Normal Weight Central Obesity is a Poor Prognostic Factor for Sudden Sensorineural Hearing Loss.

OBJECTIVES: To investigate the role of normal weight central obesity (NWCO) in the prognosis of sudden sensorineural hearing loss (SSNHL). METHODS: We retrospectively investigated 807 cases of SSNHL from January of 2008 to August of 2019 from the Department of Otorhinolaryngology at Kaohsiung Medical University Hospital in southern Taiwan. We analyzed the association between overweight and obesity, NWCO, and the prognosis of SSNHL. The demographic and clinical characteristics, audiometry results, and outcomes were also reviewed. RESULTS: The nonobese (body mass index [BMI] < 24 kg/m2) and overweight and obese groups (BMI ≥ 24 kg/m2) comprised 343 (42.50%) and 464 (57.50%) patients, respectively. The favorable prognosis rates in the nonobese and the overweight and obese groups were 45.48% and 45.91%, respectively, without a significant difference (P = .9048). Multivariate logistic regression revealed that BMI (adjusted odds ratio [aOR] = 1.00, 95% CI = 0.948-1.062, P = .9165) was not significantly associated with SSNHL recovery. The normal weight noncentral obesity (NWNCO) and NWCO groups comprised 266 (77.55%) and 77 (22.45%) patients, respectively, and had favorable prognosis rates of 48.50% and 35.06%, respectively. The difference between the groups was significant (P = .0371). Multivariate logistic regression analysis revealed that NWCO (aOR = 2.51, 95% CI = 1.292-5.019, P = .0075) was significantly associated with SSNHL recovery. CONCLUSIONS: NWCO may significantly affect the prognosis of SSNHL.

Correction: Dashboard With Bump Charts to Visualize the Changes in the Rankings of Leading Causes of Death According to Two Lists: National Population-Based Time-Series Cross-Sectional Study.

[This corrects the article DOI: 10.2196/42149.].

Predictive Factors and Audiometric Outcome Comparison Between Titanium Prosthesis and Autologous Incus in Traumatic Ossicular Injury.

OBJECTIVES: To investigate the etiology and ossicular pathology of traumatic ossicular injury in Taiwan and examine the hearing outcomes and predictive factors between the titanium prosthesis and autologous incus groups. METHODS: We retrospectively analyzed patients with traumatic ossicular injury from 2011 to 2020 in Taiwan. Patients were divided into the titanium or autologous group according to the surgical materials used. The audiometric outcomes and predictive factors of ossiculoplasty were analyzed between groups. RESULTS: Twenty patients with ossicular chain discontinuity were enrolled (8 in the titanium group and 12 in the autologous group). The postoperative hearing threshold (26.6 ± 8.9 dB) and air-bone gap (10.3 ± 5.6 dB) improved significantly compared with the preoperative hearing threshold (50.7 ± 13.3 dB) and air-bone gap (29.9 ± 11.0 dB). The improvements in the hearing threshold and air-bone gap were not significantly different between the titanium and autologous groups. Our patients presented an improvement in hearing restoration with 65% closure of the air-bone gap in 0 to 10 dB range and 30% in 11 to 20 dB range, without sensorineural hearing loss during surgery. Univariate regression analysis revealed that vertigo, benign paroxysmal positional vertigo, and temporal bone fracture may serve as negative factors influencing the air-bone gap gain. CONCLUSIONS: Ossiculoplasty with both titanium prosthesis and autologous materials demonstrated favorable hearing recovery in traumatic ossicular injury. Vertigo, benign paroxysmal positional vertigo, and temporal bone fracture may serve as negative predictive factors of the hearing benefit after surgery.

Dashboard With Bump Charts to Visualize the Changes in the Rankings of Leading Causes of Death According to Two Lists: National Population-Based Time-Series Cross-Sectional Study.

BACKGROUND: Health advocates and the media often use the rankings of the leading causes of death (CODs) to draw attention to health issues with relatively high mortality burdens in a population. The National Center for Health Statistics (NCHS) publishes "Deaths: leading causes" annually. The ranking list used by the NCHS and statistical offices in several countries includes broad categories such as cancer, heart disease, and accidents. However, the list used by the World Health Organization (WHO) subdivides broad categories (17 for cancer, 8 for heart disease, and 6 for accidents) and classifies Alzheimer disease and related dementias and hypertensive diseases more comprehensively compared to the NCHS list. Regarding the data visualization of the rankings of leading CODs, the bar chart is the most commonly used graph; nevertheless, bar charts may not effectively reveal the changes in the rankings over time. OBJECTIVE: The aim of this study is to use a dashboard with bump charts to visualize the changes in the rankings of the leading CODs in the United States by sex and age from 1999 to 2021, according to 2 lists (NCHS vs WHO). METHODS: Data on the number of deaths in each category from each list for each year were obtained from the Wide-ranging Online Data for Epidemiologic Research system, maintained by the Center for Disease Control and Prevention. Rankings were based on the absolute number of deaths. The dashboard enables users to filter by list (NCHS or WHO) and demographic characteristics (sex and age) and highlight a particular COD. RESULTS: Several CODs that were only on the WHO list, including brain, breast, colon, hematopoietic, lung, pancreas, prostate, and uterus cancer (all classified as cancer on the NCHS list); unintentional transport injury; poisoning; drowning; and falls (all classified as accidents on the NCHS list), were among the 10 leading CODs in several sex and age subgroups. In contrast, several CODs that appeared among the 10 leading CODs according to the NCHS list, such as pneumonia, kidney disease, cirrhosis, and sepsis, were excluded from the 10 leading CODs if the WHO list was used. The rank of Alzheimer disease and related dementias and hypertensive diseases according to the WHO list was higher than their ranks according to the NCHS list. A marked increase in the ranking of unintentional poisoning among men aged 45-64 years was noted from 2008 to 2021. CONCLUSIONS: A dashboard with bump charts can be used to improve the visualization of the changes in the rankings of leading CODs according to the WHO and NCHS lists as well as demographic characteristics; the visualization can help users make informed decisions regarding the most appropriate ranking list for their needs.

Ranking of Alzheimer's disease and related dementia among the leading causes of death in the US varies depending on NCHS or WHO definitions.

INTRODUCTION: We compared the ranking of Alzheimer's disease and related dementia (ADRD) among the leading causes of death (LCODs) between those according to the National Center for Health Statistics (NCHS) and the World Health Organization (WHO) lists by sex. METHOD: The number of deaths in each LCOD category was obtained from CDC WONDER. RESULTS: According to the WHO list, ADRD was the second LCOD from 2005 to 2013, the first from 2014 to 2020, and the third in 2021, respectively, for women and was the second in 2018 and 2019, the third in 2020, and the fourth in 2021, respectively, for men. According to the NCHS list, Alzheimer's disease was the fourth in 2019 and 2020 for women and was the seventh from 2016 to 2019 for men. DISCUSSION: The ranking of ADRD among the LCODs according to the WHO list was higher than those according to the NCHS list.

Glucocorticoid receptor (NR3C1) genetic polymorphisms and the outcomes of sudden sensorineural hearing loss.

BACKGROUND: The glucocorticoid receptor gene (NR3C1) encodes the receptor to which cortisol and other glucocorticoids bind. Steroids in either oral, intratympanic, or intravascular forms are the treatment of choice for sudden sensorineural hearing loss (SSNHL), but the outcome varies. The outcomes of SSNHL have been investigated for related factors, including age, initial hearing loss severity and pattern, vertigo, genetic variations, and the time between onset and treatment. The objective of the present study was to analyze the association of genetic polymorphisms of NR3C1 with the outcomes of SSNHL. MATERIALS AND METHODS: We conducted a comparison study of 93 cases with a poor outcome (control) and 100 cases with a good outcome (case) in SSNHL patients. Six single nucleotide polymorphisms (SNPs) were selected. The genotypes were determined using TaqMan technology. RESULTS: The heterozygous AT genotype of rs17100289 was associated with a poor outcome in comparison with the major homozygous AA genotype after adjustments for age and sex (OR = 0.50; 95% CI 0.26-0.95; P = 0.035) in SSNHL patients. The CT genotype of rs4912912 was also associated with a poor outcome compared with the major homozygous TT genotype after the adjustments (OR = 0.47; 95% CI 0.24-0.92; P = 0.026). CONCLUSION: These results suggest that NR3C1 genetic polymorphisms may influence the outcomes of SSNHL.

Abortion and Female Cancer Risks among Women Aged 20 to 45 Years: A 10-Year Longitudinal Population-Based Cohort Study in Taiwan.

BACKGROUND: Female cancers, including breast, cervical, uterine, and ovarian cancer, remain among the ten most common cancers among women worldwide, but the relationship between female cancers and abortion from previous studies is inconsistent. This study aimed to investigate risks of incident female cancers among women aged 20 to 45 years who underwent abortion in Taiwan compared with those who did not. METHOD: A longitudinal observational cohort study was conducted using three nationwide population-based databases in Taiwan, focusing on 20- to 45-year-old women, with 10 years of follow-up. Matched cohorts were identified with propensity score 1-to-3 matching between 269,050 women who underwent abortion and 807,150 who did not. Multivariable Cox proportional hazard modeling was used for analysis after adjusting for covariates including age, average monthly payroll, fertility, diabetes mellitus, polycystic ovarian syndrome, endometrial hyperplasia, endometriosis, hormone-related drugs, and Charlson comorbidity index. RESULTS: We found lower risk of uterine cancer (hazard ratio [HR]: 0.77, 95% CI: 0.70-0.85) and ovarian cancer (HR: 0.81, 95% CI: 0.75-0.88), but no significant difference in risk of breast cancer or cervical cancer, among matched abortion compared with non-abortion cohorts. Regarding subgroup analysis, cervical cancer risk was higher for parous women who underwent abortion, and uterine cancer risk was lower for nulliparous women who underwent abortion compared with non-abortion groups. CONCLUSIONS: Abortion was related to lower uterine and ovarian cancer risk but was not associated with risks of incident breast cancer or cervical cancer. Longer follow-up may be necessary to observe risks of female cancers at older ages.

Facial canal dehiscence, dural exposure, and labyrinthine fistula in middle ear cholesteatoma and mastoiditis.

PURPOSE: To analyze the prevalence and associations of facial canal dehiscence (FCD), dural exposure, and labyrinthine fistula in chronic otitis media (COM) with and without cholesteatoma. METHODS: This was a retrospective study performed in an academic medical center. Patients who received tympanoplasty with mastoidectomy for COM with and without cholesteatoma were included. The prevalence of FCD, dural exposure, and labyrinthine fistula in COM with and without cholesteatoma (mastoiditis) and their relationships were analyzed. RESULTS: A total of 189 patients, including 107 (56.6%) females and 82 (43.4%) males, with 191 ears were included. There were 149 cases (78.0%) of cholesteatoma and 42 patients (22.0%) with mastoiditis. FCD was noted in 27.5% of patients with cholesteatoma and 9.5% of patients with mastoiditis. Dural exposure was found in 21 patients (14.1%) with cholesteatoma and 4 patients (9.5%) with mastoiditis. Eleven patients (7.4%) with cholesteatoma and 1 patient (2.4%) with mastoiditis had labyrinthine fistula. Patients with a labyrinthine fistula had nearly a fivefold greater chance (OR = 4.924, 95% CI = 1.355-17.896, p = 0.015) of having FCD than those without a fistula. There was a positive correlation between dural exposure and labyrinthine fistula (P = 0.011, Fisher's exact test). CONCLUSION: FCD, dural exposure, and labyrinthine fistula are common complications in COM. These complications are more frequently observed in patients with cholesteatoma than in patients with mastoiditis. Surgeons should pay more attention to the treatment of COM.

Changes in the rankings of leading causes of death in Japan, Korea, and Taiwan from 1998 to 2018: a comparison of three ranking lists.

BACKGROUND: The ranking lists used by most countries for leading causes of death (CODs) comprise broad category such as cancer, heart disease, and accidents. To provide more specific information, the World Health Organization (WHO) and the Institute of Health Metrics and Evaluation (IHME) proposed lists that splitting broad categories into specific categories. We examined the changes in rankings of leading CODs according to different lists in Japan, Korea, and Taiwan from 1998 to 2018. METHODS: We obtained the number of deaths for three countries from the WHO mortality database for 1998, 2008, and 2018. Age-standardized death rates were calculated for rankings 10 leading CODs using WHO 2000 age structure as standard. RESULTS: The first leading COD was cancer in Japan, Korea, and Taiwan from 1998 to 2018 based on government list; nevertheless, became stroke based on WHO list, and was stroke and ischemic heart disease based on IHME list. In the WHO and IHME lists, cancer is categorized based on cancer site. The number of cancer sites included in the 10 leading CODs in 2018 was 4, 4, and 3 in Japan, Korea, and Taiwan, respectively according to the WHO list and was 4, 4, and 2, respectively according to IHME list. The only difference was the rank of liver cancer in Taiwan, which was 6th according to WHO list and was 18th according to IHME list. The ranking and number of deaths for some CODs differed greatly between the WHO and IHME lists due to the reallocation of "garbage codes" into relevant specific COD in IHME list. CONCLUSIONS: Through the use of WHO and the IHME lists, the relative importance of several specific and avoidable causes could be revealed in 10 leading CODs, which could not be discerned if the government lists were used. The information is more relevant for health policy decision making.

Impacts of using different standard populations in calculating age-standardised death rates when age-specific death rates in the populations being compared do not have a consistent relationship: a cross-sectional population-based observational study on US state HIV death rates.

OBJECTIVE: To examine if the rankings of state HIV age-standardised death rates (SDRs) would be different if different standard populations (SPs) were used when age-specific death rates (ASDRs) in states being compared do not have a consistent relationship. DESIGN: A cross-sectional population-based observational study. SETTING: 36 states in the USA. PARTICIPANTS: Residents living in the 36 states. MAIN OUTCOME MEASURES: HIV SDR by state using two SPs, namely US2000 and US2020. RESULTS: US HIV ASDR by state did not have consistent relationships. Of 36 states analysed, the HIV death rates of people aged 55-64 years were higher than people aged 45-54 years in 20 states; on the contrary, the HIV death rates of people aged 55-64 years were lower than people aged 45-54 years in 16 states. No change in ranking in 19 states and change in ranking in 17 states. Of the 17 states whose rankings changed, the rankings of 9 states calculated using US2000 were higher (lower SDR) than those calculated using US2020; in 8 states, the rankings were lower (higher SDR). The states with the greatest changes in rankings between US2000 and US2020 were Kentucky (12th and 9th, respectively) and Massachusetts (8th and 11th, respectively). CONCLUSIONS: Calculating SDR using elder SP (US2020) would disproportionately increase the SDR in states with peak HIV death rate in older adults than those used younger SP (US2000).

Which ICD-9 codes were assigned for malignant mesothelioma in the mortality data in the United States before the ICD-10 was introduced?

BACKGROUND: Malignant mesothelioma (MM) is rare and fatal; survival in most cases is only about one year. Mortality rate is, therefore, a good proxy measure of incidence rate. However, the specific International Classification of Diseases (ICD) code for MM was not available until the Tenth Revision ICD (ICD-10). Little is known on which Ninth Revision ICD (ICD-9) codes were assigned for MM in the ICD-9 era. METHODS: We used a 1996 double-coded mortality file compiled by the National Center for Health Statistics to calculate the detection rate (DR) and confirmation rate (CR) of selected ICD-9 codes. RESULTS: Of 2386 decedents whose underlying cause of death was MM (ICD-10 code C45), the DR (deaths) of corresponding ICD-9 code was 57% (1365) for code 199 "malignant neoplasm without specification of site;" 19% (448) for code 162.9 "malignant neoplasm of trachea, bronchus, and lung, unspecified;" 13% (310) for code 163 "malignant neoplasm of pleura;" and 11% (271) for other codes. The CR (deaths) for the aforementioned three ICD-9 codes were 4.0% (1365/33,942), 0.3% (448/150,342), and 70.8% (310/438), respectively. CONCLUSIONS: The three ICD-9 codes (199, 162.9, and 163) were the most commonly used codes for MM and composed nine-tenths of all MM deaths in the years before the ICD-10 was introduced. Using only ICD-9 code 163, the code most often used as the surrogate measure of MM in mortality studies in the ICD-9 era, capture may have been only 13% of all MM deaths in the US, and the estimated number of MM deaths missed in 1996 would be 2086.

The association of genetic polymorphisms in interleukin-1 receptors type 1 and type 2 with sudden sensorineural hearing loss in a Taiwanese population: a case control study.

BACKGROUND: Sudden sensorineural hearing loss (SSNHL) is a disease with an unknown etiology; damage to the auditory nerve from inflammation due to viral infection or vascular incidents has been implicated. According to several studies, cytokines, including interleukins, are associated with SSNHL in terms of serum expression and genetic polymorphisms. Interleukin-1 (IL-1) plays a key role in inflammation and may be associated with SSNHL. This study analyzed the association of single nucleotide polymorphisms (SNPs) of IL-1 receptor (IL-1R) genes with SSNHL in Taiwan. METHODS: We conducted a case-control study involving 401 patients with SSNHL and 730 healthy controls. Four SNPs (IL-1R type 1 gene [IL1R1] [rs3917225 and rs2234650] and IL-1R type 2 gene [IL1R2] [rs4141134 and rs2071008]) were selected. The genotypes were determined using the TaqMan assay. The Hardy-Weinberg equilibrium (HWE) was tested for each SNP, and genetic effects were evaluated. RESULTS: The TT genotype of rs2234650 had an adjusted odds ratio (OR) of 2.988 (95% confidence interval [95% CI] 1.27-6.82) (P = 0.012) compared with the CC genotype in patients with SSNHL. The SNP rs2234650 was associated with SSNHL in the recessive model (TT vs. CC + CT, P = 0.0206, OR = 2.681). The CT genotype of rs4141134 had an adjusted OR of 3.860 (95% CI 2.01-7.44; P < 0.0001) compared with the TT genotype, in patients with SSNHL. The SNP rs4141134 was associated with SSNHL under the dominant model (CC + CT vs. TT, P < 0.0001, OR = 4.087). CONCLUSION: These findings suggest that IL1R1 and IL1R2 gene polymorphisms may contribute to an increased risk of SSNHL in Taiwan.

Association of sudden sensorineural hearing loss with dementia: a nationwide cohort study.

BACKGROUND: Impaired cochlear blood perfusion and microvascular damage can cause sudden sensorineural hearing loss (SSHL), which is a potential risk factor for dementia. This study explored the association between SSHL and dementia. METHODS: This retrospective cohort study used a random sample of 1000,000 individuals from Taiwan's National Health Insurance Research Database. We identified 3725 patients newly diagnosed with SSHL between January 1, 2000, and December 31, 2009, and propensity score matching according to age, sex, index year, comorbidities, and medications was used to select the comparison group of 11,175 patients without SSHL. Participants were stratified by age (<65 and ≧65 years) and sex for the subgroup analyses. The outcome of interest was all cause dementia (ICD-9-CM codes 290.0, 290.4, 294.1, 331.0). Both groups were followed up until December 31, 2010, for diagnoses of dementia. Cox regression models were used to estimate the hazard ratio (HR) of dementia. RESULTS: During the average 5-year follow-up period, the incidence rate of dementia in the SSHL cohort was 6.5 per 1000 person-years compared with 5.09 per 10,000 person-years in the comparison group. After adjustment for potential confounders, patients with SSHL were 1.39 times more likely to develop dementia than those without SSHL (95% confidence interval = 1.13-1.71). When stratified by patients' age and sex, the incidence of dementia was 1.34- and 1.64-fold higher in patients with SSHL aged ≥65 years (P = .013) and in women (P = .001), respectively, compared with the comparison group. Women with SSHL who were < 65 years old had the highest risk (2.14, 95% CI = 1.17-4.11, P = .022). In addition, a log-rank test revealed that patients with SSHL had significantly higher cumulative incidence of dementia than those without SSHL (P = .002). CONCLUSIONS: Patients with SSHL, especially women aged < 65 years, were associated with higher risk of dementia than those without SSHL. Thus, clinicians managing patients with SSHL should be aware of the increased risk of dementia.

How Malignant Mesothelioma Was Coded in Mortality Data in Taiwan During Years When the Specific ICD Code Was Not Available?

PURPOSE: Malignant mesothelioma (MM) is associated with past exposure to asbestos and the latency period ranged from 20 to 40 years. Asbestos consumption reached a peak in the 1980s in Taiwan, and the MM mortality is expected to increase since 2000s. However, no specific code for MM was available before the International Classification of Disease, Tenth Revision (ICD-10), which was launched in 2008 in Taiwan. We examined how MM was coded in mortality data in Taiwan during the years when the ICD, Ninth Revision (ICD-9) was used. PATIENTS AND METHODS: Double-coded mortality data (each death coded according to both ICD-10 and ICD-9 codes) for the period 2002-2008 were obtained for analysis. Detection rates (similar to sensitivity) and confirmation rates (similar to positive predictive value) for various potential proxy ICD-9 codes for MM were calculated. RESULTS: For 113 deaths, for which the underlying cause of death was ICD-10 code C45 (MM), 14 corresponding ICD-9 codes were used. Four ICD-9 codes constituted 77% (87/113) of all MM deaths. The detection rate for code 199 (malignant neoplasm [MN] without specification of site) was 37% (42/113), that for code 163 (MN of pleura) was 18% (20/113), that for code 162 (MN of trachea, bronchus, and lung) was 12% (14/113), and that for code 173 (other MN of skin) was 10% (11/113). The confirmation rates for codes 199, 163, 162, and 173 were 0.9% (42/4759), 14.3% (20/140), 0.03% (14/51,778), and 1.5% (11/717), respectively. CONCLUSION: ICD-9 codes 199, 163, 162, and 173 were most commonly used for MM deaths in Taiwan during the years before the ICD-10 introduction. However, when we used only ICD-9 code 163, which was most commonly used as a surrogate measure of MM in mortality studies during the ICD-9 era, we could detect only one-fifth of MM deaths in Taiwan.

Urban-Rural Disparities in the Incidence of Diabetes-Related Complications in Taiwan: A Propensity Score Matching Analysis.

Although a disparity has been noted in the prevalence and outcome of chronic disease between rural and urban areas, studies about diabetes-related complications are lacking. The purpose of this study was to examine the association between urbanization and occurrence of diabetes-related complications using Taiwan's nationwide diabetic mellitus database. In total, 380,474 patients with newly diagnosed type 2 diabetes between 2000 and 2008 were included and followed up until 2013 or death; after propensity score matching, 31,310 pairs were included for analysis. Occurrences of seven diabetes-related complications of interest were identified. Cox proportional hazards model was used to determine the time-to-event hazard ratio (HR) among urban, suburban and rural groups. We found that the HRs of all cardiovascular events during the five-year follow-up was 1.04 times (95% confidence interval (CI) 1.00-1.07) and 1.15 times (95% CI 1.12-1.19) higher in suburban and rural areas than in urban areas. Patients in suburban and rural areas had a greater likelihood of congestive heart failure, stroke, and end-stage renal disease than those in urban areas. Moreover, patients in rural areas had a higher likelihood of ischemic heart disease, blindness, and ulcer than those in urban areas. Our empirical findings provide evidence for potential urban-rural disparities in diabetes-related complications in Taiwan.

Glutathione peroxidase 3 gene polymorphisms and the risk of sudden sensorineural hearing loss.

The glutathione peroxidase 3 gene (GPX3) is reported to be a risk factor for arterial ischaemic stroke and cerebral venous thrombosis. GPX3 may be one of the aetiologies of sudden sensorineural hearing loss (SSNHL), which might be attributed to the genetic effect of GPX3 by influence reactive oxygen species (ROS). Unbalanced ROS have been associated with susceptibility to SSNHL. Therefore, we conducted a case-control study with 416 SSNHL cases and 255 controls. Five single nucleotide polymorphisms (SNPs) were selected. The genotypes were determined using TaqMan genotyping assays. Each SNP was tested using the Hardy-Weinberg equilibrium (HWE), and the genetic effects were evaluated using three inheritance models. All five SNPs were in HWE. As the result, the AG genotype of rs3805435 had an adjusted odds ratio (OR) of 0.54 (95% confidence interval = 0.37-0.79, p = 0.001) compared with the AA genotype in the SSNHL cases. The GG and AG genotypes of the SNP rs3805435 were associated with SSNHL under the dominant model (p = 0.002, OR = 0.58). In conclusion, these results suggest that GPX3 polymorphisms influence susceptibility to SSNHL in southern Taiwan.

Cilostazol Use Is Associated with Reduced Risk of Dementia: A Nationwide Cohort Study.

Whether antiplatelet agents have a preventive effect on cognitive function remains unknown. We examined the potential association between the use of cilostazol, an antiplatelet agent and cyclic adenosine monophosphate phosphodiesterase 3 inhibitor, and the risk of dementia in an Asian population. Patients initiating cilostazol therapy between 1 January 2004 and 31 December 2009 without a prior history of dementia were identified from Taiwan's National Health Insurance database. Participants were stratified by age, sex, comorbidities, and comedication. The outcome of interest was all-cause dementia (ICD-9-CM codes 290.0, 290.4, 294.1, 331.0). Cox regression models were used to estimate the hazard ratio (HR) of dementia. The cumulative cilostazol dosage was stratified by quartile of defined daily doses using no cilostazol use as a reference. A total of 9148 participants 40 years of age or older and free of dementia at baseline were analyzed. Patients using cilostazol (n = 2287) had a significantly decreased risk of incident dementia compared with patients not using the drug [n = 6861; adjusted HR (aHR) 0.75; 95% confidence interval (CI) 0.61-0.92]. Notably, cilostazol use was found to have a dose-dependent association with reduced rate of dementia emergence (p for trend = 0.001). Subgroup analysis identified a decline of dementia in cilostazol users with diagnosed ischemic heart disease (aHR 0.44, 95% CI 0.24-0.83) and cerebral vascular disease (aHR 0.34, 95% CI 0.21-0.54). These observations suggest that cilostazol use may reduce the risk to develop dementia, and a high cumulative dose further decreases the risk of dementia. These findings should be examined further in randomized clinical trials.

Cilostazol as an add-on therapy for patients with Alzheimer's disease in Taiwan: a case control study.

BACKGROUND: Combination therapy using acetylcholinesterase inhibitors (AChEIs) and cilostazol is of unknown efficacy for patients with Alzheimer's disease (AD). METHODS: We explored the therapeutic responses by using a case-control study, which was conducted in Taiwan. We enrolled 30 participants with stable AD who were receiving cilostazol (50 mg) twice per day as an add-on therapy combined with AChEIs, and 30 participants as controls who were not receiving cilostazol as an add-on therapy. The therapeutic responses were measured using neuropsychological assessments and analyzed in relation to cilostazol use, apolipoprotein E genotype, and demographic characteristics. Mini-mental state examination (MMSE) and clinical dementia rating sum of boxes (CDR-SB) were administered at the outset of the study and 12 months later. Multiple logistic regression analysis was used to estimate the association between the therapeutic response and cilostazol use. RESULTS: For the therapeutic indicator of cognition, Cilostazol use (adjusted odds ratio (aOR) = 0.17, 95% confidence interval (CI) = 0.03-0.80), initial CDR-SB score (aOR = 2.06, 95% CI = 1.31-3.72), and initial MMSE score (aOR = 1.41, 95% CI = 1.11-1.90), but not age, sex, education, or ApoE ε4 status, were significantly associated with poor therapeutic outcomes. For the therapeutic indicator of global status, no significant association was observed between the covariates and poor therapeutic outcomes. CONCLUSIONS: Cilostazol may reduce the decline of cognitive function in stable AD patients when applied as an add-on therapy.