants have a wide range of noise during hours of operation, which has caused restaurant critics to carry sound level meters to evaluate the noise levels to include in their reports1. Typical restaurant noise can fluctuate throughout the course of an evening ranging from 65 dB(A) up to as high as 85 dB(A)13. This causes increased difficulty to be heard and understood by anyone13. The main source of noise in a restaurant is caused by the patrons, as a consequence several researches suggested that dining establishments should no longer be thought to have “maximum capacity” but rather “acoustical capacity”10. The maximum capacity can be defined as the number of seats occupied within the restaurant space, in order to retain efficiency and safety to both the workers and patrons. The acoustical capacity is instead defined as “the maximum number of persons in a room for sufficient quality of verbal communication;” it can be calculated using the volume of the room (m) and the reverberation time (s) of the unoccupied, furnished restaurant setting6. It is possible to maximize the acoustical capacity by making design adjustments like carpeting, sound absorbent panels, or curtains on the walls and ceilings15.In recent years, there has been increased awareness towards the acoustics of eating establishments with the goal of improving speech intelligibility18. The typical slope for the Lombard Effect is 0.3–0.6 dB in voice increase per dB in noise increase, when the noise exceeds 50 dB(A)20. In a recent study, Bottalico21 investigated the Lombard Effect values in restaurant settings, using typical restaurant noise in a laboratory. During the experiment, the author presented recorded restaurant noise at varying sound pressure levels from 35 dB(A) to 85 dB(A) with 5 dB increments to normal hearing college students. After reading a short passage (The Rainbow Passage)22, in each noise condition, participants were asked to score their perceived disturbance, how much time they would stay, and how much money they would be willing to spend. The results indicated a change-point of the Lombard Effect at 57.3 dB(A), with a slope of the lower segment being 0.31 dB/dB and the upper segment as being 0.54 dB/dB slope. Additionally, the college students’ scores for disturbance, time, and money started to decrease at 52.5 dB(A) (disturbance=52.2 dB(A), willingness=51.3 dB(A), money=52.5 dB(A)). The results form Bottalico21 had some limitations: (1) college students do not spend much dining out potentially due to lower income24, and (2) younger adults have a greater tolerance to loud sounds25. For this reason, this study will focus on adults older than 65 years.The presence of high level background noise in an environment, where communication is key, often triggers the Lombard Effect. The Lombard Effect is the involuntary tendency of the speaker to increase the vocal effort, while speaking in loud noise27; and by 2030, 19.3% of the population will be adults aged 65 years and older in the United States28. The National Institute on Aging (NIA) estimates there are approximately 49 million Americans aged 65 and older, which is the largest number of older adults than any other time recorded in history29. Recently in research, there has been an increased demand to better understand the process of aging to assist this population, not just in terms of healthcare29, but also to keep them connected to society27.Over the last hundred years, life expectancy has increased upwards of thirty years31 and voice disorders32, which are prevalent amongst older adults. The World Health Organization33 estimates approximately 60% of adults aged 60 and older will experience an age-related hearing loss at a degree of moderate loss or greater. It is possible the combination of high noise levels in the restaurant, in conjunction with hearing problems, makes conversing difficult for them to partake in and comprehend34.This population of older adults (aged 65+) has been shown to have a lower tolerance to loud sound versus their younger counterparts. This could be contributing to the cause of why older adults are choosing to avoid dining out. Another reason could be that there are several comorbidities, such as high-frequency hearing lossWith the goal of understanding how the senior population will react to noise in a restaurant setting, in terms of voice production (the Lombard Effect) and speech perception (the Cocktail Party Effect), the following research will investigate five different outcomes. The aim of this study will attempt to answer the following research questions: (1) What is the level of noise at which older adults experience the Lombard Effect? (2) What is the relationship perceived amount of disturbance and noise level in a restaurant for older adults? (3) How much time would older adults be willing to stay in restaurants with different noise levels? (4) How much money would they be willing to spend? (5) What is the noise level at which older adults are no longer able to have an intelligible conversation?32. (2) Older adults will perceive a greater disturbance than the young adult group, due to younger adults’ lesser likelihood of peripheral hearing loss and more reliable auditory processing abilities35. 3) Older adults’ willingness to spend time and money will decrease as the noise increases, due to their dislike of louder noise levels while dining out5. 4) Older adults will perform poorer on intelligibility as the noise increases, due to their recorded peripheral hearing loss, lack of amplification to assist in preservation of word understanding abilities, and their general decrease in cognition specifically for selective attention, working memory, and auditory closure abilities. 5) The degree of hearing loss will amplify the aforementioned effects.The hypotheses of the current study are: (1) Older adults will have a lower Lombard Effect than the previous young adult group, as a result of aging and decreased vocal effortp values are given in Table A piecewise linear  models appear to be the best fits in comparison to simple linear models and quadratic models. The goodness of the fit was evaluated based on the R-squared, the analysis of the residuals, and the fact that the use of a more complex model did not improve the fit in a statistically significant way. The Delta SPL was measured at each of the 11 noise levels between 35 and 85 dB(A), as shown in Fig. p values are given in Table Self-reported communication disturbance was measured at each of the 11 noise levels Fig. , panel ap values are given in Table The willingness to spend time in the restaurant was measured at each of the 11 noise levels, as shown in Fig. p values are given in Table The willingness to spend money in the restaurant was measured at each of the 11 noise levels, as shown in Fig. p values are given in Table The intelligibility in the restaurant was measured at each of the 11 noise levels, as shown in Figure The aim of this study was to identify which levels of background noise are affecting negatively the dining experience for adults over 60 years with and without hearing loss. The parameters analyzed were objective, i.e. Lombard Effect and speech intelligibility, and subjective, i.e. the perceived disturbance, the willingness to spend time and the willingness to spend money. The long-term goal of this project is to increase noise awareness in crucial environments for social life, such as restaurants, in order to create age-friendly communities.21, there was no definitive starting point for the Lombard Effect in older adults, and a similar change-point was found at a noise level of about 57–58 dB(A). This noise level threshold is in agreement to previous reports of the Lombard Effect’s starting point occurring between 40–60 dB(A)20. College students and older adults showed a similar trend of increased vocal effort as the noise levels increased from 35 dB(A) to 85 dB(A). The Lombard Effect for older adults was slightly lower than the one for college students ; this is supporting the hypothesis in which vocal fatigue and aging influence the overall vocal effort of older adults32. The vocal behavior of the participants was not statistically different in the three different groups of hearing loss, which can be explained by previous research about the effect on hearing loss on voice production. Coelho et al.36 found that individuals with mild and moderate hearing loss can only present problems with resonances of the vocal tract, while severely impaired individuals may lack intensity and frequency control. Because among our participants only two had a severe hearing loss, it was predictable that the voice loudness would have not change among the three groups.Regarding the relationship between noise and voice level (the Lombard Effect), the hypothesis that “older adults will have a lower Lombard Effect than college students”, was verified. Similarly, to the results of BottalicoThe hypotheses concerning disturbance, time, and money were confirmed: (1) the amount of older adults’ disturbance increased with the noise and (2) the willingness to spend time and money decreased as the noise increased. The communication disturbance perceived by the participants increased with noise starting from the lowest level of noise. At 51.6 dB(A), the slope of this relationship increased dramatically till a saturation point for the disturbance at 66.9 dB(A).The relationship of the willingness to spend time in the restaurant with the background noise level in the restaurant showed one breakpoint at 65.8 dB(A). A saturation effect for noise levels higher than the breakpoint was present in the relationship. It appears that since from low background noise levels, participants were annoyed by it. However, once the noise was exceeding the breakpoint, participants reported that they would have left the dining facility as quickly as they had entered.The relationship of the willingness to spend money in the restaurant with the background noise level in the restaurant showed two breakpoints with the lower segment ending at 54.6 dB(A) and an upper segment starting at 62.0 dB(A). Between those two levels, the willingness to spend money in the restaurant decreased quickly with a slope of − 4% of the budget per dB(A) in noise increase. Once the noise was exceeding 62.0 dB(A) participants reported that they would have spent less than 25% of their budget.21 where college students’ judgments were minimally impacted by noise levels lower than 50−55 dB(A). These differences between older and younger adults could be explained by their higher sensitivity to louder noise levels of older adults compared to the sensitivity of younger adults25.The results in terms of communication disturbance, willingness to spend time and willingness to spend money were significantly different if the participants were suffering from hearing loss (both mild and moderate-to-severe). Participants with normal hearing were better in tolerating the background noise levels. On equal noise conditions, they were less disturbed and willing to spend more time and money in that restaurant compared to participants with hearing loss. The present results also differ from the results of BottalicoNoise significantly influenced intelligibility and the following hypotheses were confirmed: (1) older adults performed worse on intelligibility as the noise increased and (2) the higher the degree of hearing loss the lower their overall intelligibility performance. Figure 37. In the present study, the participants did not use hearing aids, even if few of them were using them in their daily life. This represents a limitation to the ecological validity of the study. However, we considered that there are an estimated 22.9 million older Americans with audiometric hearing loss who do not use hearing aids38. Finally, even if presented in previous papers, the subjective evaluations of the disturbance in communication and the willingness to spend time and money in a restaurant were not externally validated and they can all be representative of the degree of displeasure caused by the noise level.This study had several limitations. This study focused on the background noise in a restaurant, and crucial factors in the success of a restaurant such as the quality of food, the service, the interior design were not considered. Music and other conversations mix together to create a sense of privacy within one’s own table. However, when the noise is higher than the level needed to guaranty a certain level of privacy, it can cause a breakdown in communication. In a dining atmosphere, traditionally there are several other patrons enjoying the same atmosphere within relatively close distance of each other, but in this experimental setting, only one table was present in the laboratory. This means that the participants were not considering at all their privacy. A second limitation is that the HATS does not show any visual facial expressions or move its lips. Subconsciously, humans look at another talker’s lips which helps to enhance the auditory signal; however, for those with a hearing impairment could cause them to rely more on lip reading as a compensatory strategy. Moreover, the HATS speech level did not increase with the background noise level, as naturally would happenWith protocol approval of the University of Illinois Urbana-Champaign’s Office for the Protection of Research Subjects Review Board (IRB No. 19479), a total of 31 individuals were recruited for the study. The experiment was performed in accordance with the guidelines and regulations suggested by the University of Illinois Urbana-Champaign’s Office for the Protection of Research Subjects Review Board. Inclusion criteria required the participant to be over the age of sixty years and have normal hearing (<25 dB HL) or hearing loss (> 25 dB HL); additionally, participants must be proficient English speakers, since the intelligibility test will be given in English and non smokers. The participants signed an informed consent form, completed a demographics form, and underwent a hearing test prior to completion of the experiment. The hearing test included otoscopy, tympanometry, speech reception thresholds, and air and bone conduction audiometry. An initial exclusion criterion, in order to continue with the Lombard Effect part of the study, involved pure tone air conduction results showing asymmetries greater than 10 dB HL, at two or more consecutive frequencies, or an air-bone gap greater than 15 dB HL, without a previous medical consultation with an otolaryngologist. Among the 31 participants , 10 were with Normal Hearing, 10 with Mild HL, and 11 with Moderate-Severe HL.After participants confirmed their age, a hearing screening was performed, including reviewed their hearing history, otoscopy, tympanometry, air conduction pure-tone audiometry with insert phones from 250–8000 Hz (with inter-octaves as necessary), speech reception thresholds in quiet, and unmasked or masked bone conduction pure-tone thresholds. Supra-aural headphones were used to reconfirm pure tone air conduction gaps of 10 dB HL or greater between ears at two or more consecutive frequencies.After completion of the hearing test, the individual continued with the second part of the experiment. This included in order the Lombard Effect testing, speech-in-noise intelligibility testing, and scored on a visual analogue scale their perceptual responses of (1) communication disturbance, (2) willingness to spend time, and (3) willingness to spend money in a restaurant. Participants completed all components of the study in one or two forty-five to sixty-minute sessions, resulting from scheduling conflicts and/or participant fatigue.39 and Clark40 degrees of hearing loss.After the hearing evaluation, participants were grouped in three categories. These categories were determined by the collective pure-tone averages of 2000 Hz, 4000 Hz, and 8000 Hz of both ears per participant. Average audiometric thresholds of the right and left ear per participant categories are represented in Figure The Lombard Effect Participants were fit with the head-mounted microphone connected to a portable recorder. Then, participants were asked to read in the presence of pre-recorded restaurant noise the first six sentences of “The Rainbow Passage”22, which is used by Speech Language Pathologists to assess and monitor voice and articulation disorders. The pre-recorded restaurant noise included patrons babble from a real restaurant and the clinking of dining ware and cutlery. The noise was presented at eleven levels from 35 dB(A) to 85 dB(A) with 5 dB interval in a random order. Participants were instructed, by the undergraduate student assistant, with the following: “Each time, I [the listener] would like you to pretend that we are talking in a restaurant and you are telling the story to me. Make sure that I understand you equally well each time.”Speech Intelligibility in Noise The participants completed a speech-in-noise intelligibility test for each of the eleven, randomized noise conditions. Our intelligibility test was designed using the 250–300 standardized Northwestern University 6, NU-641, words available to all audiologists. These words were recorded using the voice of an undergraduate student assistant; the words were individually clipped and then randomized into eleven, twenty-word lists. These recordings were then played through a Head and Torso Simulator (HATS) , placed at one-meter distance from the participant, to guarantee consistency in the speech material. The word lists were presented at a level of 60 dB(A), corresponding to a normal vocal effort at one meter of distance42. Participants were asked to repeat the word pronounced by the HATS. Intelligibility scores were measured as percentage of words correct.Disturbance, Time, and Budget Scores Self-reported communication disturbance and willingness to spend time and money were measured on visual analog scales on paper. The participant was instructed to place a vertical tick on the horizontal line regarding their amount of disturbance, time, and money per noise condition. The paper document was then scanned and uploaded to be measured, in centimeters, using Adobe Acrobat Pro DC Software and the Adobe Software Measurement Tool . The responses were then recorded in an Excel spreadsheet according to the participant’s identification number.43. Each of the eleven “Rainbow Passage” segments were saved according to the participants identification number and noise level condition. MATLAB (R2017a) was used for speech signal analysis. In each condition, the equivalent SPL was measured. For each condition, the mean value of the SPL was obtained per subject. For each subject, the average of SPL among the conditions was computed and subtracted from each mean SPL values for that subject (termed Delta SPL). This within-subject centering was performed in order to evaluate the variation in the subject’s vocal behavior in the different noise conditions from their typical vocal behavior . Each participant was identified by their identification number, gender, age and type of hearing loss. As a first preliminary assessment of the reliability of the recordings, the Voice to Noise Ratio (VNR) was evaluated. To evaluate VNR, mixture of Gaussians models was used. In statistics, a mixture model is a probabilistic model for representing the presence of subpopulations within an overall population, without requiring that an observed data set should identify the sub-population to which an individual observation belongs. In our case, the time history of all the SPL recorded by the microphone represents the overall population. The two subpopulations are the Voice levels and the Noise levels. The distribution of the overall population was modeled as the sum of two Gaussian distributions, where two average values represented the Voice and the Noise average levels. The average VNR among the different noise conditions was 21.2 dB with a standard deviation of 2.0 dB. In the worst case (VNR = 19.3 dB), the contribution of the background noise on the overall level (noise and voice) was about 0.05 dB. This result confirms that the effect of noise on the equivalent level was acoustically negligible.The audio recordings of participants were segmented using ELAN software 44. Reverberation time was measured in the sound booth from the impulse responses (IRs) generated by balloon pops45. The four IRs were recorded in two source positions and two microphone positions by means of an NTI Measurements microphone M2211 (Class 1 frequency response) and analyzed in one-third octave bands by means of an NTI XL2 Audio and Acoustic Analyzer. The reverberation time (T20) at mid-frequencies in the room was 0.05 s, while the background noise was 22.5 dB(A). The hearing test will be performed using a calibrated tympanometer , audiometer , insert phones (3M E-A-RTONE 5A 410-5002), TDH-50 headphones, and bone oscillator. The participants’ speech will be recorded using a head-mounted microphone  and connected to an audio interface . The same restaurant noise was emitted by two directional speakers  placed at 45 to the sides of the participants.The study was performed in a standardized sound-attenuated booth


Adaptive dynamic range optimization (ADRO) is a hearing aid fitting rationale which involves adjusting the gains in a number of frequency bands by using a series of rules. The rules reflect the comparison of the estimated percentile occurrences of the sound levels with the audibility and comfort hearing levels of a person suffering from hearing loss. In the study reported in this paper, a previously developed machine learning method was utilized to personalize the ADRO fitting in order to provide an improved hearing experience as compared to the standard ADRO hearing aid fitting. The personalization was carried out based on the user preference model within the framework of maximum likelihood inverse reinforcement learning. The testing of ten subjects with hearing loss was conducted, which indicated that the personalized ADRO was preferred over the standard ADRO on average by about 10 times. Furthermore, a word recognition experiment was conducted, which showed that the personalized ADRO had no adverse impact on speech understanding as compared to the standard ADRO. Humans have a dynamic range of hearing of about 120 dB sound pressure levels (SPLs). People suffering from hearing loss have a reduced dynamic range of hearing compared to those with normal hearing. Compression is the mechanism by which a reduced dynamic range of hearing is mapped to create the normal dynamic range of hearing during the process of hearing aid fitting [The conventional hearing aid fitting process consists of obtaining a person’s pure-tone hearing thresholds and applying a prescriptive compression or amplification rationale derived from the average values of hearing aid users with similar levels of hearing loss. This process essentially involves applying gain values across a number of frequency bands, depending on the input level of the sound signals. The target gains in the conventional compression or amplification rationales reflect an “average” user and do not take into consideration that different individuals encounter different audio environments and that their hearing preferences in those environments may not be the same.In order to increase the satisfaction level with hearing aids, some ad hoc self-tuning approaches have been reported in the literature ,4,5,6. IIn the study reported in this paper, the previously developed online personalization method of MLIRL was applied to a different prescriptive amplification or hearing aid fitting rationale named adaptive dynamic range optimization (ADRO) ,17,18,19The rest of the paper is organized as follows. In The gain computation module is depicted in Gain values are adjusted by the comparator according to the following rules: (1) if a high percentile estimate  exceeds the loudness discomfort level, then the gain value is reduced, for example by 3 dB/s, as specified in ; (2) if Using the ADRO rules, the gain increase is determined by comparing the 70th percentile and the comfort target. The comfort target has a significant impact on the outcome of ADRO and thus on a subject’s hearing experience. It is worth emphasizing that the comfort target varies from person to person, and it is the parameter personalized in this work. The personalization of the comfort target enables hearing improvement compared to the standard ADRO. In the next section, an overview of the MLIRL personalization applied to the comfort target is described.The details of the developed MLIRL personalization are discussed in our previous work, in . In thisReinforcement learning (RL) is a machine learning method for pursuing the maximum value of a reward function during its training phase. For many problems, the reward function cannot be easily determined. Inverse reinforcement learning (IRL) enables the obtaining of the reward function based on feedback from a human subject. In the IRL framework, a new action is adopted based on the subject’s response to a personalization state.The state and action in our case correspond to the comfort targets in a number of frequency bands, denoted by the sets standard(1), CTstandard(2), …, CTstandard(n)) represent the standard CTs in the n frequency bands. To personalize ADRO, a state/action space is generated by multiplying a scale with the CT in each frequency band as follows:Let  dataset . One lisThis paper presented the personalization of a hearing aid fitting rationale based on adaptive dynamic range optimization (ADRO). A previously developed personalization method based on maximum likelihood inverse reinforcement learning (MLIRL) was utilized to personalize the ADRO. This was achieved by personalizing the comfort target levels across five frequency bands via an online training session. To demonstrate the engineering feasibility or proof-of-concept of this personalization method, subject testing experiments were conducted on ten participating subjects. The results obtained indicated that the personalized ADRO was preferred over the standard ADRO on average by about 10 times. Furthermore, it was shown that the personalized ADRO had no adverse impact on speech understanding as compared to the standard ADRO. The online training feature of the developed personalization method allows it to be easily deployed in the field. In our future work, we plan to carry out this personalization online training in the field or in real-world audio environments by developing a smartphone app.


Atopic dermatitis (AD) is common in children and the majority of children can be treated by the general practitioner (GP). Various factors can influence the GP's treatment strategy and may lead to less effective treatment. The objective is to gain insight into the treatment goal, treatment strategy, explanation and advice given by GPs when dealing with AD in children and to explore which factors play a role in the choice of pharmacological treatment.Semi‐structured interviews in primary care in the Netherlands were audio‐recorded and transcribed. All data were analysed according to the six‐steps approach of inductive thematic analysis.We interviewed 16 GPs. Treatment goals mainly focussed on the short term. GPs discussed the importance of emollient use and emphasised emollients as the basis of treatment. We found that several factors played a role in prescribing topical corticosteroids (TCS); severity of the AD, age of the child, skin type, corticophobia among parents and GPs, experience of side effects and dermatological experience. GPs reported giving limited advice about the use of TCS and prescribed medication that is not recommended by the guideline.Various factors seem to influence GPs' treatment strategy for AD in children. More attention and education about the use and safety of TCS in children during GP training, continuous medical education, probably improve treatment in line with guidelines and can lead to more confidence and knowledge about TCS among GPs, which ultimately may improve the education and self‐management of patients.  The prevalence of doctor diagnosed AD in children was reviewed by Bylund et al. and ranged from 1.8% to 22.6%.The cornerstone of all AD treatment is emollients, usually in combination with TCS. Guidelines may differ, especially between primary and secondary care, regarding treatment strategies with TCS for paediatric AD. The Italian guideline advise starting with high‐potency TCS when AD flares up.Despite the presence of national and international guidelines, many children with AD are underusing topical treatments and suffer more from their eczema than necessary,In order to improve the treatment of AD in children, it is crucial to know how GPs manage AD and to understand their beliefs in relation to their medical treatment strategy. This qualitative study aims to explore what the treatment goal is and what information GPs provide to parents of children with AD. Furthermore, we want to examine what recommendations are given about emollients, bathing and other treatments in daily practice. Finally, we want to explore which factors play a role in the decision whether to prescribe TCS for treatment of AD in children. What information is provided to parents, and when do GPs consider prescribing a potent TCS?33.1The study was carried out among GPs in two regions in the southern and western parts of the Netherlands. Through an informative email 140 GPs were approached, in total 20 GPs responded positively. We used purposive sampling based on years of experience, prior dermatological experience was taken into account, including general working experience in dermatology and a dermatology internship during the GP training. In addition, GPs were asked whether they had been diagnosed with AD themselves and/or had a relative with AD.3.2All GPs received written information and provided written informed consent. Data were analysed and stored anonymously. The study was approved by the Medical Ethics committee of the Erasmus Medical Center, Rotterdam (MEC‐2019‐0626).3.3Interviews were semi‐structured with open‐ended questions. We prepared a list of topics and composed questions based on the aims of the study and the available research literature, see Appendix Data were collected in September and October 2019. The interviews took place in the Erasmus MC or in the GP practices and lasted between 15 and 40 min. Each interview was conducted by one researcher , and a second researcher  attended the interview. Tessa Warendorff was a master student and conducted interviews as a part of her master thesis, she was supervised during the interviews by Karlijn F. van Halewijn when Tessa Warendorff was the first interviewer. The interviews were audio recorded, anonymised, transcribed verbatim (Tessa Warendorff) and checked by a second researcher .3.4We used inductive Thematic Analysis to analyse all transcripts, using the six analytic steps described by Braun and Clark.3.5Maximum variation in the data sample was achieved by including GPs with different numbers of years of experience, different practice locations and varying levels of dermatology experience. Diversity of perspectives in the research team was achieved by involving researchers from different backgrounds, that is, general practice , dermatology (Suzanne G. M. A. Pasmans) and communication and psychology (Mario Veen).44.14.1.1In total 16 GPs were interviewed. Ten GPs were female (62.5%) and the years of experience as a GP ranged from 3 months to 38 years. There were four GPs with prior dermatological experience, two GPs had been diagnosed with AD or had had AD as a child and five GPs had a child with AD.4.1.2GPs reported that their main short‐term treatment goal was to get the children symptom‐free with no more itching or pain and restore disturbed sleep. Furthermore, they named fewer exacerbations and adequate self‐management as treatment goals.4.1.3Quote 1 (GP 6):GP: “Well, then you explain that it can take a long time to go away and it’s something you have that can flare up from time to time and that it can also disappear for a while and, um… well, that it requires a lot of attention from the parents to treat it properly.”When explaining the course of AD, GPs generally emphasised the chronic character of AD and the fact that it flares up. On the other hand, they offered the perspective that in most children AD can improve and disappear as they grow older. GPs stressed that treating AD requires a lot of attention from the parents.4.1.4Quote 2 (GP 9):And then I always start by telling them that the basis for eczema treatment is to keep the skin greasy. And I explain that dry skin is much more likely to get eczema patches, so keeping the skin a bit greasy is the key thing.GPs highlighted the use of emollients as the basis of treatment and they mentioned that the emollients should be used generously and as frequently as necessary. This in concordance with the Dutch GP‐guideline.It was stated GPs indicated that they preferred ointment in the case of a very dry skin and cream in the case of oozing skin. Other GPs reported general preference concerning ointment or cream. Some GPs reported prescribing an ointment because it is the best choice because of the dry skin in AD, and it is more user‐friendly as it will stick to the skin. Other GPs reported to prescribe a cream because it spreads better and absorbs faster. Some had positive experience with using emollients for themselves or relatives, which influenced their prescription behaviour.The advice to use emollients at least twice a day and more if needed was given by all GPs. Only one GP mentioned covering the whole body with emollients. None of the GPs gave advice about the amount of emollient to use.GPs reported giving advice about bathing, showering and the use of soap in line with the Dutch GP guideline for AD. This recommends short (target time 5 min), lukewarm (37°C) and infrequent bathing/showering  and use of only a little soap.www.thuisarts.nl) specifically designed for patients and containing reliable information provided by the Dutch College of General Practitioners (NHG).It was remarked GPs referred patients to a certain Dutch website :Interviewer: “OK, so the basis is the emollients. But given that they’ve often already been using that or are already familiar with it, you often start straight away with a corticosteroid, right?” GP: “Yes, yes. And if they… I prefer not to do that with really young children, so I don’t like to do it if they’re younger than four. Um… what I do then is I often refer them to the dermatologist to perhaps start with tacrolimus.”As expected, the severity and the number of symptoms played an important role for all GPs in whether they prescribed TCS and what kind of TCS they prescribed. Severity of AD was one factor. If the AD was more severe, all GPs were tempted to start directly with a low‐potency TCS in addition to the emollients or to even to start with a more potent TCS. The age of the child was another factor taken into account when prescribing TCS. One GP indicated never prescribing a TCS for children under the age of four.Another GP said they never prescribed a potent TCS to children under the age of 10 because they felt it was never necessary. However, one GP always started with a very potent TCS no matter how old the child was. Other GPs expressed not wanting to prescribe a potent TCS or higher to young children.Quote 4 (GP 13):GP: “In the past, I always used mild TCS. But since, um… [professor of child dermatology] has been working here in the outpatient clinic and he goes for a brief treatment and a very potent TCS. So it’s a very potent TCS from the start.”Interviewer: “Right, so you do that too…?” GP: “Yes.” Interviewer: “Right, so do you do that with all children, or…?” GP: “I do that with all children as a rule.” Interviewer: “With all children, OK. So the age or whatever doesn’t matter…?”GP: “No.”The Dutch GP‐guideline suggests to base the potency of TCS on the severity of the AD, the effect and the frequency of exacerbations and take into account the patient's previous experience. Furthermore, a potent TCS for children under the age of 2 years is suggested for short‐term only when AD is severe.4.2.2Quote 5 (GP 5):Interviewer: “Does parental anxiety still play a role? So you start with, um…”GP: “[…] No… well, sometimes it does of course if it’s quite a severe case. So, um, um… then I might move on more quickly to a slightly tougher treatment. If they’re applying a TCS anyway, it’s often not that clear for the parents whether it’s a mild, moderate or potent. That’s to persuade them that it genuinely works.”It was stated that GPs still notice concerns about the use of TCS among parents. In most cases an extended explanation could reassure parents. However, to reduce corticophobia, two GPs occasionally started with a more potent TCS to get a rapid response and convince worried parents about the efficacy of TCS.On the other hand, some of the GPs reported postponing a treatment with TCS or not prescribing TCS as a result of fear among parents.4.2.3Quote 6 (GP 8):GP: “I think that I, um… well, look, it all depends to a certain extent but if it’s not that severe I just start with hydrocortisone butyrate, so that’s a moderate TCS. But if it’s really severe then I’m quite happy to give Dermovate (very potent TCS) for a few days, yes.”Years of experience as a GP seemed to play a role in prescribing TCS. Seven out of eight GPs with more than 20 years of experience prescribed TCS to children when they believed it was necessary, without any doubts.Quote 7 (GP 3):Interviewer: “If you, um… so don't get a result with a moderate TCS, then you're saying that on rare occasions you will prescribe a potent TCS…””GP: “Well, I’d have to look at the case more closely…”Interviewer: “OK, so it’s not something that is in your protocol?”GP: “No. If that’s the case I’m looking at then I would definitely have to have a good look at the guideline and see right, that’s where I am now, what does the eczema look like, right. I don’t think I’ve ever… if I had to consider that, I’d be thinking what should I do, should I refer them or continue applying the ointment or… well, then I just would have to investigate things a bit further.”In contrast, the younger GPs with less than 5 years of experience seemed more cautious in prescribing TCS to children; they hardly ever prescribed a potent TCS.Quote 8 (GP 11):GP: “Well for a long time, when we were training and even before that, they always said hormone cream is really bad for you. That your skin will get thinner every time you apply it. Um… you know and that at some point you skin will get damaged, and that it will never recover. [..] Um.. so that’s kind of funny because in the back of my mind I still hear my professor saying that in lectures and you think, oh right shoot.”Furthermore, GPs claimed they had no fears about TCS, some were reluctant to prescribe a (potent) TCS, especially in younger children. Eventually it was mentioned that this cautiousness was taught during their medical and GP training, some said that they were afraid of side effects and or that they have limited experience with potent TCS in children. It was stated that GPs had observed side effects from TCS, also in children, which all developed after uncontrolled long‐term use. Hypopigmentation, stretch marks, skin thinning and telangiectasia were named side effects by the GPs.4.2.4Quote 9 (GP 9):GP: “So I think yes, the advice the pharmacy gives also has big consequences for how people deal with it. I mean, it’s all very well me telling them you should just apply those corticosteroids but if the pharmacist’s assistant then tells them to watch out because it’ll make the skin thinner, well they will simply forget what I told them.”Divergent advice about TCS given by a dispensing pharmacist (or assistant) interfered with the advice of the GP and this reinforced the concerns of patients and parents. Overall, this may lead to poor adherence.Additionally, the reimbursement of healthcare insurances can affect a GP's choice of treatment. A few GPs mentioned that in some cases they had to prescribe other emollients or TCS because the one preferred by them was no longer covered by the insurance.4.3Quote 10 (GP 14):GP: “In terms of duration, I generally say um… for the, um… mild TCS, no longer than a week and after that it should definitely not be continued for a few days. Um… and for the moderate TCS and stronger, um… I usually go for five days.”The recommended duration of TCS treatment varied among the GPs from a maximum of 5 days to a duration of up to 4 weeks. The rationale behind the recommended maximum duration varied between minimising the risks of side effects and the need to step up therapy when there is no effect. The Dutch GP‐guideline recommends to evaluate the effect of the treatment in one to 2 weeks and recommends to limit daily use of potent TCS till 2–3 weeks due to the risk of local side effects.Furthermore, the recommendation to apply the TCS thinly was explained by some GPs. The fingertip unit as an indication for the use of TCS and recommend by the Dutch GP‐guideline was not reported by the GPs. The majority of the GPs reported advising apply TCS twice a day, which is in line with the current Dutch GP‐guideline. A few told to apply TCS a maximum of once a day on delicate skin for example, eyelids.4.4In general, it was remarked that GPs did not have difficulties with starting with a potent TCS in children. However, it is stated that only a potent TCS is prescribed in children above a certain age and/or only in certain areas (i.e. elbows and knees) and in the case of severe AD. Furthermore, overtreatment with TCS and reduced use of emollients were mentioned as a counterargument for not prescribing a potent TCS. It was remarked GPs were concerned patients would use a potent TCS for too long with side effects as a result. GPs also mentioned mild and moderate TCS to be sufficient and said there was no need to prescribe a potent TCS.Quote 11 (GP 11):GP: “So I have no problem with the step‐down approach but it shouldn’t be um… a sort of easy way out, like we say oh, we don’t feel like putting a lot of time into it so we’ll just slap on these kill or cure remedies you know, because in particular with Vaseline if you apply it properly then in many cases of eczema you’re actually fine. So it’s a bit sort of, I’m not against it but I feel you should also continue to consider and assess things carefully, you know.”It was stated GPs said they occasionally prescribed a potent TCS as the initial therapy in children and had positive experiences with this treatment strategy.55.1The semi‐structured interviews with GPs in the Netherlands explored the treatment goals, explanations and advice given by GPs about AD in children. Our study revealed multiple factors that play a role in prescribing TCS in children with AD, and that different GPs have different approaches to prescribing potent TCS in children with AD.GPs said the treatment goal with respect to the disease is mostly focussed on the short term to get the child free of symptoms and itching. About the explanation of the condition, the GPs reported to be more focussed more on the chronic character and the fact that it flares up. GPs told they give advice about the importance of emollients and frequency of use, but not on the amount needed for effective use.We found that several factors played a role in prescribing TCS. These factors can be categorised into patient, parent, GP, pharmacy and economic factors Figure . All of 5.2As far as we know, this is the first qualitative study to explore what GPs explain and advise about childhood eczema, and which factors influence the GPs' treatment strategy. In contrast to quantitative studies, this qualitative study enabled us to determine why GPs made specific decisions in their management of AD in children.An adequate sample size was realised as saturation was achieved for the main themes and subthemes. The study was carried out among GPs from two regions in the southern and western part of the Netherlands. This is a wide area with urban and rural settings, and generalisability to other parts of the country is not expected to be a relevant limitation. A limitation of this study is that we do not know if what the GPs say they do is what they actually do in practice. On the other hand, the GPs said this was what they actually do in practice and their answers were not always in line with the Dutch GP guideline, so they were not just giving socially desirable answers.The first few interviews were conducted by one researcher, who is a GP trainee , while all other interviews by a second researcher (Tessa Warendorff) who was finishing her Master's degree in medicine. Research shows that respondents' perceptions of the interviewer can influence the interview interactions.5.3The treatment goal of the GPs was mostly focussed on the short term (relieving symptoms) or educating the patients in adequate self‐management. However, the treatment goal in the Dutch GP guideline is complete remission of the AD.Santer et al. found that parents who received more information about AD and explanation of the rationale for prescribing an emollient appeared more convinced of the need for long‐term emollient use to prevent flare‐up.We did find that the GPs emphasised the chronic character to the patients, but on the other hand they offered the perspective that in most children AD can improve and disappear as they grow older. The discrepancy between a chronic condition in childhood and automatic recovery as they grow older is difficult to understand for parents/patients and may lead to confusion about the course of AD and the treatment strategy. Taesdale et al. found treatment adherence could be supported by stressing that AD is a long‐term episodic condition.It is notable that GPs prescribe medication that is not recommended by the guideline such as very potent TCS and tacrolimus. In the case of antihistamines, evidence that they reduce itching is lacking.Our results regarding prescribing TCS are partially in line with previous studies, which have found that GPs experience uncertainty about prescription quantities and the use of potent TCS for children and adopt trial‐and‐error approaches to emollient use.Farrugia et al. found that there is a need for re‐education of pharmacists and GPs on the safety of TCS use and the potential impact of their counselling of patients and parents on treatment adherence.Re‐education may also be needed for Dutch GPs and pharmacist (assistants) to give them more background information on prescribing TCS when needed for the treatment of AD in children. This is desirable not just for GPs who are afraid of using strong TCS in children but also for GPs who prescribe a very potent TCS in every case.5.4GPs should put more emphasis on the long‐term goal in the treatment of AD. The focus seems to be too much on the short‐term relief of symptoms. Parents and children benefit from a clear explanation of the chronic character of the condition, and its possible disappearance with age should be explained cautiously. More attention and education about the use and safety of TCS in children during the GP training, continuous medical education, and a better implementation of the guideline may improve the consistency among GPs in their advice and prescribing of TCS. Pharmacists (assistants) should not be forgotten in the education about the use and safety of TCS in children. More knowledge and consistent information spread by the primary care team about the correct use of TCS can lead to better education of patients and/or parents, which may lead to better self‐management in children with AD.Karlijn F. van Halewijn: Conceptualization ; Data curation ; Formal analysis ; Methodology ; Project administration ; Writing – original draft ; Writing – review & editing . Tessa Warendorff: Data curation ; Formal analysis ; Writing – original draft . Arthur M. Bohnen: Conceptualization ; Methodology ; Writing – review & editing . Mario Veen: Methodology ; Supervision ; Writing – review & editing . Suzanne G. M. A. Pasmans: Conceptualization ; Writing – review & editing . Patrick J. E. Bindels: Conceptualization ; Writing – review & editing . Gijs Elshout: Conceptualization ; Formal analysis ; Investigation ; Methodology ; Writing – original draft ; Writing – review & editing .All authors state no conflicts of interest for this article.All GPs received written information and provided written informed consent. Data were analysed and stored anonymously. The study was approved by the Medical Ethics committee of the Erasmus Medical Center, Rotterdam (MEC‐2019‐0626).Supporting Information S1Click here for additional data file.Supporting Information S2Click here for additional data file.


Effect of gut microbiota on colorectal cancer progression and treatmentAlasiri discusses an in depth role of gut microbiota and its functions to explore the link between development of colorectal cancer (CRC) in patients and their responses to treatment. Several studies have shown that gut microbiota can induce resistance against pathogens and regulate the immune system. Colorectal cancer is the third-deadliest cancer worldwide, accounting for approximately 900,000 deaths per year globally. Gut microbiota has been heavily linked to CRC incidence and prevention via bacterial metabolites, invasion, translocation, host’s defense modulations, and bacterial-immune system interactions. In addition, it can influence the metabolism of chemical compounds such as drugs and xenobiotics to manipulate the treatment response in CRC patients.see page 1289 Investigation of preoxygenation methods in cesarean surgeries with the oxygen reserve index2 at a rate of 10 L.min-1 for 3 min at normal tidal volume (Group 1) and 30 s with the 4 deep vital capacity technique (Group 2). The study was completed with 66 patients. Fraction of inspired oxygen (FiO2) values were found to be low in T1 (p=0.012) in Group 1, and high in fraction of expired (FeO2) values in T1 and T2 (p=0.025 and p=0.009) in Group 2, while no significant differences were found at other times (p>0.05). We obtained greater FiO2 and FeO2 values in preoxygenation with the 30 s 4 deep vital capacity method, and because this method did not cause a significant decrease in the post-intubation ORI values, we believe that the usage of this method in cesarean section surgeries may be appropriate.Kocakulak et al investigate preoxygenation methods that were carried out for 3 minutes (min) at tidal volume and 30 seconds (s) with the 4 deep vital capacity technique using the Oxygen Reserve Index (ORI) among pregnant women. The patients were randomly divided into 2 groups with the provision of preoxygenation using 100% Osee page 1317The role of laparoscopy in emergency colorectal surgeryAlselaim et al assess the outcomes of the laparoscopic approach compared to those of the open approach in emergency colorectal surgery 241 patients  were included in this study. Thee length of stay in the intensive care unit was shorter in the laparoscopic than in the open group (1±3 days verses 7±16 days). After multivariable logistic regression, patients undergoing laparoscopic resection had a 70% lower risk of surgical site infection than those undergoing open surgery , a difference that was not significant. The use of laparoscopy in emergency colorectal surgery is safe and feasible, with a trend toward better outcomes. Colorectal surgery specialization is an independent predictor of an increased likelihood of undergoing laparoscopy in emergency colorectal surgery.see page 1333A nationwide, cross-sectional studyPrevalence of transfusion-transmitted infections in Saudi Arabia blood donors. Alsughayyir et al establish a nationwide epidemiological profile of transfusion-transmittable infection (TTI) markers among seemingly healthy blood donors to update policies required to ensure blood safety. A total of 375,218 whole blood units were donated. Notably, the central and southern regions were the epicenters of TTI-reactive blood donors. Hepatitis B virus (HBV) markers accounted for 85.7% and were the overall most prevalent of TTI-positive donations, followed by hepatitis C virus (HCV) at 5.9% and syphilis at 5.6%. In particular, anti-HBc and hepatitis B surface antigen (HBsAg) were most prevalent in the south, while HBV NAT was highest in the center. Hepatitis B virus, HCV, and syphilis carry the greatest risk of TTI in Saudi Arabia. Including HBsAg screening is a necessary precautious measure to maintain blood safety.see page 1363


Hearing aid use and satisfaction can be used to analyze the effectiveness of hearing rehabilitation, an issue few explored in Brazilian users.Evaluate hearing aid use dispensed in a publicly-funded health service after one year, the interventions needed and users' satisfaction.Prospective observational cross-sectional study. Hearing aid users were invited by telephone to participate in an evaluation of hearing aid use.200 hearing aid users attended the evaluation (47% of sample loss); 76.5% of the subjects were using hearing aids bilaterally, 10.5% unilaterally and 13.0% none of them; 99.5% of users needed some kind of intervention. Users who kept wearing their hearing aids were considered “satisfied”.Active search by telephone showed that hearing aid users who attend this publicly-funded health service have difficulties to attend follow-up appointments. Most of the users that came for evaluation kept using their hearing aids; non-use rate was 13%. Practically all hearing aid users needed some kind of intervention. Despite the high level of satisfaction, those findings did not include users who did not participate in evaluation, which could represent subjects less adhered to the treatment. Results highlighted the need of periodical follow-ups to ensure the effectiveness of auditory rehabilitation. In Brazil, they can be acquired in private hearing aid dispensers or in publicly-funded hearing care services accredited by the Brazilian Public Health Care System  with mild to moderately severe, bilateral and symmetric sensorineural hearing loss, who wore digital behind-the-ear hearing aids with nonlinear amplification in both ears for one year, with no previous experience with hearing aids. Subjects with neurologic disorders, outer or middle ear malformations, manual dexterity problems or fluctuating hearing loss were the exclusion criteria from study sample.All participants signed an informed consent form and underwent an evaluation consisted of six steps, described as follows:Step 1: Initial interviewa.“Do you use your hearing aids? Do you have any problem?”b.“Do you usually wear both hearing aids , only one  or none of them?”c.“What is the main reason for not wearing your hearing aids?”d.“Approximately how many hours per day do you use your hearing aids?”e.“Have you made some kind of follow-up  during this year using your hearing aids?”Participants answered open-set questions regarding hearing aid use:Step 2: SADL™ questionnaireEach subject answered the SADL™ items as an interview with the researcher, which allowed explanations about the doubts according to their difficulties. Considering that all subjects had hearing aids provided by public resources and not purchased, item 14 (“The cost of the hearing aids seems reasonable?”) was used in order to assess satisfaction regarding costs of batteries and maintenance of hearing aids, unlike the original proposalStep 3: Visual inspection of external auditory canal, to verify the presence of earwax blocking the ear canal.Step 4: Pure tone audiometry, to assess possible changes in hearing thresholds that could influence hearing aid fitting.Step 5: Earmold check, to analyze integrity and quality and factors that may cause physical discomfort.Step 6: Hearing aid's sound check with stethoscope, to verify quality of amplification.All orientations and suggested interventions were registered and classified as major or minorData were analyzed using descriptive statistics.Although 376 subjects were initially selected as sample of this study, active search by telephone resulted in 200 participants who attended the evaluation appointments (47% of sample loss).Considering all 200 hearing aids users assessed in this study, 102 (51%) were female and 98 (49%) were male, mean age of 71.3 years. Major education level was uncompleted elementary school (58.5%) and 55.5% were retired.Only 68% of subjects returned for follow-up appointments in the first year, even though all of them were oriented about the importance of follow-ups during fitting process.The analysis of hearing aids use considered three aspects: mode of hearing aid use , reasons for non-use of hearing aids and hours using hearing aids.The analysis of reasons for non-use of hearing aids regarding users who were not using one or none of them is at Regarding to hours of use, the average was 8.6 hours per day, minimum of 0 hours per day and maximum of 18 hours per day; 60.5% reported to wear their hearing aids for eight hours or more and 13% were not wearing them at all.Major interventionsUsers who kept wearing their hearing aids bilaterally or unilaterally answered SADL™ questionnaire. Results were analyzed considering Global Satisfaction and subscales: Positive Effects, Negative Features, Service and Costs and Personal Image, as seen in This study had a descriptive and exploratory design and intended to be a starting point for a discussion about the effectiveness of Brazil's public policies on hearing health, and based in its findings, originate new conclusive studies regarding hearing aid use including users from other places of the country.Initially, 376 subjects were selected for this study according to inclusion and exclusion criteria. However, there was a considerable loss of the sample in active search by telephone, and only 53% of the sample primarily chosen attended the evaluation appointment, totalizing 200 subjects. The reasons for sample loss were: failure to contact by telephone, unattended appointments, failure to schedule appointments by health problems or difficulty to go to publicly-funded health service, returned hearing aids and death. These results will be discussed in an upcoming study, but show that hearing aid users have difficulties to attend follow-up appointments in this publicly-funded health service, which affects long-term effectiveness of auditory rehabilitation.As an important measure to manage and improve the quality of publicly-funded health services and the effectiveness of auditory rehabilitation in Brazil, more studies should be executed in other services in different parts of the country, taking into consideration the existing guidelinesAlthough hearing aid non-use rates vary in literature, the rate of 13% of non-use observed in the present study is higher than 3% seen in an Australian studyAs seen in In cases of unilateral or no use of hearing aids, the subjects were interviewed about the reason to abandon use, choosing only one main argument. As noted in This fact suggests the necessity to improve long-term follow-up system of publicly-funded health services and users' access to follow-ups appointments, since 32% did not make any kind of follow-up in the first year of hearing aid use, differently from what is proposed in guidelines for audiology servicesIn relation to hours of hearing aid use, most of users reported to use hearing aids for at least 8 hours daily and the average of use was 8.6 hours, which suggests hearing aids use during most of daily activities.The average of use seen in this study is lower than the daily average of 9.5 hours found in United StatesPractically all users of this study (99.5%) needed some kind of intervention after one year, and 40.5% had substantial problems with their hearing aids requiring major interventions. This rate was similar to the one found in U.K.According to It is also important to highlight the amount of users that needed “explanation on draining and purchase of batteries” (11.5%), who did not know about the necessity of changing batteries or where to buy them, even after one year of hearing aid use. Some subjects were not using effectively their hearing aids because they did not have financial resources to buy batteries, so they did not wear any hearing aid for some period or used them for few hours to save battery charge.Some users of this study still kept on wearing their hearing aids even with substantial problems for use, like faulty earmolds, faulty hearing aids or drained battery. Many of them were not aware of the necessity of adjustments and maintenance over time, for many “it was enough to use hearing aids just the way they were given”, according some users of this study. This behavior was also seen in other Brazilian hearing aid usersBased on the facts seen in this study, many Brazilian users still have doubts and difficulties in dealing with their hearing aids, even with orientations received during fitting process. Considering that most of users are elderly people, with uncompleted elementary school and poor speech comprehension due to hearing loss, probably the time granted for orientation and counseling is not enough to elucidate all questions they have, which damages use, benefit, satisfaction and even adherence to hearing rehabilitation, as well as its effectiveness over timeAccording to SADL™ analysis, 97.49% of hearing aids users were satisfied and global satisfaction mean score was 6.0 , correspAll scores from SADL™ subscales also represented high level of satisfaction with hearing aidsThe application of question 14 from SADL™ differently from the originalSADL™ questionnaire was chosen for containing direct questions, being focused on clinical application and it has been used to evaluate satisfaction in Brazilian hearing aid users from other publicly-funded audiology services•Active search by telephone showed that hearing aid users who attend a publicly-funded health service have difficulties to attend follow-up appointments.•Most of the users that came for evaluation kept using hearing aids bilaterally (76.5%); non-use rate was 13%.•Practically all users (99.5%) needed some kind of intervention, which emphasize the necessity of periodical follow-ups to ensure long-term effectiveness of hearing rehabilitation.•Considering users who came for evaluation and kept wearing their hearing aids, most of them (98%) were satisfied with amplification according to SADL™ questionnaire. However, this result did not include users who did not come to evaluation appointment, which could represent subjects less adhered to the treatment.