Hearing loss increases all-cause and cardiovascular mortality in middle-aged and older Chinese adults: the Dongfeng-Tongji Cohort Study.

We aimed to investigate the association between hearing loss and all-cause and cardiovascular disease (CVD) mortality, and whether the relationship could be modified by chronic conditions in middle-aged and older Chinese adults. We selected 18,625 participants who underwent audiometry in 2013 from the Dongfeng-Tongji Cohort conducted in China, and followed them until December 2018. Hearing loss was grouped as normal, mild, and moderate or severe by pure-tone hearing threshold at speech (0.5, 1, and 2 kHz) and high frequency (4 and 8 kHz). We applied Cox regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and CVD mortality. Among the 18,625 participants, the mean age was 64.6 (range: 36.7-93.0) years, and 56.2% were women. A total of 1185 died, with 420 CVD deaths during a mean follow-up period of 5.5 years. The adjusted HR for all-cause and CVD mortality increased gradually with the increasing hearing threshold (All p for trend < 0.05). Compared to participants with normal hearing at speech frequency, the adjusted HRs (95% CIs) of moderate or severe hearing loss were 1.42 (1.21-1.67), 1.44 (1.10-1.89), and 1.92 (1.21-3.04) for all-cause, CVD, and stroke mortality, respectively. While moderate or severe hearing loss at high frequency was only related to an increased risk of all-cause mortality (HR, 1.60; 95% CI, 1.18-2.17). The associations were generally consistent across subgroups (All p for interaction > 0.05). Additionally, individuals with a combination of moderate or severe hearing loss and occupational noise exposure, diabetes, or hypertension had higher risk of all-cause or CVD mortality, ranging from 1.45 to 2.78. In conclusion, hearing loss was independently associated with an increased risk of all-cause and CVD mortality, in a dose-response manner. Meanwhile, hearing loss and diabetes or hypertension could jointly increase the risk of all-cause and CVD mortality.

Mortality and Cause of Death in Hearing Loss Participants: A Longitudinal Follow-up Study Using a National Sample Cohort.

OBJECTIVE: The purpose of the present study was to estimate the risk of mortality in hearing loss subjects in accordance with the cause of death. STUDY DESIGN: A longitudinal follow up study. SETTING: Data from the Korean National Health Insurance Service-National Sample Cohort were collected from a period between 2002 and 2013. PATIENTS AND INTERVENTION: The 4,606 severe and 1,007 profound hearing loss participants with 40 or more years old were 1:4 matched with control participants, respectively, for age, sex, income, and region of residence. The causes of death were grouped into 12 classifications. MAIN OUTCOME MEASURES: The ratio of mortality was compared between the hearing loss and control group using a χ test or Fisher's exact test. In a Cox-proportional hazard model, age, sex, income, region of residence, and past medical histories were considered confounders. RESULTS: The severe and profound hearing loss groups showed 4.07 (95% CI = 3.71-4.46, p < 0.001) and 4.22 times (95% CI = 3.52-5.05, p < 0.001) higher mortality ratios in the adjusted models, respectively. Both the severe and profound hearing loss groups showed higher mortality by infection, neoplasm, trauma, and metabolic, mental, circulatory, respiratory, and digestive diseases than control groups (p < 0.05). Among various causes of death, death by trauma revealed the highest odds ratios in both the severe and profound hearing loss groups. CONCLUSION: Hearing loss was associated with a significant increase in mortality.

Hearing loss, family status and mortality - Findings from the HUNT study, Norway.

Hearing loss as well as being single has been associated with an increased risk of all-cause mortality. The purpose of the study is to assess whether being single or childless moderates the elevated risk of mortality in hearing impaired. The Nord-Trøndelag hearing Loss Study examined 50,462 persons above 20 years of age during 1996-1998. The Norwegian Cause of Death Registry was used to identify deaths until 2016. Data on marital status was obtained from the Norwegian Population Registry. Hearing loss was defined as the pure-tone average (0.5-4 kHz) of hearing thresholds greater than 25 dB hearing level (dB HL) in the better ear. Associations between hearing loss and mortality risk were estimated using Cox regression after an average follow-up of 17.6 years. Hearing loss was associated with increased risk of all-cause mortality before 75 years of age (hazard ratio [HR] 1.3, 95% confidence interval [CI] 1.2-1.4) and cardiovascular mortality (HR 1.8, 95% CI 1.5-2.1) but not with cancer mortality (HR 1.1, 95% CI 0.9-1.3) or mortality due to injuries (HR 1.4, 95% CI 0.9-2.3). Adjusting for socio-economic characteristics, cardiovascular risk-factors, diseases, and family status, reduced the associations for all-cause mortality (HR 1.1, 95% CI 1.0-1.2) and cardiovascular mortality (HR 1.4, 95% CI 1.2-1.6). The adjusted mortality risk was found to be significantly related to family status. Being divorced raised the mortality risk associated with hearing loss among those below 75 years of age. There was a similar tendency also for being childless, although this was only significant for females. There was also a trend for a lower mortality related to hearing loss in subjects with a well-hearing partner. More focus should be given to those who lack a family when having functional limitations such as hearing impairment.

Death, Depression, Disability, and Dementia Associated With Self-reported Hearing Problems: A 25-Year Study.

Background: Hearing loss in older adults is suspected to play a role in social isolation, depression, disability, lower quality of life, and risk of dementia. Such suspected associations still need to be consolidated with additional research. With a particularly long follow-up, this study assessed the relationship between hearing status and four major adverse health events: death, dementia, depression, and disability. Methods: Prospective community-based study of 3,777 participants aged ≥65 followed up for 25 years. At baseline, 1,289 reported hearing problems and 2,290 reported no trouble. The risk of occurrence of the negative outcomes, including death, dementia, depressive symptoms, disability in activities of daily living (ADL), and instrumental ADL (IADL), was assessed with Cox proportional hazards models. Results: Adjusting for numerous confounders, an increased risk of disability and dementia was found for participants reporting hearing problems. An increased risk of depression was found in men reporting hearing problems. In additional exploratory analyses, such associations were not found in those participants using hearing aids. Mortality was not associated with self-reported hearing loss. Conclusions: Our study confirms the strong link between hearing status and the risk of disability, dementia, and depression. These results highlight the importance of assessing the consequences of treating hearing loss in elders in further studies.

Meta-analysis of adjunctive dexamethasone to improve clinical outcome of bacterial meningitis in children.

BACKGROUND: The current recommended therapies for bacterial meningitis are effective antimicrobial agents and the implementation of childhood vaccination programs. However, the role of adjunctive dexamethasone therapy in bacterial meningitis remains controversial. METHODS: Using meta-analysis, this study aims to investigate the efficacy of adjunctive dexamethasone therapy in bacterial meningitis by comparing it with antibiotic therapy. Documents of randomized controlled trials (RCT) related to the treatment of bacterial meningitis in children with dexamethasone published since the establishment of the databases to December in 2016 were retrieved from the databases of Cochrane Library, Pubmed, MEDLINE, EMBASE, Chinese BioMedical Literature Database, and China National Knowledge Infrastructure. The references in RCT were retrieved by hands at the same time. Full texts of screened documents were searched and given qualitative review, and then, all RCT included were analyzed statistically by using Review Manger 5.3 software. RESULTS: The search yielded 15 studies (2409 children cases), among which 4 fall in grade A and 11 were grade B. The results of meta-analysis have shown that patients who received dexamethasone have significantly lower risks in incidence of hearing loss (OR = 0.68, 95%CI 0.53-0.89, P = 0.004) and severe neurological sequelae (OR = 0.59, 95%CI 0.37-0.95, P = 0.03), but the follow-up mortality is hardly effected (OR = 0.86, 95%CI 0.67-1.10, P = 0.23). CONCLUSIONS: Evidence has proven that the adjunctive administration of dexamethasone is conducive to treating children with bacterial meningitis to a certain extent, to decreasing the possibility of hearing loss and severe neurological sequelae, but has no significant effect on the follow-up mortality.

Vision and hearing impairments, cognitive impairment and mortality among long-term care recipients: a population-based cohort study.

BACKGROUND: Vision and hearing impairments among elders are common, and cognitive impairment is a concern. This study assessed the association of vision and hearing impairments with cognitive impairment and mortality among long-term care recipients. METHODS: Data of 1754 adults aged 65 or older were included in analysis from the Gujo City Long-Term Care Insurance Database in Japan for a mean follow-up period of 4.7 years. Trained and certified investigators assessed sensory impairments and cognitive impairment using a national assessment tool. Five-level scales were used to measure vision and hearing impairments. Cognitive performance was assessed on two dimensions, namely communication/cognition and problem behaviors. We performed logistic regression analysis to estimate odd ratios (ORs) and 95 % confidence intervals (CIs) for the association of vision and hearing impairments with cognitive impairment. Using Cox proportional hazard regression models, we obtained hazard ratios (HRs) for mortality. RESULTS: Of 1754 elders, 773 (44.0 %) had normal sensory function, 252 (14.4 %) vision impairment, 409 (23.3 %) hearing impairment, and 320 (18.2 %) dual sensory impairment. After adjusting for potential cofounders, ORs of cognitive impairment were 1.46 (95 % CI 1.07-1.98) in individuals with vision impairment, 1.47 (95 % CI 1.13-1.92) in those with hearing impairment, and 1.97 (95 % CI 1.46-2.65) in those with dual sensory impairment compared to individuals with normal sensory function. The adjusted HR of overall mortality was 1.29 (95 % CI 1.01-1.65) in individuals with dual sensory impairment and cognitive impairment relative to normal sensory and cognitive functions. CONCLUSIONS: Cognitive impairment was most common in individuals with dual sensory impairment, and those with dual sensory impairment and cognitive impairment had increased mortality.

Muscle strengthening activities and mortality with considerations by hearing sensitivity.

OBJECTIVE: Research demonstrates that hearing impairment is associated with premature all-cause mortality. Emerging work indicates that physical activity is associated with hearing sensitivity and muscle strengthening activities (MSA) are favorably associated mortality in the general population. Whether MSA can promote survival among those with hearing impairment is, at this point, unknown, which was this study's objective. DESIGN: Prospective cohort study using data from the 2003-2006 National Health and Nutrition Examination Survey, with follow-up through 2011. STUDY SAMPLE: 1482 adult (20-85 years) participants comprised the analytic sample. RESULTS: Among the study participants, 152 died over the follow-up period (10.26%; unweighted); the unweighted median follow-up period was 89 months (IQR = 74-98 months). Among adults with moderate or greater hearing loss who achieved the United States Department of Health and Human Services guidelines for MSA (2 + sessions/week), they were at a 71% reduced risk of all-cause mortality (HRadjusted = 0.29; 95% CI: 0.10-0.83; P = 0.02). CONCLUSIONS: MSA may help to prolong survival among those with worse hearing impairment.

Joint Associations of Dual Sensory Impairment and No-Activity Involvement With 1-Year Mortality in Nursing Homes: Results From the SHELTER Study.

BACKGROUND: Concurrent vision and hearing impairment, known as dual sensory impairment (DSI), is associated with increased mortality. We aimed to examine individual and joint associations of DSI and involvement in activities with mortality in a large European nursing home study. METHODS: In total, 2,851 nursing home residents in 59 facilities in eight countries were followed for 1 year in the Services and Health for Elderly in Long TERm Care study. Vision and hearing impairment and average time of involvement in activities were assessed by trained research staff using the interRAI Long Term Care Facilities. Association between DSI and 1-year all-cause mortality was examined using Cox proportional hazards models adjusted for age, sex, facility, diagnoses of coronary heart disease and diabetes mellitus, self-rated health, end-stage disease, and functional and cognitive status. The modifying effect of involvement in activities on the association was investigated by the additive hazard model. RESULTS: DSI, defined as moderate to severe impairment in both senses, was independently associated with a 35% increased risk of 1-year mortality compared with non-DSI. Residents with DSI who were involved in activities did not have higher mortality, while residents with DSI who were not involved in activities had 51% higher mortality than non-DSI residents who were involved in activities, equivalent to approximately 209 additional deaths per 1,000 person-years (p = .012) due to the interaction between DSI and no involvement in activities. CONCLUSIONS: DSI is associated with increased mortality at nursing homes when combined with no involvement in activities.

Hearing-aid use and long-term health outcomes: Hearing handicap, mental health, social engagement, cognitive function, physical health, and mortality.

OBJECTIVE: To clarify the impact of hearing aids on mental health, social engagement, cognitive function, and physical health outcomes in older adults with hearing impairment. DESIGN: We assessed hearing handicap (hearing handicap inventory for the elderly; HHIE-S), cognition (mini mental state exam, trail making, auditory verbal learning, digit-symbol substitution, verbal fluency, incidence of cognitive impairment), physical health (SF-12 physical component, basic and instrumental activities of daily living, mortality), social engagement (hours per week spent in solitary activities), and mental health (SF-12 mental component) at baseline, five years prior to baseline, and five and 11 years after baseline. STUDY SAMPLE: Community-dwelling older adults with hearing impairment (N = 666) from the epidemiology of hearing loss study cohort. RESULTS: There were no significant differences between hearing-aid users and non-users in cognitive, social engagement, or mental health outcomes at any time point. Aided HHIE-S was significantly better than unaided HHIE-S. At 11 years hearing-aid users had significantly better SF-12 physical health scores (46.2 versus 41.2; p = 0.03). There was no difference in incidence of cognitive impairment or mortality. CONCLUSION: There was no evidence that hearing aids promote cognitive function, mental health, or social engagement. Hearing aids may reduce hearing handicap and promote better physical health.

Association of hearing impairment and mortality in older adults.

BACKGROUND: Hearing impairment (HI) is highly prevalent in older adults and is associated with social isolation, depression, and risk of dementia. Whether HI is associated with broader downstream outcomes is unclear. We undertook this study to determine whether audiometric HI is associated with mortality in older adults. METHODS: Prospective observational data from 1,958 adults ≥70 years of age from the Health, Aging, and Body Composition Study were analyzed using Cox proportional hazards regression. Participants were followed for 8 years after audiometric examination. Mortality was adjudicated by obtaining death certificates. Hearing was defined as the pure-tone average of hearing thresholds in decibels re: hearing level (dB HL) at frequencies from 0.5 to 4kHz. HI was defined as pure-tone average >25 dB HL in the better ear. RESULTS: Of the 1,146 participants with HI, 492 (42.9%) died compared with 255 (31.4%) of the 812 with normal hearing (odds ratio = 1.64, 95% CI: 1.36-1.98). After adjustment for demographics and cardiovascular risk factors, HI was associated with a 20% increased mortality risk compared with normal hearing (hazard ratio = 1.20, 95% CI: 1.03-1.41). Confirmatory analyses treating HI as a continuous predictor yielded similar results, demonstrating a nonlinear increase in mortality risk with increasing HI (hazard ratio = 1.14, 95% CI: 1.00-1.29 per 10 dB of threshold elevation up to 35 dB HL). CONCLUSIONS: HI in older adults is associated with increased mortality, independent of demographics and cardiovascular risk factors. Further research is necessary to understand the basis of this association and whether these pathways might be amenable to hearing rehabilitation.

Late effects in survivors of childhood CNS tumors treated on Head Start I and II protocols.

BACKGROUND: Due to the devastating late effects associated with cranial irradiation in young children with central nervous system (CNS) tumors, treatment for these patients has evolved to include the use of intensive chemotherapy to either avoid or postpone irradiation. While survival outcomes have improved, late effects data in survivors treated on such regimens are needed. OBJECTIVE: This multi-institutional study comprehensively describes late effects in survivors treated on the Head Start I/II protocols. METHODS: Survivors of CNS tumors treated on Head Start I/II protocols were enrolled. Late effects data were collected using a validated parent-report questionnaire. Social, emotional, and behavioral functioning and quality of life were assessed using parent-report on the BASC-2 and CHQ-PF50 questionnaires. RESULTS: Twenty-one survivors (medulloblastoma = 13, sPNET = 4, ATRT = 1, ependymoma = 3) were enrolled. Ten (48%) were irradiation-free. Late effects (frequency; median time of onset since diagnosis) included ≥ grade III hearing loss (67%; 3.9 years), vision (67%; 4.1 years), hypothyroidism (33%; 4 years), growth hormone (GH) deficiency (48%; 4.7 years), dental (52%; 7.1 years), and no cases of secondary leukemia. Irradiation-free (vs. irradiated) survivors reported low rates of hypothyroidism (0/10 vs. 7/11; P = 0.004) and GH deficiency (2/10 vs. 8/11; P = 0.03). The BASC-2 and CHQPF-50 mean composite scores were within average ranges relative to healthy comparison norms. Neither age at diagnosis nor irradiation was associated with these scores. CONCLUSIONS: Irradiation-free Head Start survivors have lower risk of hypothyroidism and GH deficiency. Secondary leukemias are not reported. With extended follow-up, survivors demonstrate quality of life, social, emotional, and behavioral functioning within average ranges.

Cost-effectiveness analysis of cochlear dose reduction by proton beam therapy for medulloblastoma in childhood.

BACKGROUND: The aim of this study is to evaluate the cost-effectiveness of proton beam therapy with cochlear dose reduction compared with conventional X-ray radiotherapy for medulloblastoma in childhood. METHODS: We developed a Markov model to describe health states of 6-year-old children with medulloblastoma after treatment with proton or X-ray radiotherapy. The risks of hearing loss were calculated on cochlear dose for each treatment. Three types of health-related quality of life (HRQOL) of EQ-5D, HUI3 and SF-6D were used for estimation of quality-adjusted life years (QALYs). The incremental cost-effectiveness ratio (ICER) for proton beam therapy compared with X-ray radiotherapy was calculated for each HRQOL. Sensitivity analyses were performed to model uncertainty in these parameters. RESULTS: The ICER for EQ-5D, HUI3 and SF-6D were $21 716/QALY, $11 773/QALY, and $20 150/QALY, respectively. One-way sensitivity analyses found that the results were sensitive to discount rate, the risk of hearing loss after proton therapy, and costs of proton irradiation. Cost-effectiveness acceptability curve analysis revealed a 99% probability of proton therapy being cost effective at a societal willingness-to-pay value. CONCLUSIONS: Proton beam therapy with cochlear dose reduction improves health outcomes at a cost that is within the acceptable cost-effectiveness range from the payer's standpoint.

Outcomes of infants born at 22 and 23 weeks' gestation.

OBJECTIVE: To provide instructive information on death and neurodevelopmental outcomes of infants born at 22 and 23 weeks' gestational age. METHODS: The study cohort consisted of 1057 infants born at 22 to 25 weeks in the Neonatal Research Network, Japan. Neurodevelopmental impairment (NDI) at 36 to 42 months' chronological age was defined as any of the following: cerebral palsy, hearing impairment, visual impairment, and a developmental quotient <70. A systematic review was performed by using databases of publications of cohort studies with neonatal and neurodevelopmental outcomes at 22 and 23 weeks. RESULTS: Numbers and incidences (%) of infants with death or NDI were 60 (80%) at 22 weeks and 156 (64%) at 23 weeks. In logistic regression analysis, gestational ages of 22 weeks (odds ratio [OR]: 5.40; 95% confidence interval [CI]: 2.48-11.76) and 23 weeks (OR: 2.14; 95% CI: 1.38-3.32) were associated with increased risk of death or NDI compared with 24 weeks, but a gestational age of 25 weeks (OR: 0.65; 95% CI: 0.45-0.95) was associated with decreased risk of death or NDI. In the systematic review, the medians (range) of the incidence of death or NDI in 8 cohorts were 99% (90%-100%) at 22 weeks and 98% (67%-100%) at 23 weeks. CONCLUSIONS: Infants born at 22 and 23 weeks' gestation were at higher risk of death or NDI than infants at born at 24 weeks. However, outcomes were improved compared with those in previous studies. There is a need for additional discussions on interventions for infants born at 22 or 23 weeks' gestation.

Short- and long-term consequences of hypotension in ELBW infants.

BACKGROUND: Hypotension affects close to half of all ELBW infants, yet an agreement on its definition is still lacking. Despite the fact that neonatal hypotension may be a risk factor for neurologic impairment, there is a paucity of data on the impact of low blood pressure (BP) in extremely low birth weight (ELBW) infants weighing below 1000 g on neuro-developmental outcome. OBJECTIVES: Explore the relationship between blood pressure in the first 72 hours of life, perinatal factors, morbidity, and mortality in ELBW infants. Compare neuro-sensory outcome in ELBW infants with and without symptomatic hypotension. METHODS: We reviewed the outcome for all 156 infants with a birth weight <1000 g admitted to the neonatal intensive care unit covering the time period 1998 to 1999. Infants who received fluid pushes and/or pressors during the first 72 hours of life in an attempt to increase blood pressure were regarded as "symptomatic" or "treated infants"; the others were designated "non-treated infants." Follow-up at 20 months corrected age included neurologic status, Bayley motor/mental evaluation, plus tests of vision and hearing. Statistical analysis was by SPSS 11.0. Univariate and multivariate analyses were conducted to determine morbidities associated with symptomatic hypotension. RESULTS: A total of 59 infants (mean BW 714 +/- 154 g; GA 24.9 +/- 1.7 weeks) required BP support; 97 infants (mean BW 768 +/- 141 g; GA 26.1 +/- 1.9 weeks) received no BP support. The groups had similar race, gender, delivery mode, and maternal socioeconomic status. Thirty-five (22%) infants died, including 20 who received BP support. There were more infants with severe IVH (grade III/IV), 19% versus 2%, and the mortality was greater, 34% versus 16%, in those infants who received BP support. Of the 121 survivors, 110 (91%) had complete follow-up evaluations. Multivariate analysis controlling for SES and neonatal morbidity revealed that symptomatic hypotension is associated with delayed motor development (-6.0; SE 3.1) and hearing loss (O.R. 8.9; CI 0.92-86.3). CONCLUSIONS: Symptomatic hypotension in ELBW infants in the first 72 hours of life is associated with significant short-term and long-term morbidity. Infants with symptomatic hypotension are more likely to have delayed motor development, hearing loss, and death.

WR-2721 (Amifostine) ameliorates cisplatin-induced hearing loss but causes neurotoxicity in hamsters: dose-dependent effects.

Chemoprotective agents reduce the toxic side effects of chemotherapy agents such as cisplatin. The conventional belief is that the chemoprotective agent WR-2721 (Amifostine), while protecting against most cisplatin-induced side effects, does not protect against cisplatin-induced ototoxicity (i.e., hearing loss). There is no knowledge, however, about the efficacy of high doses of WR-2721 (WR) in possibly protecting against cisplatin-induced ototoxicity. Thus, the dose-dependent effects of WR in possibly ameliorating cisplatin-induced ototoxicity were investigated. Hamsters were given a series of 5 cisplatin injections (3 mg/kg/injection once every other day, i.p.) either alone or in combination with 18, 40, 80, or 400 mg/kg/injection of the rescue agent WR ( n = 5 or 10/group). Other groups received either 80 mg/kg/injection WR alone ( n = 5) or were untreated ( n = 14). Ototoxicity was assessed by auditory brain stem responses (ABR). WR provided dose-dependent rescue from cisplatin's ototoxicity with no protection at the low dose of 18 mg/kg, moderate protection at 40 mg/kg, and nearly complete protection at 80 and 400 mg/kg. However, WR doses of 40 mg/kg or higher caused neurotoxicity as evidenced by prolongations in the ABR's interpeak latencies. Thus, high doses of WR provided the beneficial effect of protecting against cisplatin-induced ototoxicity, but had the harmful side effect of neurotoxicity. Previous failures to find chemoprotection from cisplatin-induced ototoxicity were likely due to the use of WR doses that were too small. The clinical implications of the beneficial and harmful effects of high doses of WR are discussed.