While triclosan (TCS) exerts detrimental effects on female reproduction, the effect of TCS-derived toxins on porcine oocytes during in vitro maturation (IVM) is unclear. This study investigated the effects of TCS on mitochondrion-derived reactive oxygen species (ROS) production and apoptosis pathways during porcine oocyte maturation. Porcine oocytes were treated with TCS  and triphenylphosphonium chloride , and matured cumulus oocyte complexes (COCs) were stained with orcein, dichlorofluorescein diacetate (DCF-DA), and Mito-SOX. Proteins and mRNA levels of factors related to cumulus expansion and mitochondrion-mediated apoptosis and antioxidant enzymes were analyzed by western blotting and reverse-transcription polymerase chain reaction (RT-PCR), respectively. Meiotic maturation and cumulus cell expansion significantly decreased for COCs after TCS treatment along with an increase in mitochondrial superoxide levels at 44 h of IVM. Further, mitochondrion-related antioxidant enzymes and apoptosis markers were significantly elevated in porcine COCs following TCS-mediated oxidative damage. The protective effect of Mito-TEMPO as a specific superoxide scavenger from TCS toxin improved the maturation capacity of porcine COCs. Mito-TEMPO downregulated the mitochondrial apoptosis of TCS-exposed porcine COCs by reducing superoxide level. In conclusion, our data demonstrate that TCS mediates toxicity during porcine oocyte maturation through superoxide production and mitochondrion-mediated apoptosis.  Previouw/w) . Althougw/w) , its impTrissolcus japonicas [Eisenia fetida [TCS-mediated production of reactive oxygen species (ROS) causes oxidative stress and may lead to DNA damage. TCS was found to induce oxidative stress and genotoxic response in goldfish , was assaponicas . Furthera fetida . In parta fetida . These ra fetida ,11,12,13Bisphenol A (BPA) and TCS are endocrine-disrupting chemicals with structural similarity to 17β-estradiol, an estrogen hormone . BPA is To investigate the oxidative stress and superoxide production upon exposure to TCS, we evaluated meiotic maturation of porcine oocyte and cumulus cell expansion of porcine COCs after 44 h of in vitro maturation (IVM). We confirmed the changes in intracellular ROS and mitochondrion-derived superoxide production in porcine COCs during IVM following TCS exposure. In addition, we determined the protective effects of triphenylphosphonium chloride (Mito-TEMPO), a specific superoxide scavenger, against TCS-induced superoxide production by evaluating alterations in mitochondrion-related antioxidant enzymes and apoptosis of porcine COCs.p < 0.001) following exposure to 100 µM TCS as compared with that reported for non-treated matured COCs. mRNA levels of the factors related to cumulus cell expansion  were significantly lower in porcine-matured COCs treated with 10 and 100 µM TCS . Thus, TCS exposure affected the in vitro meiotic maturation of porcine oocytes. These results indicate that exposure to TCS results in the inhibition of cumulus cell expansion in a TCS concentration-dependent manner.We first examined the effect of three different concentrations of TCS  on porcine oocyte maturation after 44 h of IVM. The changes in meiotic maturation were observed by staining of porcine oocytes with orcein c,d. Meiop < 0.05 for 10 and 100 µM TCS groups versus non-treated group; p < 0.05) for 100 µM TCS-treated porcine COCs than that reported for other groups  in porcine COCs after TCS treatment  in porcine COCs treated with 100 μM TCS than in those from other groups. Thus, porcine COCs exposed to TCS showed an increase in intracellular ROS and mitochondrial superoxide production after 44 h of IVM.We investigated intracellular ROS and mitochondrial superoxide levels in porcine COCs using dichlorofluorescein diacetate  and Mito-SOX (red fluorescence) staining after treatment with TCS  during IVM. The green fluorescence corresponding to intracellular ROS level significantly increased in a TCS concentration-dependent manner , Cyto C, cleaved Caspase-3, and cleaved Parp1) in TCS-treated COCs. A significant increase of Bax and Caspase-3 mRNA expression was found at 100 µM TCS for 44 h of IVM  in 100 µM TCS group. Based on the results above, we selected 100 µM TCS as the exposure level for the subsequent experiment.Previous study demonstrated that the activation of apoptosis from mitochondria is associated with generation of ROS and superoxide . We perfh of IVM a. As shop < 0.001; 0.1 μM Mito-TEMPO group, 76.2% ± 9.7%; TCS + Mito-TEMPO group, 63.8% ± 1.3%; nonsignificant difference). The reduction in cumulus expansion following TCS treatment was also rescued after exposure to 0.1 µM Mito-TEMPO  as a superoxide scavenger against BPA-induced ROS, as evident from the improvement in oocyte maturation and blastocyst development in pigs ,18. To ep < 0.05)   following TCS pretreatment showed significant amelioration in intracellular ROS and superoxide production ( < 0.05) a,b. In c< 0.001) c. These Bax following Mito-TEMPO treatment (TCS + Mito-TEMPO) significantly reduced  in porcine COCs. Mito-TEMPO treatment significantly increased (p < 0.01) the mRNA expression of Bcl-xl (caspase-3 significantly decreased (p < 0.01) in the Mito-TEMPO-treated group as compared with that observed in only TCS-treated group. As expected, the protein levels of mitochondrion-mediated apoptosis factors AIF and Cyto C increased in porcine COCs exposed to TCS, and these levels were significantly restored  after Mito-TEMPO treatment. Western blotting data revealed that the increased levels of cleaved caspase-3 and cleaved PARP1 in TCS-treated COCs were dramatically downregulated (p < 0.001) by Mito-TEMPO treatment during IVM II. Thus, the increase in mitochondrion-mediated apoptosis following TCS-induced damage was ameliorated by Mito-TEMPO during the IVM of porcine oocytes.To confirm the protective effect of Mito-TEMPO against TCS-mediated damage, porcine COCs were exposed to 0.1 µM Mito-TEMPO after TCS pretreatment and the activities of mitochondrion-derived apoptosis pathways were determined by RT-PCR and western blot analyses. As shown in f Bcl-xl a. Furthe2−) production. We found that the treatment of porcine COCs with a relatively high concentration of TCS (100 μM) resulted in a significant decrease in meiotic maturation and cumulus cell expansion  and may induce oxidative stress in rat thymocytes [Sod2, Prdx3, and Prdx5) and Mito-SOX staining intensity increased following treatment of porcine COCs with TCS during IVM. These results indicate that TCS may disrupt the mitochondrion-related antioxidant system during porcine oocyte maturation.The enzymatic antioxidant system plays a crucial role in the elimination of ROS to maintain the balance between its production and removal . In addiymocytes . As one ymocytes . The mitymocytes . In the We observed an increase in the mitochondrial apoptosis rate via superoxide production in TCS-exposed porcine COCs . The detMito-TEMPO is a specific mitochondrial superoxide scavenger that mimics the activity of superoxide dismutase . Our prein vitro fertilization (IVF) has not been investigated. Our results provide valuable information that porcine oocyte maturation during IVM was adversely affected with TCS exposure via the mitochondrial superoxide production. However, in the study, the Triclosan concentration of 100 uM was never physiologically observed in the body, although to date, there are insufficient reports of detection of TCS in female reproduction system such as ovaries, uterus, and vagina. The present study demonstrates that TCS exposure exerts a negative impact on the meiotic maturation and cumulus expansion of porcine COCs during IVM and alters mitochondrial superoxide-induced apoptosis activity , unless otherwise stated.w/v) supplemented with 75 μg/mL potassium penicillin G at around 30–35 °C. Immature COCs were aspirated from follicles (3–6 mm in diameter) using a 10-mL syringe and an 18-gauge needle. The undamaged COCs with similar quality of cytoplasm and surrounding cumulus cells were selected by mouth pipetting and washed thrice with Tyrode’s lactate-N-2-hydroxyethylpiperazine-N′-2-ethanesulfonic acid (TL-HEPES) medium. Immature COCs were selected under an optical microscope, as previously described [2. North Carolina State University-23 (NCSU-23) medium supplemented with 10% follicular fluid (v/v), 0.57 mM cysteine, 10 ng/mL β-mercaptoethanol, 10 ng/mL epidermal growth factor, 10 IU/mL pregnant mare’s serum gonadotropin (PMSG), and 10 IU/mL human chorionic gonadotropin (hCG) was used for oocyte maturation. After cultivation for 22 h (IVM I), the oocytes were matured in the same medium without PMSG/hCG for 22 to 44 h (IVM II). TCS was prepared in dimethyl sulfoxide (DMSO). During maturation, the cells were exposed to TCS  added to the maturation medium NCSU-23 for 44 h as previously described [Porcine ovaries were obtained from 6-month-old female pigs (Yorkshire/Landrace (♀) × Duroc (♂), 100 kg) from local abattoirs (Gyeongsan and Daegu City) and transported to the laboratory in 0.9% saline (escribed . Approxiv/v) and then stained with 1% acetic-orcein (v/v) for 5 min. Meiotic stages of samples were investigated under a microscope .Cumulus expansion in porcine COCs was evaluated under a microscope  after 44 h of IVM in the presence or absence of TCS and Mito-TEMPO. The process was divided into three steps as previously described ,36. Afte® RT-PCR Premix . Specific primers for the sequences of interest  according to the manufacturer’s instructions. RNA concentration and purity were measured using OPTIZEN NanoQ , and 1 µg/µL of total RNA was used to synthesize cDNA using AccuPowerinterest  were des2. Following incubation, the COCs were washed thrice with 0.1% PVA-PBS, and their fluorescence was recorded using an Olympus DP 70 camera . Mito-SOX (red)-stained cytoplasm was examined using the iRiS™ Digital Cell Image System . Porcine COCs were washed thrice in PBS-PVA and cultured in 300 μL of IVM II medium mixed with Mito-SOX  at 37 °C for 30 min. The COCs were then fixed with 2.5% glutaraldehyde/PBS (v/v) for 1 h and permeabilized with 0.1% Triton X-100 (v/v) for 30 min, followed by staining with Hoechst 33342 (2 mg/mL). The COCs were covered with a cover glass after mounting on glass slides using a mounting solution.The levels of intracellular ROS in porcine COCs were measured using the DCF-DA method , as previously described . After wMatured COCs (30 per sample) were lysed using PRO-PREP protein lysis buffer , and the lysates were separated on 12% sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) gels. The separated protein bands were transferred onto nitrocellulose membranes , and the membranes were incubated with anti-cleaved caspase-3 , anti-PARP1/cleaved PARP1 , anti-AIF , anti-Cyto C , and anti-β-actin  antibodies. The membranes were then probed with a secondary horseradish peroxidase (HRP)-conjugated anti-mouse/rabbit IgG  or an anti-goat IgG  secondary antibody overnight. Blots were developed using an enhanced chemiluminescence (ECL) kit  according to the manufacturer’s instructions. The amount of protein was calculated depending on band densities using Fusion Solo software , and the bands were scanned using ImageJ software (NIH).t-test. Histograms for densitometry analysis were obtained using ImageJ (NIH). All data were plotted using GraphPad Prism 5.0 . Differences were considered significant at * p < 0.05, ** p < 0.01, and *** p < 0.001.All percentage data and data sets were subjected to arcsine transformation and expressed as the mean ± standard deviation (SD). All values from western blot and RT-PCR experiments are presented as the mean ± standard error of the mean (SEM). The results were analyzed using one-way analysis of variance (ANOVA) followed by Bonferroni’s and Tukey’s multiple comparison test and In summary, our study provides the first evidence of the toxic effects of TCS on porcine oocyte maturation and cumulus cells in vitro. This report not only reveals the mechanism underlying the toxic effects of TCS on matured porcine COCs after IVM but also highlights the preventive effects of Mito-TEMPO against TCS-induced damage to oocytes.


For the hearing loss group, the hearing threshold was defined as 35 dB nHL or more in the ABR test performed in infants with a ‘refer’ result in the NHS. A four multiple number of infants who had passed the NHS test and matched the age and gender of the hearing loss group were taken as the control group. Various patient factors and treatment factors were taken as hearing loss related variables and were analyzed and compared. From the 2404 infants involved, the prevalence of hearing loss was 1.8% (n = 43). A comparison between the hearing loss group (n = 43) and the control group (n = 172) revealed that history of sepsis, peak total bilirubin, duration of vancomycin use, days of phototherapy, and exposure to loop-inhibiting diuretics were significantly different, and can be verified as significant risk factors for hearing loss in NICU infants.Early detection of hearing loss in neonates is important for normal language development, especially for infants admitted to the neonatal intensive care unit (NICU) because the infants in NICU have a higher incidence of hearing loss than healthy infants. However, the risk factors of hearing loss in infants admitted to the NICU have not been fully acknowledged, especially in Korea, although they may vary according to the circumstances of each country and hospital. In this study, the risk factors of hearing loss in NICU infants were analyzed by using the newborn hearing screening (NHS) and the diagnostic auditory brainstem response (ABR) test results from a 13-year period. A retrospective chart review was performed using a list of NICU infants who had performed NHS from 2004 to 2017 ( Hearing is essential for normal development of the child’s language . HearingHowever, the reported risk factors of hearing loss vary among reports, which may be explained with different conditions such as types of NICU, city- and country-specific circumstances among studies. Although, every country and every hospital should acknowledge their own risk factors for hearing loss, to the best of the author’s knowledge, there are few studies on the risk factors of hearing loss in NICU hospitalized infants in Asia, including Korea. Herein, we evaluated and analyzed the risk factors of hearing loss of NICU infants in Seoul, Korea, over a 13-year period.Long-term retrospective data were collected for 2404 infants who had been hospitalized in NICU longer than 24 h and underwent NHS by means of AABR  or both AABR and OAEs  from July 2004 to November 2017 in Kangnam Sacred Heart Hospital, Seoul, Korea. NHS was performed immediately before discharge when the infant was in good condition. Sound stimulus intensity in AABR was set at 35 dB nHL. In the case of a ‘refer’ result for any ear in AABR, infants were referred for diagnostic ABR test  using an air conduction click stimulus at an otorhinolaryngology outpatient clinic. Hearing loss was defined as an elevated ABR response threshold (≥35 dB nHL) in either ear. All the NICU infants in the study period with the results of NHS were included. Exclusion criteria included those infants without any of NHS results, and those lacking medical information for any patient and treatment factors as described below, such as infants born in other hospitals and admitted to NICU in the study hospital.The hearing loss group included babies whose hearing thresholds were ≥35 dB in ABR, which included unilateral hearing loss. For the control group, to increase statistical power, four times the numbers of infants in the hearing loss group (the first 172 consecutive cases) who had passed in the NHS test were taken , and theFor the patient factors, the following patient and treatment variables were obtained from the medical records of each group: gender, history of germinal matrix hemorrhage, respiratory distress syndrome, cerebral hemorrhage, sepsis, pneumonia, facial anomaly, chromosome anomaly, congenital metabolic disorder, intrauterine infection , Apgar score at 1 min and 5 min, peak total bilirubin, and peak direct bilirubin. For the treatment factors, number of days in NICU, duration of ventilation, days of phototherapy, ototoxic drug usage and duration , and usage of surfactant or blood transfusion were taken.Quantitative variables were described as the number of non-missing values, mean, and standard deviation. Qualitative variables were described as the number and percentage of infants. Missing values were not included in the calculation. For quantitative data where the standard deviation (SD) exceed mean values, we presented median and interquartile range  to avoid bias due to unnormal distribution of data, and in other cases, we expressed the mean and SD.t-test was used for quantitative data. p-values < 0.05 were considered statistically significant.All statistical analyses were performed using SPSS 25 . Initially, all data were analyzed using the Kolmogorov–Smirnov test to assess for normality. Group comparison for qualitative data was performed by the Pearson chi-square test, whereas the Student’s This study was reviewed and approved by the Institutional Review Board (IRB) of the Ethics Committee of Kangnam Sacred Heart Hospital of the Hallym University College of Medicine, Korea . Informed consent was waived by the board due to the retrospective nature of this study. Patients’ confidentiality was protected and their information was anonymized before statistical analysis.From 2004 to 2017, 2404 infants were admitted to the NICU nursery and underwent hearing screening tests. Among them, 2227 infants had ‘pass’ and 177 infants had ‘refer’ in the NHS. The average stay at the NICU was 20.3 ± 31.0 days. The overall referral rate was 7.4% . Of the 177 referred infants, 60 (33.9%) underwent diagnostic ABR at an otorhinolaryngology outpatient clinic. The average age was 17.5 ± 27.9 days at the time of NHS (for the whole 2404 infants), and 193.2 ± 201.3 days (6.4 ± 6.7 months) at the time of diagnostic ABR (for the 60 infants). Among the 60 infants, 43 were finally diagnosed with sensorineural hearing loss . The overall prevalence of hearing loss was 1.8% among all infants. Since not all of the referred infants underwent diagnostic ABR tests, the prevalence of hearing loss was corrected for the ABR rate, resulting in 5.3% . The 43 infants diagnosed with hearing impairment were classified as the hearing loss group, and 172 infants (4 multiples of the hearing loss group) who had passed NHS and matched age and gender to the hearing loss group were selected as the control group. The study process is depicted in The average ages when the NHS was performed were 44.5  days for the control group and 55.0  days for the hearing loss group, with no significant difference between the two groups. The average age when the ABR test was performed for the hearing loss group was 119.0  days .p = 0.003 and p = 0.001, respectively; In the hearing loss group, the following patient risk factors were identified with high incidence: sepsis (62.8%), respiratory distress syndrome (41.9%), congenital metabolic abnormality (25.6%), and pneumonia (16.3%). The order of their prevalence was the same in the control group, but the incidence of the risk factors was lower than that of the hearing loss group. Among these factors, the presence of sepsis and peak total bilirubin was significantly higher for the hearing loss group compared to the control group (p = 0.002), duration of vancomycin use (p = 0.024), and number of infants using loop-inhibiting diuretics (p = 0.003). The cumulative duration of aminoglycoside or ventilation days was longer in the hearing loss group than in the control group, however, there was no significant difference between the two groups. All other factors were not significantly different in the statistical analysis , vancomycin use (44.2%), surfactant use (41.9%), and loop-inhibiting diuretics use (39.5%). However, comparison between hearing loss group and control group showed a statistically significant difference for phototherapy days  days for the control group and 63.0  days for the hearing loss group. The age of the diagnostic ABR of the hearing loss group was 119.0 64.0, 174.0) days. In this study, the follow-up ABR rate of all referred infants was 33.9%, which was lower than that of the Taiwan study (81.4%) [4.0 days..0, 84.8 The auditory system is known to be one of the most susceptible organs to toxic agents. Hyperbilirubinemia is a common cause of hearing impairment in newborns and can also have toxic effects on the central nervous system such as cerebral palsy, epilepsy, or cognitive deficits . The treSeveral studies have demonstrated that exposure to ototoxic medications such as aminoglycoside, vancomycin, and loop-inhibiting diuretics are risk factors of congenital or delayed hearing loss ,13,23,24Several publications have evaluated the risk factors of hearing loss in NICU; a Dutch study found that dysmorphic features, low 1-min Apgar scores, sepsis, meningitis, cerebral bleeding, and cerebral infarction were associated with hearing loss , and a Mn = 43). Although, the statistical power of the study was increased by selecting four controls per case  [The limitations of this study for the analysis of the status of NHS were that it investigated only up to until the final diagnosis of hearing loss, and no follow-up was conducted after the intervention for hearing loss such as hearing aids or cochlear implantation because most rehabilitation treatments were performed at other children’s hospitals and no medical records were available to us. Another limitation was the small size of the hearing loss group (eds 1:4) , segmentIn summary, history of sepsis, peak total bilirubin, duration of vancomycin use, the number of days of phototherapy, and the use of LIDs were significant risk factors for hearing loss in NICU infants in Korea. These factors should be considered in NICU infant care and also in counseling parents of the NICU graduates.


Dementia is affecting both the person with the disease and the family members. It is associated with nursing home admission, and a reduced ability to perform personal activities of daily living (P-ADL). The aim of this study was to examine the association between the severity of dementia and P-ADL function, and to study if additional factors such as neuropsychiatric symptoms, type of nursing home unit, and use of medication were associated with P-ADL function.A total of 582 nursing home residents with dementia, included at admission to the nursing home, were followed with biannual assessments for 36 months. P-ADL was assessed using the Physical Self-Maintenance scale, and severity of dementia was measured with the Clinical Dementia Rating scale. In addition, neuropsychiatric symptoms, general physical health, and use of medications were assessed at the same time points. Demographic information was collected at baseline. Linear mixed models were estimated.p < 0.05) non-linear decline in P-ADL function over time in analysis not adjusting for any characteristics. More severe dementia at baseline and at the follow-up assessments was associated with lower P-ADL function (p < 0.001), with the association being stable over time. A higher level of neuropsychiatric symptoms, not using anti-dementia medication, being in a regular care unit as compared to a special care unit and having poor/fair general physical health as compared to good/excellent, were associated with a lower P-ADL function.There was a significant (The association between more severe dementia and lower P-ADL function was stable over a 36-month follow-up period of nursing home residents with dementia. Health care planners and clinicians should be aware of this when planning for and treating nursing home residents. Newly published data from the United Nations (UN), state that the number of people aged 65 years or older in Europe, has increased from 8% in 1950 to 19% in 2019, and it is expected that the proportion of the elderly in the society will continue to increase , leadingIn Norway, unlike many other countries, the health care services are public , 5. The Dementia is a syndrome caused by a variety of brain disorders, usually of a chronic progressive nature. A progressive decline in cognitive function is one of the main characteristics of dementia. The primary risk factor for developing dementia is age, and therefore, the rising life expectancies in the society will increase the number of people who develop dementia . The leaActivities of daily living (ADL) describes the ability to perform practical everyday tasks necessary for basic, and more complex self-care. It consists of instrumental ADL (I-ADL), with complex, higher order skills, and personal ADL (P-ADL), with self-maintenance skills, such as dressing, eating, bathing and toileting. A decline in P-ADL causes individuals to become more dependent of the caregivers and professional support , 34, 35.The association between dementia and declined P-ADL function has been assessed in several studies and settings , 36–39, To our knowledge, there are only two studies that have described the course of P-ADL, adjusted for variables known to have an influence on P-ADL function , 31. OneThe aim of this study was to examine if and how P-ADL assessed biannually over 36 months changed over time in NH residents. The primary aim was to explore the association between the severity of dementia and P-ADL function over time in NH residents. The secondary aim was to assess if and how additional factors such as neuropsychiatric symptoms, type of NH unit and use of medication were associated with the outcome.1) until the 36-month follow-up (T7).The data was collected from the REDIC-NH study, an observational longitudinal study including participants from a convenience sample of 47 NHs in four Norwegian counties, from both small and large NHs, located in urban and rural areas . The basIn total, 696 residents with an expected stay longer than four weeks were recruited at admission to the NH. Out of these, 583 had dementia . All resThe outcome variable, personal activities of daily living (P-ADL), was assessed with the Physical Self-Maintenance Scale (PSMS)  in a traSeverity of dementia was measured with the Clinical Dementia Rating (CDR) scale. The scale covers six domains , each with five response alternatives  , 46. TheNeuropsychiatric symptoms (NPS) were measured using a translated and validated Norwegian version of the Neuropsychiatric Inventory 12-item Nursing Home version (NPI-NH), including the following symptoms: delusion, hallucination, agitation/aggression, depression/dysphoria, anxiety, euphoria, apathy/indifference, disinhibition, irritability/lability, aberrant motor behavior, night-time behavior disturbances, and appetite and eating disorders , 50. To General physical health was assessed using the General Medical Health Rating (GMHR) scale, a one-item global rating scale with four response categories: poor, fair, good and excellent . The scaUse of psychotropic medications was collected from the medical record of each resident, using the Anatomic Therapeutic Chemical (ACT) Classification System. The medications were grouped into the following categories: antipsychotics (N05A except lithium), antidepressants (N06A), anxiolytics (N05B), hypnotics/sedatives (N05C), and anti-dementia medication (N06D) .Demographic information such as gender, age and marital status was collected from the medical records.The data collection was performed by healthcare workers in the NHs, mainly registered nurses (74%), under the supervision of 10 research nurses who had completed a five-day training program. The data collectors went through a two-day training program prior to the data collection. The training program included lessons on dementia, old-age psychiatry, geriatric assessment, and routines for data-collection, ethics, and research principles, in addition to practical training in assessment of participants. The data was collected from the medical records of each resident, and from a standardized interview with the residents, the next of kin and the residents’ caregivers in the NH.Norwegian Act on medical and health research [The residents’ capacity to consent to participate in the study was considered by the NH staff, including the NH physician. A written consent for the participation was obtained from all residents who had the capacity to give consent. If a resident was lacking the capacity to give consent, their next of kin gave written consent on behalf of the resident, in line with the research . The Regresearch .Sample characteristics at baseline were presented as means and standard deviations (SD) or frequencies and percentages.A linear mixed model with fixed effects for nonlinear (third order) time component was estimated first to assess time trend in P-ADL-scores. Next, two models were estimated with CDR-SoB as additional fixed effect along with interaction terms between CDR-SoB and time. Model 1 included CDR-SoB assessed at baseline, while CDR-SoB measured simultaneously with P-ADL was included into Model 2. A significant interaction between CDR-SoB and time would imply a varying association between CDR-SoB and P-ADL throughout the follow-up period. Finally, Model 1 was adjusted for predefined clinical and demographic characteristics all measured at baseline, while Model 2 was adjusted for characteristics measured longitudinally whenever possible. All models included random effects for residents nested within NHs. Even though the linear mixed model allows inclusion of all available observations, also from dropouts, the dropouts may introduce bias. Therefore, baseline characteristics of dropouts and those staying in the study were compared.P-values below 0.05 were considered statistically significant. All tests were two-sided.All analyses were performed in SPSS version 25 and SAS version 9.4. Results with N = 354). Those leaving the study were older (p = 0.001), had higher PSMS score (p < 0.001), higher NPI- affective sub-syndrome score (p = 0.017), were more often males (p = 0.026), and hade more often poor/fair GMHR (p < 0.001).The total number of participants assessed at baseline for P-ADL was 582. The mean (SD) age of these participants was 84.1 (7.5) years, ranging from 49 to 105 years. In total, 374 (64.3%) of the participants were women , having poor/fair as compared to good/excellent GMHR (p < 0.001) and more apathy (p = 0.029) at baseline were associated with lower P-ADL function at each assessment.In both unadjusted and adjusted Model 1 Table , higher p < 0.001), more apathy (p < 0.001), agitation sub-syndrome (p = 0.002), affective sub-syndrome (p = 0.001), not using anti-dementia medication (p < 0.001), and being a Regular unit (RU) resident compared to a Special care unit (SCU) resident (p = 0.009), all assessed simultaneously with P-ADL, were significantly associated with a lower P-ADL function.In unadjusted and adjusted Model 2 Table , higher This study of 582 NH residents with established dementia, followed with biannual assessments from admission to 36 months, showed that the degree of dementia (assessed with the CDR-SoB) at baseline, and the course of dementia at the follow-up assessments, were associated with the degree of P-ADL function. More severe dementia both at baseline and at the follow-up assessments was associated with lower P-ADL function, with the association being stable over time.When looking at the P-ADL function adjusted for dementia assessed simultaneously with P-ADL, there was a decline in P-ADL function over time, both in unadjusted and adjusted models. This is in line with previous studies, both among NH residents and community dwelling elderly with dementia , 36–39. Many studies have shown that more severe dementia is associated with lower P-ADL function in NH residents , 36–38. It could be questioned whether the P-ADL of an individual with dementia under 65 years could be compared to the P-ADL of an older person with dementia. Our clinical experience is that those being admitted to a Norwegian nursing home with dementia are in a state that makes municipal domiciliary care insufficient, due to dementia, P-ADL function and/or NPS, independent of age. With the PSMS scale assessing very basic activities of daily living, the measured P-ADL are comparable even if the age range of those admitted to the nursing home are broad. Nevertheless, age adjustments in the analysis should be performed, as was done in this study. However, in the present nursing home study where all participants were included at admission to the nursing home, we did not find an association between age and P-ADL or decline in P-ADL. In line with this finding, a Japanese study of persons with dementia living at home found no difference in P-ADL decline in those of 75 years or older compared to younger people . HoweverIn several previous studies, both among participants with and without dementia, NPS have been found to be associated with P-ADL function , 60–62. In the present study, the use of anti-dementia medication was associated with a better P-ADL function, which is in line with previous studies , 34, 65.As expected, there was an association between P-ADL function and GMHR. In addition, it was found that belonging to a SCU at a NH was associated with better P-ADL function, compared to those who belonged to a RU. We do not know if the reasons for getting these results are due to differences in the structure and staffing between RU and SCU, or other factors, such as rest confounding.One of the main strengths of the present study, is that all the participants were included at the time they were admitted to the NH, and they were followed with biannual assessments for a long follow-up time 36 months). Furthermore, the study used several validated measuring tools, such as PSMS for P-ADL and NPI-NH for NPS. In addition, the results in the present study were adjusted for variables known to have an influence on P-ADL function, in contrast to many previous similar studies , 36, 37. months. Despite the strengths of the study, there are also limitations. The main weakness in this study is many dropouts, mostly due to death, leading to fewer participants and less data collected. To accommodate any degree of imbalance in the data, a linear mixed model was used. This model is well-suited for analysing data with missing values and dropouts, by including all available data. However, those leaving the study were older and had poorer functioning and physical health than those participating. These findings may imply some degree of bias, but they also indicate that the decline in P-ADL might be underestimated rather than overestimated.Due to the prospective design of the study, it was necessary to include all NH residents when they were admitted to a NH. In order to restrict time of inclusion, the study included new residents at several NHs over a large geographical area. We consider this as a strength, because it gives a better representativity than including only a few NHs over a smaller geographical area. On the other hand, it also led to many research coordinators and data collectors involved in the study. This may have caused some differences in interpreting the assessment protocol and tools, which might have reduced the data validity. To secure as high validity of the data as possible, the research coordinators completed a five-day training program, and the data collectors completed a two-day training program, prior to the data collection. Despite this, we cannot rule out the possibility of differences in the data collection.It is also worth mentioning the proxy reporting of P-ADL and symptoms as a potential source for bias, however, it is recommended that P-ADL functioning is based in observation by care-taker in individuals with more severe cognitive impairment , 67.Even though the study adjusted for many variables relevant for P-ADL function, the analysis did not include information about education. Some previous studies have shown that educational background has an impact on P-ADL function –70. HoweN = 582 at baseline, and N = 166 at 36-months), found that more severe dementia at baseline and at the follow-up assessments was associated with lower P-ADL function. This association was stable over time. The health care planners and clinicians should therefore pay attention to degree of dementia, and other factors associated with P-ADL function in NH residents, in order to improve the quality of care for the residents with dementia, and to help maintain their level of function as long as possible.This 36-months longitudinally study of NH residents with dementia, followed with biannual assessments (


To identify the presence of any correlative factors between presenting symptoms and characteristics of asymmetrical sensorineural hearing loss on audiogram, and if retrocochlear pathology was identified on MRI in patients presenting in a private practice setting.A retrospective study of patients meeting inclusion criteria who underwent MRI for asymmetric hearing loss between March 2014 to March 2017 was reviewed using Allscripts electronic health records. This data was then compiled in an excel spreadsheet and submitted for statistical analysis.Of the initial 687 study patients, N = 303 patients met the inclusion criteria for review. Of these 303, 48 patients (15.8%) had abnormal MRI findings. Chi-square analysis performed showed no significant association of varied clinical variables  with abnormal MRI. Point Biserial Correlation analysis revealed no statistically significant correlations, with the exception of that between AS (Left Ear) 6 kHz and MRI lesions . Logistic and multinomial logistic regression analysis used to calculate odds ratios showed that for patients with hearing loss at the 6 kHz (dB) level, there is a very slightly lower, statistically significant likelihood of lesions showing up on MRI , p = 0.0251).The results lead to the conclusion that there may be an association between experiencing hearing loss at the level of 6 kHz and a slightly lower chance of the presence of retrocochlear lesion noted on MRI. When a patient presents with asymmetrical sensorineural hearing loss, a variety of etiologies must be considered. These causes may arise from a number of categories including: infectious, pharmacologic ototoxicity, acoustic trauma, metabolic or autoimmune disorders, and neoplasms.Vestibular schwannoma, also called acoustic neuroma, is the most common tumor of the cerebellopontine angle (located between the cerebellum and pons) and often presents with unilateral or asymmetric sensorineural hearing loss .The goal of this study was to retrospectively identify the presence of any correlative factors between presenting symptoms and characteristics of asymmetrical sensorineural hearing loss on audiogram, and whether or not retrocochlear pathology was identified on MRI in patients presenting in a private practice setting. Findings from this research may help guide further evaluation of asymmetrical sensorineural hearing loss in the private practice setting and possibly avoid low-yield MRI testing by identifying characteristic criteria. This would, in turn, aim to decrease unnecessary health care costs.After McLaren Oakland institutional review board approval was obtained, the authors  completed a query of Allscripts electronic health records from North Oakland Ear, Nose & Throat Centers. They initially identified a total of 687 patients who underwent MRI for asymmetric hearing loss between March 2014 and March 2017. A retrospective review of these patient charts was performed. Investigators were supplied with a user-specific login to access the patient charts, and data from each chart was recorded in an excel spreadsheet. Patients were assigned a unique numerical identifier on the spreadsheet to protect their identities. The specific data elements recorded from the history and physical of each chart included:AgeSexOnset of hearing loss Presence or absence of tinnitus Presence or absence of vertigoPresence or absence of disequilibrium or imbalancePresence or absence of aural fullness or otalgiaPresence or absence of subjective hearing loss Audiogram findings Hearing threshold levels = octave frequencies 250-8000 Hz were usedHz = hertz, unit of frequencySpeech discrimination score = reflects percentage of phonetically balanced words that a patient repeats correctlyMRI results , or presence of vestibular schwannoma and size of lesion)Patients with asymmetrical sensorineural hearing loss  underwent MRI to evaluate for retrocochlear causes of asymmetrical sensorineural hearing loss.Patients with recent head trauma or use of chemotherapeutic or ototoxic medications.Remaining patients who did not meet the inclusion criteria.Data from these patient charts were compiled in a spreadsheet and submitted for statistical analysis to the third author (SJW) at the Michigan State University College of Osteopathic Medicine Statewide Campus System.Initial analyses assessed whether there were any correlations between the exposure  and the outcome (retrocochlear lesion noted on MRI). Also taken into account were factors that could play a part in the relationship between the exposure and outcome. These potential confounding factors included imbalance, vertigo, tinnitus , the degree of hearing loss, and otalgia. As such, bivariate correlations were examined,  along with whether a normal or abnormal MRI result was observed. Logistic regression modeling was then performed using the proc logistic function, examining those correlations observed to be significant in the bivariate correlations analyses, in combination with the potential confounding variables . All analyses were performed by the third author (SJW) using SPSS Version 24. An alpha cut-off of < 0.05 was considered statistically significant for all analyses.very slightly lower, statistically significant likelihood of lesions showing up on MRI, OR, 0.984 , p value = 0.0251.Of the initial 687 study patients, N = 303 (44%) patients met the inclusion criteria for review. Of these 303, 48 patients (15.8%) had abnormal MRI findings (Table 1). Chi-square analysis performed showed no significant association of clinical variables with abnormal MRI (Table 2). Point Biserial Correlation analysis revealed no statistically significant correlations, with the exception of that between AS (Left Ear) 6 kHz and MRI lesions  (Table 3). This suggests that there may be an association between experiencing hearing loss at the level of 6 kHz and the presence of retrocochlear lesion noted on MRI. Further analyses utilizing logistic and multinomial logistic regression to calculate the odds ratio (OR) showed that for patients with hearing loss at the 6 kHz level, there was a et al., all patients that present with asymmetrical hearing loss or unilateral audiovestibular dysfunction will obtain an MRI, leading to a considerable amount of MRIs with negative findings as the incidence of acoustic neuroma in their screening population varies from 1% to 4.7%. This equates to more than 95% of MRIs resulting negative for acoustic neuroma.One of the cardinal features of acoustic neuroma is the presence of an asymmetric sensorineural hearing loss, and the most frequent presenting symptoms of acoustic neuroma occurring in greater than 95% of patients is hearing loss.The goal of our retrospective study was to identify the presence of any correlative factors between presenting symptoms and characteristics of asymmetrical sensorineural hearing loss on audiogram, and whether or not retrocochlear pathology was identified on MRI in patients presenting in a private practice setting. Overall, results showed that there appears to be very little difference, if any, in the clinical and/or audiometric findings of those with or without retrocochlear lesions assessed via MRI in private practice setting. One correlation noted in our study was that those with hearing loss at the 6 kHz level showed a slightly lower likelihood of lesions observed on MRI. Further analysis (logistic regression) used to calculate odds ratios demonstrated a slightly lower odds that those with hearing loss at the 6 kHz level were likely to have lesions show up on MRI . However, this OR approaches very closely to 1, so much so that rounding the higher end of the confidence interval (CI) would actually be 1. This is within a margin of error and suggests that any significance observed is likely the result of statistical noise (i.e. unmeasured confounding factors).The discussion is then what other data in the literature can help further guide evaluation of asymmetrical sensorineural hearing loss and potentially avoid uneccesary low-yield MRI testing by identifying other characteristic criteria, and thus decreasing health care costs. In reviewing the literature, Saliba et al., proposed the rule of 3,000. They state patients with asymmetrical sensorineural hearing loss of 15 dB or more at the 3 kHz warrant an investigation with MRI and that if the asymmetrical sensorineural hearing loss is less than 15 dB, a biannual audiometric follow-up is recommended.A limitation to this study is the limited number of our population in a private setting, as we only reviewed N = 303 patients that met our inclusion criteria. A future study with a more generalizable sample (i.e. not limited to the private setting population) could provide improved external validity.The purpose of this study was to identify possible correlations between presenting symptoms and characteristics of asymmetrical sensorineural hearing loss on audiogram, and if retrocochlear pathology was observed on MRI in patients within the setting of private practice. A retrospective chart review was conducted; following the statistical analysis of N = 303 patient charts, there was very little difference found between the clinical and/or audiometric findings in patients with or without retrocochlear lesions on MRI. This is with the exception found between those with hearing loss at the 6 kHz level and having a slightly lower likelihood of retrocochlear lesion on MRI findings. Further investigation into potential correlations between findings on clinical exam, audiogram, and MRI will be necessary. These future studies should be conducted on larger sample sizes in both private practice and non-private practice settings in hopes of creating a more concise medical decision-making process for ordering MRI to rule out retrocochlear lesion.The authors declare no conflict of interest.


To determine whether the use of a magnetic tracking and electrocardiography-guided catheter tip confirmation system (TCS) is safe and noninferior to fluoroscopy concerning positioning accuracy of a peripheral inserted central catheter (PICC).In this prospective, randomized, single-center study, adult patients scheduled for PICC insertion were assigned 1:1 either to TCS or fluoroscopy. The primary objective was a noninferiority comparison of correct PICC tip position confirmed by X-ray obtained immediately after catheter insertion. Time needed for PICC insertion and insertion-related complications up to 14 days after the procedure were secondary outcomes to be assessed for superiority.p > 0.99). Insertion of PICC took longer with TCS compared to fluoroscopy . Incidence of complications within a mean follow-up of 5.0 ± 2.3 days did not differ significantly between groups.A total of 210 patients  were included at a single German center between June 2016 and October 2017. Correct PICC tip position was achieved in 84 of 103 TCS (82.4%) and 103 of 104 fluoroscopy patients (99.0%). One-sided 95% lower confidence limit on the difference between proportions was −23.1%. Thus, noninferiority of TCS was not established . Peripherally inserted central catheters (PICC) are widely used to provide central venous access for infusion of irritant drugs, parenteral nutrition, long-term drug administration, repeat blood sampling, monitoring of circulatory functions, or as alternative for patients with poor peripheral access.PICC insertion, particularly in the case of malposition, however, may cause complications including malfunction, cardiac arrhythmia, or tamponade . In addiCurrently, there are several approaches of PICC insertion. The classic technique of blind PICC insertion toward a target tip position according to an earlier determined distance between puncture site and an anatomical landmark can be conducted at bedside. However, malposition of PICC is given as 20–76% , 4 and XOur study aimed to compare incidences of accurate PICC tip position between TCS and fluoroscopy and to examine whether TCS is noninferior to fluoroscopy. In addition, we sought to investigate early PICC insertion-related complications within 14 days after PICC implantation.The study was a prospective, randomized, open-label, single-center, investigator initiated, noninferiority trial that sought to determine whether PICC insertion using TCS is noninferior to fluoroscopy regarding the incidence of correct PICC tip position confirmed by chest X-ray. Eligible patients were allocated 1:1 to either TCS or fluoroscopy by means of computer-generated randomization. The study is registered with Clinical.Trials.gov (Identifier: NCT02929368).P-wave morphology when using the TCS system. Patients were recruited from different medical departments of the center.Patients were eligible for inclusion if they were at least 18 years of age and had a medical indication for PICC insertion. Exclusion criteria were systemic infection, infection including puncture site, and known allergy to materials used. Additionally, cardiac arrhythmia including atrial fibrillation, severe tachycardia, or paced rhythm was exclusion criterion because it could interfere with interpretation of the PICC insertion was conducted either in the radiology department (fluoroscopy group) or at bedside (TCS group). However, both approaches were carried out by experienced interventional radiologists. Initially, ultrasound was used to identify a suitable vein in the upper arm, preferably the right basilic vein. The vein was punctured, and a guidewire inserted. In the control group, the guidewire was advanced under fluoroscopic control through the axillary and subclavian vein toward the target position near the cavoatrial junction. Length of the guidewire was measured to determine the required PICC length. Subsequently, an introducer sheath was inserted over the wire, the guidewire was removed, and the PICC catheter inserted through the introducer sheath and then advanced under fluoroscopic control to the predetermined length. The same PICC kit type in different sizes was used in all patients.® TCS  was used for magnetic tracking of the PICC tip and real-time ECG confirmation of the tip position during insertion . Placement of the catheter was confirmed by obtaining chest X-ray.Correct PICC tip position was defined as within the mid to lower superior vena cava, at the level of the cavoatrial junction, or within the upper portion of the right atrium, corresponding to 1.5 vertebral body units  from the tracheal carina on chest X-ray obtained immediately after insertion. Time for PICC insertion started from introduction of the guidewire into the vein and ended with stabilization of the catheter on the arm. In order to assess catheter-related complications, patients were followed up within 2 weeks after PICC insertion. Patients were considered lost to follow up at withdrawal of the catheter.U test or Fisher’s exact test. A two-sided value of p < 0.05 was considered to indicate statistical significance. Analysis was performed using XLSTAT .Sample size was calculated based on results from a post-market clinical trial on Sherlock 3CG TCS initiated by the manufacturer and described in manufacturers instruction for use that reported acceptable PICC placement in 99.1% of patients. We assumed an incidence of 98.0% success using fluoroscopy. Given a noninferiority margin of 5% and a one-sided 5% level of significance, a sample size of 210 patients was sufficient to establish noninferiority with 98% power. At a significance level of 0.05, noninferiority of TCS compared to fluoroscopy could be claimed if the lower bound of the one-sided 95% CI for the difference in proportions of proper tip position was greater than −5%. The calculation allowed for 10% dropout. Analysis was performed based on intention to treat. The test for noninferiority was only applied for the primary endpoint. All other analyses were tests of superiority. Logistic regression was applied to determine odds of malposition in obese patients. To assess consistency in the effect of TCS across selected patient characteristics, a post hoc subgroup analysis was performed. Continuous variables are reported as means and standard deviations, and categorical variables are presented as counts and percentages. Variables were compared by means of Mann–Whitney 2). Insertion of PICC using TCS took significantly longer compared to fluoroscopy  . The two-sided 95% CI was entirely below the noninferior margin, and therefore demonstrated inferiority of TCS over fluoroscopy  . However, age, sex, and BMI did not interact with the effect of TCS .Incidence of correct PICC tip position was 82.4% (84 of 102) in the TCS group and 99.0% 103 of 104) in the fluoroscopy group. The lower bound of a one-sided 95% confidence interval (CI) of −23.1% difference in proportions of proper tip position was below the prespecified boundary of −5%. Thus, noninferiority of TCS compared to fluoroscopy was not established   and Yama.5%  and P-wave could not be used as reliable parameter for ECG guidance. However, according to manufacturer, an altered or pacemaker-driven cardiac rhythm is considered limiting but not contraindicated. Proper PICC tip location should, however, be confirmed with chest X-ray. Regarding a 10% prevalence of atrial fibrillation in patients from 65 years of age [f-waves in successive TQ-segments for catheter tip location in atrial fibrillation patients [Cardiac arrhythmia including atrial fibrillation, severe tachycardia, or paced rhythm was exclusion criterion in our study because s of age , we conss of age . Moreovepatients .2 [P-wave, in particular in the case of weak TCS signal.In our study, a weak signal from the magnetic stylet of the PICC tip to the display monitor impeded tip localization and navigation in about 16% of TCS patients resulting in final malposition in one-third of them. Although obesity increased the odds of malposition with both TCS and fluoroscopy, it did not interact with the effect of TCS nor was it associated with a weak signal. In order not to lose the signal, PICC had to be advanced slowly and carefully, resulting in prolonged insertion time compared to fluoroscopy. However, latter entails a radiation exposure of about 60 µGym2 . FinallyAlthough, our study did not prove any interaction of sex and age with the effect of TCS, female and elderly patients tended to benefit more from fluoroscopy. Whether osteoporosis-related reduction in the vertebral body height might affect radiographic assessment  remains Malposition may increase the risk of catheter tip migration and thus promote thrombosis and infection , 6, 15 pThe short follow-up period of 14 days does not permit final conclusions on safety. However, we focused on insertion-related complications, not on safety of PICC in general. Thus, a relatively short follow-up period might be considered appropriate. In addition, we did not consider morbidity of patients. There might have been different results in critical ill compared to normally hospitalized patients. Requirement for confirmatory chest X-ray in the TCS group was not determined because in our study, chest X-ray was mandatory to evaluate tip position accuracy. No data were available whether PICC had to be adjusted or reinserted in the case of initial malposition. Finally, to date, there is no consistent definition of an optimal catheter tip position. Therefore, malposition rates could have differed if only the lower vena cava and the cavoatrial junction were considered correct. Finally, we did not consider costs.TCS for PICC insertion was associated with less tip position accuracy than fluoroscopy. However, it was associated with reasonable success and a similar complication rate. For this reason, we conclude that TCS would be most useful in patients where fluoroscopy cannot be used, bedside placement is necessary, or resources are limited.


Cerebellar lesions could be a cause of fluctuating hearing loss, due to the increase of intracranial pressure by partially or complete blocking of the Foramen of Luschka. Patients with intracranial hypertension may present audio‐vestibular symptoms. Fluctuating sensorineural hearing loss may be the manifestation of different inner ear disorders such as Meniere's disease (MD), immune‐mediated inner ear disease (IMIED), otosyphilis, and labyrinthine fistula including semicircular canal dehiscence. A rare mechanism involved in the fluctuating hearing loss is the increase in cerebrospinal fluid (CSF) pressure, that may be caused by a cerebellar tumor. A 51‐year‐old female presented a 2‐year history of left ear fluctuating hearing loss and tinnitus, with fluctuations among the day, and normal otoscopy. Several audiometries showed a left ear moderate sensorineural hearing loss in low frequencies . The patient underwent a cerebral magnetic resonance imaging (MRI) . She was treated with three courses of systemic steroids showing improvement of symptoms during the treatment. However, the symptoms always returned when corticotherapy was interrupted. The patient was given two intratympanic steroids cycles combined with hydrochlorothiazide/ amiloride hydrochloride. The cerebral MRI described a left cerebellar focal lesion diagnosed as a cerebellar gangliocytoma. After receiving the second intratympanic steroids, cycle combined with systemic ameride showed a significant improvement of audition. Between the several causes of fluctuating hearing loss, a cerebellar gangliocytoma is a very rare disease, which needs a high degree of suspicion and otorhinolaryngologists should be familiar with this entity since patients may present with audiological and vestibular symptoms. Cerebellar lesions could be a cause of fluctuating hearing loss, due to the increase of intracranial pressure by partially or complete blocking of the Foramen of Luschka. Patients with intracranial hypertension may present audio‐vestibular symptoms. Fluctuating sensorineural hearing loss may be the manifestation of different inner ear disorders such as Meniere's disease (MD), immune‐mediated inner ear disease (IMIED), otosyphilis, and labyrinthine fistula including semicircular canal dehiscence. A rare mechanism involved in the fluctuating hearing loss is the increase in cerebrospinal fluid (CSF) pressure, that may be caused by a cerebellar tumor. A 51‐year‐old female presented a 2‐year history of left ear fluctuating hearing loss and tinnitus, with fluctuations among the day, and normal otoscopy. Several audiometries showed a left ear moderate sensorineural hearing loss in low frequencies . The patient underwent a cerebral magnetic resonance imaging (MRI) . She was treated with three courses of systemic steroids showing improvement of symptoms during the treatment. However, the symptoms always returned when corticotherapy was interrupted. The patient was given two intratympanic steroids cycles combined with hydrochlorothiazide/ amiloride hydrochloride. The cerebral MRI described a left cerebellar focal lesion diagnosed as a cerebellar gangliocytoma. After receiving the second intratympanic steroids, cycle combined with systemic ameride showed a significant improvement of audition. Between the several causes of fluctuating hearing loss, a cerebellar gangliocytoma is a very rare disease, which needs a high degree of suspicion and otorhinolaryngologists should be familiar with this entity since patients may present with audiological and vestibular symptoms. Some possible causes of fluctuating hearing loss are Meniere's disease, immune‐mediated inner ear disease (IMIED), otosyphilis, and labyrinthine fistula including semicircular canal dehiscence.2A 51‐year‐old female presented a 2‐year history of left ear fluctuating hearing loss and tinnitus, with fluctuations among the day, without a clear relation to posture, not associated to dizziness or vertigo. Also presents morning headaches that disappeared 2 hours after she wakes up. Physical examination revealed a normal otoscopy. She was treated with three courses of systemic steroids (methylprednisolone: descending dosis starting with 1mg/kilogram/day) showing improvement of symptoms during the treatment. However, the symptoms always returned when corticotherapy was interrupted. The patient was given three intratympanic steroids cycles (0.7 mL methylprednisolone), symptoms improved in the second cycle coinciding with the start of treatment with hydrochlorothiazide/ amiloride hydrochloride. Several audiometries showed a left ear moderate sensorineural hearing loss in low frequencies .MRI images show tumors hyperintense on T2, with variable contrast enhancement: none, ring/solid enhancement. These lesions may have cysts (50% of cases) or calcifications (30%) inside.It is a rare disease with a low incidence, and it is more common in children and young adults. If the tumor required intervention, the main treatment is surgery.Cerebellar gangliocytoma is part of a group of uncommon tumors constituted by neuronal‐glial tumors, with variable degree of neuronal and glial differentiation. Other tumors classified in this category are as follows: dysembryoplastic neuroepithelial tumor, dysplastic gangliocytoma of the cerebellum (Lhermitte‐Duclos disease), papillary glioneuronal tumor, paragangliomas, among others.Dysplastic cerebellar gangliocytoma, Lhermitte‐Duclos disease, is an extremely rare tumor that affects cerebellar architecture, with abnormally hypertrophic ganglion cells and hypoplasia of cerebellar white matter. Arises from hemispheres but may extend to vermis. Clinical presentation is characterized by cerebellar dysfunction symptoms and obstructive hydrocephalus. Its typical MRI image is nonenhancing, well‐delimited lesion, T1 hypotense, and laminar pattern in T2 images with alternating high and low signal.The radiological pattern of this case does not suggest a Lhermitte‐Duclos disease.A rare mechanism involved in the fluctuating hearing loss is the increase of cerebrospinal fluid (CSF) pressure. It may be transmitted to the subarachnoid space surrounding the acoustic nerve and to the perilymphatic space resulting in arrest of the blood supply to the acoustic nerve and impaired movement of the footplate of the stapes.Patients affected by idiopathic intracranial hypertension and patients suffering from tumors blocking the CSF flow may present audio‐vestibular symptoms.In the present report, MRI imaging revealed a tumor (cerebellar gangliocytoma) in close proximity to the left wall of the fourth ventricle, partially blocking the Foramen of Luschka.Fluctuating hearing loss in the left ear was confirmed in our patient, and a transient intracranial pressure modification was hypothesized as the probable cause.‐The acoustic nerve may suffer functional disturbances or anoxia due to transmission of intracranial pressure through the sheet from the subarachnoid space‐Direct pressure transmission via the perilymphatic space or the cochlear aqueduct resulting in reduced cochlear blood flow, venous congestion, stretching of the basilar membrane, inducing perilymphatic and endolymphatic pressure alterations, and thereby hindering mobility of the footplate.Several mechanisms have been postulated:Our patient showed lower frequency hearing loss suggesting a similar mechanism as in the endolymphatic hydrops observed in MD and IMIED Hearing loss improved with the administration of systemic and intratympanic corticosteroids since these drugs may induce expression of aquaporin‐1 and increase transcellular water transport in the inner ear, mainly in the stria vascularis and the endolymphatic sac.The symptoms also improved with diuretics, which decreased CSF production and intracranial pressure. This fact also supports the hypothesis of hearing loss induced by transient intracranial pressure modification due to a cerebellar tumor.In conclusion, cerebellar gangliocytoma is a very rare disease, which needs a high degree of suspicion in patients with a cerebellar mass, and otorhinolaryngologists should be familiar with this entity since patients may present audiological and vestibular symptoms, occasionally fluctuating hearing loss.None declared.Ana Julia Rocha and Reyes Marquez Altemir: have been involved in drafting the manuscript and revising it critically for important intellectual content. Jose Ramón Garcia Berrocal: has given final approval of the version to be published.The patient gave verbal consent for including data and radiological images in this publication.


The increase in the proportion of elderly people in most industrialized countries triggers higher demand for long-term care (LTC) associated with limitations in activities of daily living (ADL). The aim of this research is to derive the drivers affecting the probability of reporting limitations in ADL and the probability of demanding formal LTC, e.g., personal care and services in domestic tasks. By using the most recent wave of a cross-national European survey on individuals aged over 50 years , we develop econometric models for identifying the effect of demographic, social and medical factors on ADL limitations and formal LTC along five conjectures. On the one hand, we analyze functional limitations and we find that characteristics such as the age, the gender, the wealth status and the education level influence the probability to report limitations. Further, while we find that pathologies significantly increase the probability to become dependent in general, the effect of cancer is lower. On the other hand, we find again an influence of the demographic and social factors on the probability to use formal LTC. We emphasize on the decrease in the probability due to the presence of the partner in the household, in particular for housekeeping tasks. This is less the case for help related with personal care. In addition, we note that pathologies such as cancer have no influence on the probability to report formal LTC while others like mental and Parkinson diseases highly increase it. We find that elderly living in countries with LTC family care schemes report less formal care than in others. This indicates the importance of LTC policies. Finally, we validate the robustness of our results by applying the models to data from earlier waves of the survey. Our findings give insights for the underwriting standards to be used in future LTC insurance products and for the design of LTC policy environments across Europe. Handling the forthcoming high number of elderly and in particular the financing threat and infrastructure needs due to the demand for long-term care (LTC) is at the foreground of many policy debates in Europe . In thisIn this paper, we first study the reporting of limitations in ADL among elderly in Europe for understanding how demographic, social and medical factors affect them. Limitations in ADL are essential in measuring LTC needs and many factors can affect them. Usually, at high ages, women have more chances than men to present functional limitations . The socOur main results quantify the relevance of demographic, social and medical factors on both the probability to report limitations in ADL and formal LTC usage in Europe. From the cross-national study, we find that demographic factors such as the age and the gender have a strong influence on ADL limitations. For ages above 80 years, women are more likely to present limitations than men are. Further, poorer health conditions such as presenting a body mass index away from normal weight as well as being diagnosed with mental, Parkinson, cancer, musculoskeletal system and other physical diseases increase the probability to be dependent. We observe that mental and Parkinson diseases come along with more limitations when compared to other pathologies. Our study also highlights the role of wealth and education in defining elderly health. With higher education, higher wealth and living together with their partner, elderly tend to report fewer ADL limitations. When detailing our results by type of ADL, we observe that the presence of the partner in the household mostly reduces the claiming of difficulties with bathing. Moreover, when considering the probability to report formal LTC, we find that elderly living with their partner require significantly fewer professional services highlighting the importance of informal care. This effect is particularly affecting domestic tasks while for personal care the presence of the partner does not reduce the claiming behavior. Another interesting outcome is related to the country’s specific LTC policy. Countries with family care schemes, like Italy or Spain, rely more extensively on family members for delivering LTC and appear in our study to strongly decrease the probability for requesting formal LTC. Finally, by considering pathologies, we note that formal LTC is also more often required in cases where mental and Parkinson diseases are diagnosed. We observe that, while some diseases increase the number of limitations in ADL, they do not necessarily entail more formal LTC.The remainder of this article is organized as follows: Sect. LTC refers to the care offered to an elderly in need of assistance in ADL. Depending on the country, the assessment of LTC needs relies on different approaches and recent reforms affect the recognized care levels . NonetheFrance, Germany and Belgium share common characteristics in their LTC policy. In France, the LTC expenses are financed by both the government and private insurance. The State distributes a benefit named “Allocation Personnalisée d’Autonomie” to elderly over 60 years in need of LTC regardless of their wealth , 30. TheConsidering the Mediterranean countries, we note similarities in the systems of Spain, Italy and Greece. Common characteristics include the scarce development of private health insurance solutions and the important place of the help from family members , 27, 62.Sweden and Denmark share analogous LTC schemes with both of them offering universal tax-financed coverage to the whole population. The major characteristic of Scandinavian LTC schemes is to ensure that everyone has equal access to care services irrespective of wealth status or place of residence . In SwedCentral Eastern European countries such as the Czech Republic, Estonia and Slovenia are characterized by a rather low level of LTC services, little regulation by unified laws and high reliance on families. In Czechia, the LTC system is organized through residential, home and community services as well as hospitals for acute care . Based oFinally, we separately discuss the case of Austria and Switzerland. The LTC system in Austria is surely one of the most developed within the European Union. It covers the whole population, but supplementary benefits are subject to means test. Social insurance pays for a cash care allowance “Pflegegeld” where the amount depends on the number of hours of care required varying along seven levels. Further, a 24-h care support benefit is available for those receiving at-home care under means-test conditions. The system is tax-based and managed at the federal and regional levels . Despiteford it .In Table In the following, we derive five conjectures hypothesizing on the characteristics of LTC needs in a sample of European countries. Due to the existing heterogeneity in regulation and in the availability of LTC services, the European continent is a perfect candidate for such study. Taking a cross-country view can provide stronger support to conclusions. The need of LTC is assessed by the measurement of reporting limitations in ADL along the Katz scale. Further, we consider the reporting on the usage of formal LTC services. In our empirical study, we are able to assess these measures throughout selected countries n et al., 78, 97)n et al..In the United States, spouses are often the first provider of at-home care . In caseThe educational level and the wealth status are often considered as a proxy of the social class of an individual. Freedman et al. bring evBoth (a) the probability to report ADL limitations and (b) the probability to report formal LTC usage are significantly affected by demographic  and social factors .Conjecture 1: Pathologies For a long time, mental and physical diseases have been said to strongly impact healthy limitations [tations , 48, 55 tations  find thatations , discusstations  suggest tations , 71, 95)tations , where nMedical factors  have a strong effect on (a) the probability to report ADL limitations and (b) the probability to report formal LTC usage.Conjecture 2: LTC schemes Our third conjecture directly follows from the discussion in Sect. Both (a) the probability to report ADL limitations and (b) the probability to report formal LTC usage significantly differ by types of LTC schemes. Conjecture 3: Types of ADL limitations The scale by[scale by determinscale by. Based oscale by, 67. Whiscale by, only liscale by. Iwarssoscale by report rscale by.The probabilities to report limitations along types of ADL are differently affected by demographic, social and medical factors.Conjecture 4: Formal LTC usage Formal LTC corresponds to professional help provided to an elderly in need of assistance with ADL. These services are distinguished between personal care delivered by nurses and domestic tasks provided by non-medical staff [l staff , 105. Fol staff , about 9l staff , 59. Furl staff .The probabilities to report formal LTC usage along personal care and domestic tasks are differently affected by demographic, social and medical factors.Conjecture 5: To explore Conjectures 1 to 5, we rely on econometric models applied on the records of the Survey of Health, Ageing and Retirement in Europe (SHARE). In Sect. age, gender, body mass index (BMI), smoking habits (daily smoker) and country of residence are typical demographic factors. The survey also contains information on the number of limitations in ADL an elderly has. In our study, we only consider ages from 65 to 99 years, a range where most dependent elderly are found [The SHARE dataset provides information on a representative sample of individuals aged 50 years and over living at home . Covering twenty-seven European countries, this study is re-conducted every two years and has registered six waves over the period from 2004 to 2018. The records are summarized in modules. Eight modules report original respondents’ answers on behavioral risks, children, consumption attitude, demographics, employment, pensions, peak flow, health care and medical assessment. The other three modules contain generated variables for correspondence to international classification standards on physical and mental health, on education and on social network information. The data collection process is managed by local universities that mandate professional polling firms. The process is broken down into two parts: computer-aided personal interviews (CAPI) and paper and pencil medical questions. In the first part, the elderly is assisted by a purpose-trained employee for reporting answers and measuring health indicators such as grip strength and blood pressure. In the second part, the interviewee has to fill in a form treating more personal questions including pathologies.e found . With ree found , i.e. unpartner in household for identifying the type of household, i.e. single- and two-persons households. We observe that this factor is highly correlated with the marital status that we do not consider in our sample. Next, we consider the variable of having children and we include it as a binary  response. Given the substantial difficulties in adding information on the distance to the closest child and the presence of women among children, we exclude them from our study. We introduce the wealth status by considering the financial capacity to make ends meet, categorized among four levels, i.e. easily, fairly easily, with some difficulty and with great difficulty. We account for the individuals’ education level by using the international standard classification of education (ISCED-97) defined by the UNESCO. The SHARE data records the seven levels of the ISCED-97 scale as well as two other classes (persons still studying and others). In our approach, we eliminate individuals with entries in the class “still studying” and “others” representing less than 2% of the data. Further, we cluster the ISCED-97 entries into three groups. The primary education consists in pre-primary and basic education. The secondary education corresponds to the lower, upper and post-secondary education, while the tertiary education contains the first and second stage of tertiary education [Regarding the socio-related variables, we first construct a variable ucation .mental diseases variable is a binary variable that takes the value of one when at least one “yes” appears in the responses to Alzheimer, dementia and emotional disorders. We also consider separately the diagnosis of Parkinson disease and cancer. Positive responses to hip and femoral fractures, rheumatoid arthritis, osteoarthritis and other fractures are gathered through the musculoskeletal system diseases variable. The other physicals diseases variable, namely, heart attack, stroke, diabetes, chronic lung disease, cataracts and chronic kidney represent the last cluster.Finally, we consider the physical and mental health status by constructing five medical factors based on the respondents’ answers to the medical questions “Doctor told you had: ...”. This approach is close to the one used in for repoOur study focuses on the latest wave (wave 6) published in 2018 that contains answers from Demographic, social and medical factors Table Regarding the social factors, 60% report living with their partner, 90% have children and about 65% are found in the mid-high and high wealth status classes. More than 70% have at least a secondary education background. When considering the dependent population, the main differences arise from the lower share reporting to have their partner in the household (46.6%), from the higher shares in the low (16.2%) and mid-low (30.9%) wealth status classes and from the lower share with tertiary education (12.6%). Finally, when considering medical factors (multiple diseases can be reported), few autonomous individuals report having mental, Parkinson or cancer diseases. Overall, the shares of elderly reporting musculoskeletal system (30.0%) and other physical (38.3%) diseases is significantly higher. We observe higher shares for all diseases when considering the dependent population: more than half announce musculoskeletal system (54.4%) and other physical (63.8%) diseases; 21.1% present mental diseases, 4.5% and 7.5% report Parkinson and cancer diseases, respectively. These findings give first insights on the difference between the autonomous and the dependent populations. In fact, individuals that report limitations in ADL are, in comparison to the autonomous population, older, with a higher BMI and more to live alone. Expectedly, they report more diseases highlighting the importance of considering pathologies when discussing ADL limitations.Table e, e.g., ). While Types of ADL limitations Among the 3 931 elderly reporting limitations in ADL, we present their distribution along the six ADL in Table Formal LTC usage In Table In Sect. Explanatory variables We are interested in understanding the effect of various factors on the probability to report limitations in ADL and on the probability to report formal LTC. For this purpose, we consider the demographic, social and medical factors introduced in Sect. AG) is a numeric variable running from 65 to 99 years. Further, we account for nine binary variables as follows. Four sociodemographic variables indicate whether the respondent is a man or a woman (GE), has ever smoked daily (SM), is living with a partner in the same household (HH) and has children (CH). Five medical factors indicate whether the respondent has mental (MD), Parkinson (PA), cancer (CR), musculoskeletal system (MS) or other physical diseases (PD). In these variables, we chose the “no” answer respectively “male” for GE as the baseline category. Choosing “no” for the baseline allows for a direct interpretation of the “yes” category, i.e. having a certain disease, smoking habit, partner in household or children. Finally, we consider four sociodemographic categorical variables giving information on the respondent’s body mass index (BM), wealth status (WS), education level (ED) and country of residence’s LTC scheme (SC). The range of values taken by the categorical variables are discussed in Sect. Since our objective is to develop models explaining the effect of the above variables and not to make a prediction, we keep all variables in each model and study their statistical significance. However, to avoid too complex models, we only consider relevant interactions that improve our model along the Bayesian information criterion (BIC) values using a backward step-wise selection algorithm and present the detailed results of this approach in Table Model selection To investigate the probability to report limitations in ADL, we define six binary variables i refers to the j is k is logit function, the probit model assumes a quantile of the standard normal distribution as link function. For comparison, we also consider a linear regression model. To decide which model yields the best fit, we apply four performance measures. They are the log-likelihood, the deviance, the in-sample area under the curve (AUC) and AUC based on 5-fold cross-validation. Better models present higher log-likelihood and AUC but lower deviance. For selecting the best model, we consider both the probability to report at least one limitation in ADL, i. We report the performance measures in both cases in Table in-sample AUC from 0.7883 , these methods differ through the link function used to relate the dependent variable to the independent variables. While the logistic model uses the entclass1pt{minimaSpecification of the models Following on the above discussion, we introduce two models to study the probability to report ADL limitations. In model  o o4) on tn models  is basedn models  and (4) n models . In addin models . In the Following the results presented in Table Conjecture 1a When considering the results obtained for model .Conjecture 3a In our analysis of the LTC scheme’s effect on the probability to report limitations in ADL, we take Switzerland (“none”) as the baseline for comparison. Given that Switzerland has not developed any particular scheme, it is the perfect reference candidate [ndidate . From thConjecture 4 Our fourth conjecture investigates on potential differences existing along ADL types. For all the types of ADL, the probability to report limitations increases at higher ages, for females and for a lower wealth status as well as for elderlies with mental, Parkinson, cancer, musculoskeletal system and other physical diseases. However, we note differences in the other factors. For example, persons defined as moderately obese have difficulties with dressing, bathing and getting in and out of bed while that characteristic is not significant in walking, eating and toileting. Severely obese persons do not present a significant limitation with eating while very severely obese significantly infer assistance with all activities. Detailing limitations by type of ADL also reveals that the presence of the partner in the household reduces the probability to report limitations with bathing while it has no significant effect on the other activities. Another interesting result comes from the education level. Only persons having a tertiary level of education show a lower probability to report difficulties with walking and bathing activities . FinallBelow we comment on the results displayed in Table Conjecture 1b The results from model  provide some data on elderly reporting limitations in ADL and usage of professional services. Our study does not include wave 3 since this wave has a completely different design and purpose than the other waves. In fact, wave 3 provides a retrospective view on participants’ whole life and uses a different set of questions [N of available observations in each wave. Note that the sample size differs throughout the waves, impacting among other the power of our statistical analysis. The detailed results when applying models  solutions that cover observable costs. Further, by knowing that the presence of the partner in the household significantly reduces the usage of formal LTC essentially for domestic tasks, relying only on informal care is not reasonable. Indeed, LTC costs related to personal care delivered by professional caregivers is incompressible and represents an expensive part of LTC. Finally, by observing a significant effect of the specific LTC scheme on the usage of services, our work gives important insights on public-private interactions for LTC financing and for policymaking. In fact, based on our findings, less LTCI crowding out effects are to be expected in countries with family care and subsidiary LTC schemes when compared to countries with State responsibility LTC schemes.Limitations of the present study Our study is subject to a set of limitations. First, the SHARE dataset solely accounts for elderly cared for at home and neglects persons cared for in an institution. Accounting for the latter would bring stronger evidence on the impact of medical factors on ADL limitations since they often report mental diseases. Second, important limitations arise when using a survey setup. As mentioned in Sect. In this paper, we assess the probability to report ADL limitations and the probability to use formal LTC among elderly aged From a probit regression model, we find that the age, the gender, the BMI, the presence of the partner in the household, the wealth status, the education level and the pathology highly influence the reporting of ADL limitations. First, women aged above 80 years report more limitations than men. Second, while we observe no effect of having children on the reported functional limitations, this result is reversed when a partner lives in the household. Third, persons with higher wealth and higher education level report lower difficulties with ADL. Thereafter, our findings show that pathologies importantly increase functional limitations. However, the effect is lower for people diagnosed with cancer when compared to mental diseases or Parkinson. Finally, the LTC policy of the country of residence has little influence on the reporting.Based on a logit regression model, we study the covariates influencing the probability to report formal LTC usage. In comparison to functional limitations that can be observed, the usage of professional care is subject to the availability of informal care. In our results, we find that older women appear to require more formal care than men. While some socio-related factors such as the BMI, the smoking habits and the wealth status have no influence, we observe a lower probability for men when there is a partner in the household. This observation highlights the importance of the spouse in providing informal LTC and limiting the demand of professional care. From the pathologies, we find that mental diseases and Parkinson have the highest effect on using formal LTC. In comparison to other diseases, they often require qualified caregivers. Our results also highlight that a cancer diagnosis does not entail significantly more formal care. Further, we observe that elderly living in family care schemes report significantly less formal care usage than those from other cultural backgrounds or countries with different policy arrangements. Finally, by distinguishing formal care along personal and domestic tasks, we find that the partner in the household mostly helps in reducing the probability to demand professional help with domestic tasks.The SHARE dataset has enabled us to identify functional limitations in ADL and formal LTC usage in a comprehensive cross-country study. While offering an extensive analysis along demographic, social, medical and policy factors, various streams of research could extend the present study. First, the delivery of informal care by relatives surely needs more investigation. For example, providing informal care can also be linked to moral hazard issues in particular linked to the expected inheritance from children . Second


All-trans retinoic acid (ATRA) is known to induce complete remission of acute promyelocytic leukemia (APL) and its use has significantly improved the cure rate of APL. However, ATRA also causes side effects such as differentiation syndrome or intracranial hypertension. In our case, the patient was diagnosed with APL and developed hearing loss thrice while being treated with ATRA. Therefore, we reduced the dose of ATRA instead of stopping it altogether and administered dexamethasone to the patient. A hearing test performed thereafter revealed recovery of hearing. No recurrence of hearing loss occurred after prednisolone and ATRA were combined in the maintenance phase. In conclusion, ATRA-associated hearing loss is reversible, and it is not necessary to stop ATRA. We recommend completion of a randomized clinical trial using dexamethasone in combination with ATRA to prevent hearing loss caused by ATRA. Acute promyelocytic leukemia (APL) is a type of acute myeloid leukemia (AML). The cure rate of APL has improved remarkably since the introduction of all-trans retinoic acid (ATRA) as a treatment . HoweverThis report was approved by the institutional review board (IRB) of Yeungnam University Hospital (IRB No: YUMC 2020-07-037). Written informed consent was obtained from the patient and guardians for the publication of this case report and the accompanying images. The patient was a 13-year-old boy who presented with fever, leukopenia, and thrombocytopenia. Bone marrow aspiration and examination revealed hypercellular marrow with 89% of the promyelocytes being abnormal, and PCR showed promyelocytic leukemia (PML)/retinoic acid receptor, alpha (RARα) positivity. Based on these findings, a diagnosis of APL was made .2/day) was administered immediately after APL was suspected; chemotherapy was started according to the modified AIDA-2000 protocol. Dexamethasone was added for prophylaxis of DS. Brain MRI was performed because the patient developed headache 2 days after the start of ATRA treatment; it revealed no bleeding or mass. On physical examination, papilledema was also not observed. After the induction phase, the patient suddenly developed tinnitus of the left ear. Pure tone audiometry (PTA), speech audiometry, impedance audiometry, and tinnitogram did not reveal any abnormality (2/day) was started 1 week later.Treatment with ATRA  was used to prevent ATRA-induced ototoxicity when using ATRA (25 mg/m2). Currently, the third maintenance phase is underway and ototoxicities such as tinnitus have not recurred.Tinnitus recurred when ATRA was restarted in the third consolidation period; therefore, ATRA was withdrawn and dexamethasone was restarted. Consequently, tinnitus resolved in the same manner as before. A bone marrow aspiration test performed after the consolidation period showed normal findings. In the maintenance period, prednisolone  rate of up to 50% in patients with APL [APL, a subtype of AML, is caused by the fusion of the with APL . Despitewith APL . Hence, ATRA is now recognized as the major component of treatment for APL patients; however, it also has side effects. The most commonly reported side effect of ATRA use is DS. However, hearing impairment during ATRA treatment has been rarely reported. Fujiki et al. reported the case of a 12-year-old female patient with APL who developed hearing impairment during ATRA treatment . This paLibien et al. insist that the cause of hearing loss is ATRA-related hearing impairment associated with increased intracranial pressure (IICP) . Cerebro2) during the maintenance period. The cause of hearing impairment was thought to be an imbalance between internal and external lymph due to IICP, as Fujiki et al. insisted. Since ICP was not measured through lumbar puncture, it is difficult to describe a clear causal relationship between hearing impairment and IICP. Nevertheless, the possibility is high because the findings suggested IICP, for example headache before the development of hearing impairment.In our case, the patient developed hearing impairment after headache during the induction phase. PTA showed significantly reduced hearing in the left ear at 250, 500, and 1000 Hz; this finding was similar to that in the previously mentioned case in which the patient’s hearing improved after treatment with dexamethasone . HoweverDS could also cause hearing loss. DS is characterized by clinical symptoms, such as fever, dyspnea, weight gain, hypotension, or acute kidney failure. Montesinos et al. reported that 24.8% of patients with APL treated using ATRA developed DS . DS indu2 in adults, but a reduced dose of 25 mg/m2 in children, ATRA is often recommended for pediatric patients because of their greater risk of developing intracranial hypertension [Recent experts recommend ATRA 45 mg/mrtension .ATRA-induced SNHL is a rare but possible side effect. If SNHL develops in a patient treated with ATRA, it is necessary to evaluate hearing impairment by conducting PTA and rule out intracranial hemorrhage by performing CT or MRI. Steroids can be used to manage inflammation, and could be used as prophylaxis if SNHL recurs.


Hearing loss is highly prevalent among older adults and has deleterious effects on health. However, its association with physical functioning is not well defined. We investigated the cross-sectional association between hearing and physical function in 3,339 community-dwelling participants  of the Atherosclerosis Risk in Communities Study (ARIC). Hearing was measured by pure-tone average ([dB]) of 4 frequencies  and physical function was measured using the short physical performance battery (SPPB), which consisted of 3 performance-based tests  each scored ranging from 0-4, resulting in a total possible score of 0-12 . We estimated the association between hearing and physical function using continuous scores for each component of the battery, and the overall SPPB score categorized into high [10-12], intermediate [7-9], and low [≤6]) using ordinal logistic regression models. The SPPB scores were reversed for an easier interpretation of the odds ratios (OR). The category with better physical functions was the reference group for each model. After adjustment for demographics and comorbidities, poorer hearing (+10 dB in PTA) was associated with worse physical functioning: OR for lower balance score=1.17, 95% CI ; OR for lower gait speed score=1.15, 95%CI ; OR for lower chair stand score=1.07, 95% CI ; and OR for lower overall SPPB category=1.15, 95%CI . Hearing loss is associated with poorer physical functioning, highlighting the potentially negative impact of hearing loss on mobility at older ages.