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In previous studies, researchers have used singing to treat respiratory function in patients with spinal cord injury. However, few studies have examined the way in which vocal training affects respiratory neural plasticity in patients with spinal cord injury. Vocal respiratory training (VRT) is a type of vocal muscle-related treatment that is often a component of music therapy (MT) and focuses on strengthening respiratory muscles and improving lung function. In this randomized controlled study, we analyzed the therapeutic effects of VRT on respiratory dysfunction at 3 months after cervical spinal cord injury. Of an initial group of 37 patients, 26 completed the music therapy intervention, which comprised five 30-minute sessions per week for 12 weeks. The intervention group (n = 13) received VRT training delivered by professional certified music therapists. The control group (n = 13) received respiratory physical therapy delivered by professional physical therapists. Compared with the control group, we observed a substantial increase in respiratory function in the intervention group after the 12-week intervention. Further, the nerve fiber bundles in the respiratory center in the medulla exhibited a trend towards increased diversification, with an increased number, path length, thickness, and density of nerve fiber bundles. These findings provide strong evidence for the effect of music therapeutic VRT on neural plasticity. This study was approved by the Ethics Committee of China Rehabilitation Research Center (approval No. 2020-013-1) on April 1, 2020, and was registered with the Chinese Clinical Trial Registry (registration No. ChiCTR2000037871) on September 2, 2020.

Background The human microbiome plays an important role in modulating the host metabolism and immune system. Connections and interactions have been found between the microbiome of the gut and oral pharynx in the context of SARS-CoV-2 and other viral infections; hence, to broaden our understanding of host-viral responses in general and to deepen our knowledge of COVID-19, we performed a large-scale, systematic evaluation of the effect of SARS-CoV-2 infection on human microbiota in patients with varying disease severity. Results We processed 521 samples from 203 COVID-19 patients with varying disease severity and 94 samples from 31 healthy donors, consisting of 213 pharyngeal swabs, 250 sputa, and 152 fecal samples, and obtained meta-transcriptomes as well as SARS-CoV-2 sequences from each sample. Detailed assessment of these samples revealed altered microbial composition and function in the upper respiratory tract (URT) and gut of COVID-19 patients, and these changes are significantly associated with disease severity. Moreover, URT and gut microbiota show different patterns of alteration, where gut microbiome seems to be more variable and in direct correlation with viral load; and microbial community in the upper respiratory tract renders a high risk of antibiotic resistance. Longitudinally, the microbial composition remains relatively stable during the study period. Conclusions Our study has revealed different trends and the relative sensitivity of microbiome in different body sites to SARS-CoV-2 infection. Furthermore, while the use of antibiotics is often essential for the prevention and treatment of secondary infections, our results indicate a need to evaluate potential antibiotic resistance in the management of COVID-19 patients in the ongoing pandemic. Moreover, a longitudinal follow-up to monitor the restoration of the microbiome could enhance our understanding of the long-term effects of COVID-19.

IntroductionThe aim of this prospective study is to evaluate the effects of combining topical airway anaesthesia with intravenous induction on haemodynamic variables during the induction period in patients undergoing cardiac surgery.Methods and analysisThis randomised, double-blind, controlled, parallel-group, superiority study from 1 March 2021 to 31 December 2021 will include 96 participants scheduled for cardiac surgery. Participants will be screened into three blocks (ASA II, ASA III, ASA IV) according to the American Society of Anesthesiologists (ASA) grade and then randomly allocated into two groups within the block in a 1:1 ratio. Concealment of allocation will be maintained using opaque, sealed envelopes generated by a nurse according to a computer-generated randomisation schedule. In addition to general intravenous anaesthetics, participants will receive supraglottic and subglottic topical anaesthesia. Changes in arterial blood pressure and heart rate in both groups will be recorded by an independent investigator at the start of anaesthesia induction until the skin incision. If vasopressors are used during this period, the frequency, dosage and types of vasopressors will be recorded. The incidence and severity of participants’ postoperative hoarseness and sore throat will also be assessed.Ethics and disseminationThis study was approved by the Ethics Committee of Qianfoshan Hospital of Shandong Province (registration number: YXLL-KY-2021(003)). The results will be disseminated through a peer-reviewed publication and in conferences or congresses.Trial registration numberNCT04744480.

Key Points: Question: Can the traditional Chinese version of the hearing handicap inventory for elderly screening (HHIE-S) checklist screen for age-related hearing loss (ARHL) in elderly individuals? Findings: In this cross-sectional study of 1696 Taiwanese patients who underwent annual government-funded geriatric health checkups, the Chinese version of the HHIE-S had a sensitivity of 76.9% and a specificity of 79.8% with a cutoff score greater than 6 for identifying patients with disabled hearing loss (defined as a PTA > 40 dB). Meaning: The traditional Chinese version of the HHIE-S is an effective test to detect ARHL and can improve the feasibility of large-scale hearing screening among elderly individuals. Purpose: The traditional Chinese version of the hearing handicap inventory for elderly screening (TC-HHIE-S) was translated from English and is intended for use with people whose native language is traditional Chinese, but its effectiveness and diagnostic performance are still unclear. The purpose of this study was to evaluate the validity and reliability of the traditional Chinese version of the HHIE-S for screening for age-related hearing loss (ARHL). Methods: A total of 1696 elderly people underwent the government’s annual geriatric medical examination at community hospitals. In this cross-sectional study, we recorded average conducted pure-tone averages (PTA) (0.5 kHz, 1 kHz, 2 kHz, 4 kHz), age, sex, and HHIE-S data. Receiver operating characteristic (ROC) curve analysis was used to identify the best critical point for detecting hearing impairment, and the validity of the structure was verified by the agreement between the TC-HHIE-S and PTA results. Results: The HHIE-S scores were correlated with the better-ear pure-tone threshold averages (PTAs) at 0.5–4 kHz (correlation coefficient r = 0.45). The internal consistency of the total HHIE-S score was excellent (Cronbach’s alpha = 0.901), and the test-retest reliability was also excellent (Spearman’s correlation coefficient = 0.60, intraclass correlation coefficient = 0.75). In detecting disabled hearing loss (i.e., PTA at 0.5–4 kHz > 40 dB), the HHIE-S cutoff score of > 6 had a sensitivity of 76.9% and a specificity of 79.8%. Conclusions: The traditional Chinese version of the HHIE-S is a valid, reliable, and efficient tool for large-scale screening for ARHL.

The study objective was to evaluate the association between cervical spondylosis (CS) and a subsequent diagnosis of obstructive sleep apnea (OSA) in light of the expected constricting impact of CS-associated cervical spine changes on the pharyngeal airway space, a key contributor to OSA.Data were retrieved from the Taiwan National Health Insurance Research Dataset. A total of 98,234 patients who newly received a diagnosis of OSA were identified. We identified four propensity score-matched controls per OSA patient (n = 392,936). Chi-square tests were used to compare cases and controls on sociodemographic characteristics, and multivariable logistic regression modelling to examine the association of OSA with prior CS.Of the 98,234 sampled patients, 18,070 (18.4%) patients had a prior CS diagnosis, significantly different among cases compared to controls, being 18.4% and12.1%, respectively, p 0.001. Logistic regression analysis showed an adjusted odds ratio (OR) of prior CS of 1.778 (95% confident interval (CI): 1.744-1.814) relative to controls. The adjusted odds of prior CS without myelopathy was 1.764 for cases relative to controls (95% CI: 1.727-1.801), and for prior CS with myelopathy (adjusted OR: 1.778, 95% CI: 1.721-1.837). Analysis stratified by age showed that in the 45-64- and64-year age groups, the adjusted ORs of CS were 1.803 (95% CI: 1.758-1.850) and 1.634 (95% CI: 1.568-1.703), respectively, for cases relative to controls.Our results suggest that OSA is associated with prior CS. The results call for professionals to be alert to the possibility of subsequent development of OSA among patients with CS.

Chronic human immunodeficiency virus (HIV) infection not only causes a gradual loss of CD4+ T cells but also leads to a disturbance of the T cell receptor (TCR) repertoire. In people living with HIV (PLWH), monitoring TCR repertoire is challenged by the inconsistency of complementarity determining region 3 (CDR3) and limited cell numbers in clinical samples. Thus, a quantitative method is necessary for monitoring the TCR repertoire in PLWH. We characterized the TCR V-J pairing profile of naïve and memory CD4+ T cells in healthy donors, HIV-infected antiretroviral therapy (ART)-naïve patients and long-term (over 5 years) ART-experienced patients by performing TCR sequencing. We developed a V-J index with 18 parameters which were subdivided into five categories (expression coverage, cumulative percentage of the top tenth percentile, diversity, intra-individual similarity and inter-individual similarity). In ART-naïve patients, 14 of the 18 parameters were significantly altered. Long-term ART recovered ten parameters. The four unrecovered parameters were related to inter-individual similarity. Therefore, these findings indicate that long-term ART could only partially recover TCR V-J pairs and introduce newly impacted V-J pairs. Moreover, these results provide new insights into the V-J pairing of the TCR and into the disturbance of TCR repertoire in HIV infection. Electronic Supplementary Material Supplementary material is available for this article at 10.1007/s11427-020-1718-2 and is accessible for authorized users.

Background Tinnitus due to hyperactivity across neuronal ensembles along the auditory pathway is reported. We hypothesized that trigeminal neuralgia patients may subsequently suffer from tinnitus. Using nationwide, population-based data and a retrospective cohort study design, we investigated the risk of tinnitus within 1 year following trigeminal neuralgia. Methods We used the Taiwan National Health Insurance Research Dataset, a claims database, to identify all patients diagnosed with trigeminal neuralgia from January 2001 to December 2014, 12,587 patients. From the remaining patients, we identified 12,587 comparison patients without trigeminal neuralgia by propensity score matching, using sex, age, monthly income, geographic region, residential urbanization level, and tinnitus-relevant comorbidities (hyperlipidemia, diabetes, coronary heart disease, hypertension, cervical spondylosis, temporomandibular joint disorders and injury to head and neck and index year). All study patients (n = 25,174) were tracked for a one-year period to identify those with a subsequent diagnosis of tinnitus over 1-year follow-up. Results Among total 25,174 sample patients, the incidence of tinnitus was 18.21 per 100 person-years (95% CI = 17.66 ~ 18.77), the rate being 23.57 (95% CI = 22.68 ~ 24.49) among patients with trigeminal neuralgia and 13.17 (95% CI = 12.53 ~ 13.84) among comparison patients. Furthermore, the adjusted Cox proportional hazard ratio for tinnitus in the trigeminal neuralgia group was 1.68 (95% CI = 1.58 ~ 1.80) relative to the comparison cohort. Conclusions We found a significantly increased risk of tinnitus within 1 year of trigeminal neuralgia diagnosis compared to those without the diagnosis. Further studies in other countries and ethnicities are needed to explore the relationship between trigeminal neuralgia and subsequent tinnitus.

BACKGROUND This study aimed to evaluate the association between pioglitazone use and the occurrence of head and neck cancer. METHODS Data for this case-control study were retrieved from the Taiwan National Health Insurance Research Database. A total of 21 464 diabetic patients newly diagnosed with head and neck cancers were identified. We used propensity score matching to select 64 392 comparison patients (3:1 ratio). Multiple logistic regression modeling was used to examine the association of head and neck cancer with pioglitazone use in the 5 years preceding the cancer diagnosis. RESULTS Bivariate analysis showed a significant difference in the prevalence of prior using pioglitazone between cases and controls (19.3% vs 18.5%, P

Guided bone regeneration (GBR) is an effective alveolar ridge reconstruction technique used before or at implant placement. The combination of various barrier membranes and bone substitutes has been employed. This study aimed to perform a preliminarily evaluation of the safety and performance of a new nonabsorbable bi-layered porous polyethylene (PPE) membrane, in combination with a freeze-dried cortical bone allograft in posterior mandibular ridge augmentation. Fifteen adults who had combined posterior mandibular defects were included for ridge augmentation via GBR using PPE membrane and allograft before implant placement. The keratinized mucosa width (KW), ridge width (RW), ridge height (RH), distance from measurement matrix to bone (DMB), and horizontal alveolar width at 14.0 mm apical to the occlusal plane (HAW) were clinically measured at 15 intended implant sites before and after the augmentation. Fifteen biopsy specimens were harvested at the implant sites for histological analysis. All the subjects completed the whole study. The KW and RH showed minor gains by 0.2 ± 1.4 mm and 0.9 ± 2.3 mm respectively; however, no statistically significant differences were found between, before, and after the augmentation (P > 0.05). In contrast, the RW and HAW significantly increased by 4.8 ± 1.6 mm and 2.3 ± 1.7 mm, respectively, (P ≤ 0.001), while DMB significantly decreased by 1.0 ± 0.8 mm after treatment (P < 0.001). Histological analysis revealed that allograft underwent active bone remodeling. The PPE membrane was adequately safe and efficient to use with allograft in GBR for the reconstruction of combined ridge defects. Although some complications were observed, these were manageable and subsequently lead to successful implant placement for all the subjects. However, further randomized controlled trials are still needed to confirm these findings.

Background & AimsTenofovir disoproxil fumarate (TDF) imposes a high genetic barrier to drug resistance and potently inhibits replication of multidrug-resistant hepatitis B virus (MDR HBV) and few clinical cases with confirmed TDF-resistance have been reported to date. We reported a quadruple mutant which showed moderate resistant to TDF.Methods and resultsViral rebound was reported in a patient with chronic hepatitis B who underwent TDF monotherapy and harbored a quadruple mutant consisting of classic ETV-resistance mutations (rtL180M/T184L/M204V) together with an rtA200V mutation in the reverse transcriptase gene. Sequencing analysis revealed that this quadruple mutant emerged as a major viral population. In vitro phenotyping demonstrated that the rtL180M/T184L/A200V/M204V mutant had moderate resistance to TDF treatment, with a 4.52-fold higher half maximal effective concentration than that of wild-type virus. Importantly, this patient with TDF resistance achieved virological suppression after TDF/ETV combination rescue therapy.ConclusionAn rtL180M/T184L/A200V/M204V mutant with moderate resistance to TDF monotherapy was selected during sequential NA treatment in a stepwise manner. ETV/TDF combination therapy effectively suppressed replication of this TDF resistant mutant. Our studies provide novel insights into the treatment of NA-naïve patients as well as patients with TDF resistance.

Purpose. To identify potential biomarkers and/or therapeutic targets for bladder cancer we characterized and analysed the composition of the urinary microbiota from bladder cancer and non-cancer patients. Methodology. In this study, we collected urine samples from 29 bladder cancer patients and 26 non-cancer patients. To avoid contamination and the impact of antibiotics, urine specimens were collected in a clean manner prior to antibiotic administration. Using the amplicon-based next-generation sequencing approach, the potential determinant bacteria were estimated in a between-group comparison. The results illustrated the differences in microbiota abundance among cancer and non-cancer patients and the overall number of cases carrying these bacteria. Results. We found that the urine samples contained a conserved microbiota with four phyla ( Firmicutes , Actinobacteria , Proteobacteria and Bacteroidetes ), which accounted for 94.4 % of bacteria in all cases. Comparing the microbiota between the bladder cancer and control group, five genera of bacteria ( Streptococcus , Bifidobacterium , Lactobacillus , Veillonella and Actinomyces ) existed in all samples, but with significant intergroup differences (P

Objectives: Most previous studies on poor immunological responders (PIRs) have been performed on one cohort at one time-point following highly active antiretroviral therapy (HAART). The aim of this study was to investigate whether there are different subtypes of PIR and whether a certain population might achieve better immune reconstitution following longer HAART. Methods: This study was designed as an ambispective cohort study, including a 4–5-year retrospective study and a 2-year prospective follow-up investigation. Thymic output, activated T cell and regulatory T cell (Treg) subset frequencies, expression levels of interferon-stimulated genes, and plasma concentrations of neopterin were determined at 4–5 years and 6–7 years following HAART initiation. Results: PIRs were subdivided into two populations after 4–5 years of HAART, according to the kinetics of T cell recovery. Type II PIRs exhibited a significantly lower percentage of naïve CD4+ T cells and CD31+ naïve CD4+ T cells compared with type I PIRs. After an additional 2 years of HAART treatment, type I PIRs showed a better outcome than type II PIRs. Furthermore, it was found that 2 years of additional HAART could persistently improve thymic output. Conclusions: The two PIR subgroups are different in terms of immune characteristics and the response to prolonged HAART. Keywords: Poor immunological responders, Subdivision, Thymic output, Long-term HAART

BackgroundThe global outbreak of coronavirus disease 2019 (COVID-19) has turned into a worldwide public health crisis and caused more than 100,000,000 severe cases. Progressive lymphopenia, especially in T cells, was a prominent clinical feature of severe COVID-19. Activated HLA-DR+CD38+ CD8+ T cells were enriched over a prolonged period from the lymphopenia patients who died from Ebola and influenza infection and in severe patients infected with SARS-CoV-2. However, the CD38+HLA-DR+ CD8+ T population was reported to play contradictory roles in SARS-CoV-2 infection.MethodsA total of 42 COVID-19 patients, including 32 mild or moderate and 10 severe or critical cases, who received care at Beijing Ditan Hospital were recruited into this retrospective study. Blood samples were first collected within 3 days of the hospital admission and once every 3–7 days during hospitalization. The longitudinal flow cytometric data were examined during hospitalization. Moreover, we evaluated serum levels of 45 cytokines/chemokines/growth factors and 14 soluble checkpoints using Luminex multiplex assay longitudinally.ResultsWe revealed that the HLA-DR+CD38+ CD8+ T population was heterogeneous, and could be divided into two subsets with distinct characteristics: HLA-DR+CD38dim and HLA-DR+CD38hi. We observed a persistent accumulation of HLA-DR+CD38hi CD8+ T cells in severe COVID-19 patients. These HLA-DR+CD38hi CD8+ T cells were in a state of overactivation and consequent dysregulation manifested by expression of multiple inhibitory and stimulatory checkpoints, higher apoptotic sensitivity, impaired killing potential, and more exhausted transcriptional regulation compared to HLA-DR+CD38dim CD8+ T cells. Moreover, the clinical and laboratory data supported that only HLA-DR+CD38hi CD8+ T cells were associated with systemic inflammation, tissue injury, and immune disorders of severe COVID-19 patients.ConclusionsOur findings indicated that HLA-DR+CD38hi CD8+ T cells were correlated with disease severity of COVID-19 rather than HLA-DR+CD38dim population.

Objective To investigate the safety of adenoidectomy and risk factors of re-adenoidectomy, and intend to provide evidence-based information to clinicians for further consideration. Methods and materials This study was based on data obtained from Taiwan’s National Health Insurance Research Database from the period 2002–2011. We utilized that data from the hospitalization group and collected information regarding those individuals who accepted adenoidectomy with or without tonsillectomy and post-adenoidectomy bleeding. Thereafter, we performed univariate and multi-variate analysis to explore the possible risk factors of re-adenoidectomy. Results A total of 5435 individuals who accepted a first adenoidectomy with or without tonsillectomy were collected. After further tracing treatment of these individuals, 107 (1.97%) accepted the revision adenoidectomy until 2011. Post-op bleeding was approximately 0.28%. The revision rate associated with patient age showed the following: 0–4 years (0.61%), 4–12 years (2.06%) and 12–18 years (2.56%). The revision rate associated with surgeon age showed: 28–41 years (1.42%), 41–50 years (2.96%), 50–65 years (2.74%); the surgeons’ surgery volume showed low (4.34%), medium (0.71%), and higher (1.02%). There are 4 diseases (otitis media with effusion, sinusitis, chronic pharyngitis, and sleep disorder) that showed a significant relationship with the revision rate when subject to univariate and multivariate analysis. The revision rate incorporating hospital locations, volumes and levels revealed no significant difference with each other. Conclusions Adenoidectomy is a generally safe surgical procedure, with low complication and low revision rate. Our study indicated that the revision rate of adenoidectomy might be lower when performed by young visiting staff with medium to higher surgical volume in the medium to higher volume hospital. If patients had diseases such as otitis media with effusion, sinusitis, chronic pharyngitis, and sleep disorder, they would be subject to higher rate of re-adenoidectomy. Surgeons should be aware and sufficiently explain this information to the parents before surgery.

This study aimed to investigate the annual incidence of parapharyngeal and retropharyngeal abscess (PRPA) based on 10-year population-based data. Patients with PRPA were identified from the Taiwan Health Insurance Research Database, a database of all medical claims of a randomly selected, population-representative sample of over two million enrollees of the National Health Insurance system that covers over 99% of Taiwan&rsquo, s citizens. During 2007&ndash, 2016, 5779 patients received a diagnosis of PRPA. We calculated the population-wide incidence rates of PRPA by sex and age group (20&ndash, 44, 45&ndash, 64, and &gt, 64) as well as in-hospital mortality. The annual incidence rate of PRPA was 2.64 per 100,000 people. The gender-specific incidence rates per 100,000 people were 3.34 for males and 1.94 for females with a male:female gender ratio of 1.72. A slight increase in incidence rates among both genders over the study period was noted. Age-specific rates were lowest in the 20&ndash, 44 age group with a mean annual incidence of 2.00 per 100,000 people, and the highest rates were noted in the age groups of 45&ndash, 64 and &gt, 64 years with mean annual incidences of 3.21 and 3.20, respectively. We found that PRPA is common in Taiwan, males and older individuals are more susceptible to it, and incidence has increased in recent years.

Intrahost analysis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomic sequences identified 2 viral haplotypes comprised of 3 genetically linked mutations from the respiratory and intestinal tracts of a patient with coronavirus disease 2019. Spatiotemporal data suggest that this patient initially had dual infection of 2 SARS-CoV-2 variants, which subsequently redistributed into the 2 systems.

This population-based study aimed to study the association between tinnitus and cervical spondylosis.A case-control study.We retrieved data from the Taiwan Longitudinal Health Insurance Database. We identified 2465 patients with tinnitus (cases) and 7395 comparison patients by propensity score matching. Multivariable logistic regressions were conducted to estimate the odds (OR) of a diagnosis of cervical spondylosis preceding the tinnitus diagnosis relative to controls.We found that 1596 (16.19%) of 9860 sample patients had received a diagnosis of cervical spondylosis before the index date, significantly different between the tinnitus group and control group (17.20% vs. 15.85%,In conclusion, the study shows a positive association between cervical spondylosis and tinnitus. The findings call for greater awareness among physicians about a possible somatosensory component of cervical spine function which may contribute to tinnitus.

Objective : Gut microbiota has been proposed as a pivotal role in the progression of Spondyloarthritis (SpA), however diverse results remain to be synthesized. We performed a systematic review to collect evidence on the characteristic of the gut microbiota in patients with SpA, as compared to controls. Methods : We systematically searched MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials databases, through June 1, 2021 for studies that compared gut microbiota of cases with SpA versus healthy controls. Results : Of 3756 records identified, 28 studies from 23 articles were included in the analysis. Results of β-diversity showed SpA patients hold a significantly different microbial composition compared with controls. Several taxa-level differences of gut microbiota between SpA (and its subtypes) cases and controls were identified. Fourteen studies including only patients with ankylosing spondylitis (AS) reported increased amounts of Actinobacteria, Dialister, Streptococcus, and Clostridium bolteae, and decreased amounts of Bacteroidales and Parasutterella in AS cases versus controls in ≥ 3 studies. Dialister invisus was increased in axial-SpA cases versus controls in 3 studies. Bacteroides fragilis was increased in enthesitis-related arthritis (ERA) cases versus controls in 2 studies. For all SpA studies, Proteobacteria, Enterobacteriaceae, and Bacteroidaceae were increased, whereas Bacteroidetes, Bacteroidales, and Akkermansia were decreased in cases versus controls in ≥ 3 studies. Over 40% of the studies showed comparable data of both sex and age between cases and controls. Conclusion : The microbial characteristics of SpA summarized in the systematic review laid the groundwork for evidence-based microbial treatment. The microbial variance among subtypes of SpA remains to be explored. Further studies are needed to elucidate how the altered microbiota participate in the pathogenesis of SpA.

Singing, as a method of combining respiratory function exercise and vocal intonation therapy, provides a new direction for respiratory function exercise in patients with spinal cord injury. This randomized controlled trial investigated the effects of oral motor respiratory exercise and vocal intonation therapy on respiratory function and vocal quality in patients with spinal cord injury. Among 31 included patients with spinal cord injury, 18 completed the treatment. These 18 patients were randomly assigned to undergo music therapy (intervention group, 30 min/d, 5 times a week, for a total of 12 weeks; n = 9, 7 males and 2 females; 30.33 ± 11.74 years old) or normal respiratory training (control group, n = 9; 8 males and 1 female; 34.78 ± 11.13 years old). Both patient groups received routine treatment concurrently. Before and at 6 and 12 weeks after intervention, a standard respiratory function test, a voice test, the St. George's Respiratory Questionnaire, and a quality of life questionnaire were administered. The results showed that the inspiratory capacity, forced expiratory volume in 1 second, forced vital capacity, maximal mid-expiratory flow rate, sing-loud pressure level, and sustained note length were significantly increased in the intervention group compared with the control group. The St. George's Respiratory Questionnaire and quality of life results of patients in the intervention group were significantly superior to those in the control group. These findings suggest that oral motor respiratory exercise and vocal intonation therapy, as respiratory training methods in music therapy, are effective and valuable for improving respiratory dysfunction and vocal quality in patients with spinal cord injury. This study was approved by the Ethics Committee of China Rehabilitation Research Center (approval No. 2019-78-1) on May 27, 2019 and was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR1900026922) on October 26, 2019.

Higher rates of poor cognitive performance are known to prevail among persons with tinnitus in all age groups. However, no study has explored the association between tinnitus and early-onset dementia. We hypothesize that tinnitus may precede or occur concurrently with subclinical or early onset dementia in adults younger than 65 years of age. This case–control study used data from the Taiwan National Health Insurance Research Database, identifying 1308 patients with early-onset dementia (dementia diagnosed before 65 years of age) and 1308 matched controls. We used multivariable logistic regressions to estimate odds ratios (ORs) for prior tinnitus among patients with dementia versus controls. Among total 2616 sample participants, the prevalence of prior tinnitus was 18%, 21.5% among cases and 14.5% among controls (p

Congenital cytomegalovirus (cCMV) infection is the leading environmental cause of childhood hearing impairment. However, its significance remains largely undocumented in many regions of the world. The purpose of this study was to investigate the prevalence and clinical features of cCMV infection in East Asia. Neonates born at a municipal hospital in Taipei were prospectively recruited and underwent concurrent hearing and CMV screenings. Those who failed the hearing screening or screened positive for CMV were subjected to a focused audiological and/or virological surveillance. The characteristics of the newborns and their mothers were compared between the CMV-positive and CMV-negative groups. Of the 1,532 newborns who underwent concurrent hearing and CMV screenings, seven (0.46%) were positive for cCMV infection. All seven CMV-positive newborns were asymptomatic at birth, and none of them developed hearing or other symptoms during a follow-up period of 14.4±6.3 months. The mothers of the CMV-positive newborns demonstrated higher gravidity (2.4 ± 1.4 vs. 2.1 ± 1.2) and parity (2.0 ± 1.2 vs. 1.6 ± 0.7) than those in the CMV-negative group; however, the difference did not reach statistical significance. The prevalence of cCMV infection in Taipei newborns was 0.46%, which is slightly lower than that of other populations and that of a previous report in the Taiwanese population. The relatively low prevalence in this study might be attributed to the improved public health system and decreased fertility rate in Taiwan.

Objectives Human immunodeficiency virus (HIV) quasispecies diversity presents a large barrier to the eradication of HIV. The aim of this study was to investigate intrahost HIV quasispecies diversity and evolutionary patterns underpinning the mechanisms of viral pathogenesis during antiretroviral therapy (ART). Methods Forty-five participants with HIV-1 infection were enrolled in a follow-up cohort for >84 months in 2004, and received a lamivudine-based first-line ART regimen. Blood samples were collected every 6 months to measure viral load and CD4+ cell count. Ultra-deep sequencing and phylogenetic analysis were used to characterize the dynamics governing quasispecies diversity of HIV-1 circulating between plasma RNA and cellular DNA of participants with treatment failure (TF, n = 20) or virologic suppression (VS, n = 25). Results Analysis of the distribution of intrahost single-nucleotide variations (iSNVs) and their mutated allele frequencies revealed that approximately 65% of the quasispecies co-occurred in plasma HIV RNA and cellular DNA either before or after ART. The number and frequency of iSNVs are more representative of intrahost HIV diversity, and have better generalizability than phylogenetic inference by measurement of phylogenetic associations. Furthermore, drug-resistance-associated mutations (DRAMs) accumulated to high levels, dramatically increasing the DRAM-to-total-mutation ratio for TF patients. Linear regression analysis revealed that emergent mutations accumulated faster in TF patients compared with VS patients, at a rate of 0.02 mutations/day/kb. Conclusions Based on iSNV analysis, the results demonstrate the dynamics of intrahost HIV quasispecies diversity in patients on ART, and provide a novel insight into the persistence of HIV and development of DRAMs.

Background: The aim of this study was to compare the risk of developing sudden sensorineural hearing loss (SSHL) in patients with hypopharyngeal cancer with that in patients with nasopharyngeal carcinoma (NPC). Methods: A population-based, retrospective cohort study was performed using the Taiwan National Health Research Database databank. Patients selected for this study were diagnosed with hypopharyngeal cancer or NPC and treated with radiotherapy in the period from 2001 to 2004. Routine follow-up was conducted for 8 years (2004–2012), and the incidence of SSHL was calculated at the final follow-up. Results: There was no significant difference in the risk of developing SSHL between the hypopharyngeal cancer group and its control group (p = 1.000). In hypopharyngeal cancer and NPC groups, the rates of SSHL were 0.12% and 1.00%, respectively (p < 0.001). The cumulative hazard of SSHL during the follow-up period was significantly higher in the NPC group than in the control group (p < 0.001). Conclusion: Radiotherapy in patients with hypopharyngeal cancer did not increase the risk of developing SSHL, but postirradiation NPC was significantly associated with an increased incidence of SSHL.

This study aimed to evaluate the prevalence of peripheral vestibular disorders in an Asian population of predominantly Han Chinese ethnicity.Cross-sectional study.Patients with a peripheral vertigo disorder were identified from the Taiwan Health Insurance Research Database, a database of all medical claims of a randomly selected, population-representative sample of 2 million enrollees of Taiwan's National Health Insurance system covering over 99% of Taiwan's citizens. In 2016, 59,986 patients received a diagnosis of peripheral vestibular disorders in Taiwan. We calculated the population-wide prevalence rates of peripheral vestibular disorders in 2016 by sex and age group (20 to 24, 25 to 29, 30 to 34, 35 to 39, 40 to 44, 45 to 49, 50 to 54, 55 to 59, 60 to 64, 65 to 69, and ≥ 70 years) stratified into five urbanization levels.The prevalence rate of peripheral vestibular disorders was 2,833.4 per 100,000 population during the year. Prevalence of Meniere's disease was 70.4 per 100,000, benign paroxysmal positional vertigo, 446.4, vestibular neuritis 307.2, and other or unspecified peripheral vestibular dizziness, 2,009.5 per 100,000. Prevalence rates steadily increased with age for every type of peripheral vestibular disorder, and were higher among females compared to males. The female-to-male gender ratios were 1.84, 1.89, and 1.93 for Meniere's disease, vestibular neuritis, and other peripheral vestibular dizziness, respectively. Counties with the lowest urbanization level had the highest prevalence rates of all types of peripheral vestibular disorders except vestibular neuritis.Results showed that peripheral vestibular disorders are common in Taiwan, increase with age, are predominantly female, and show higher prevalence in rural areas.2b Laryngoscope, 131:639-643, 2021.

Objective: Despite studies reporting a possible association between malignant otitis externa (MOE) and diabetes, there are no large-scale population-based empirical studies. This nationwide, population-based case-control study explored the association of MOE occurrence with previously diagnosed diabetes. Methods: Data were retrieved from Taiwan’s National Health Insurance Research Database, 753 patients with MOE (cases) and 2 259 propensity score-matched patients without MOE (controls). Multiple logistic regressions were conducted to examine the association of MOE with previously diagnosed diabetes. Results: In total, 728 (24.2%) out of 3 012 sample patients had diabetes prior to the index date. Chi-square test revealed a significant difference in diabetes prevalence among cases and controls (54.8% vs 13.9%, p Conclusions: This study found an association between MOE and diabetes. One clinical practice implication of our study is that when a patient with diabetes complains of otalgia or otorrhea, and physical examination shows swelling of the ear canal or granulation growth, physicians should consider the possibility of MOE.

Neutropenia and impaired functions were common manifestation in antiretroviral therapy (ART) in both naïve and experienced PLWHA. Granulopoiesis can be divided into two phases: lineage determination and committed granulopoiesis. However, stage-specific impairment of granulopoiesis in PLWHA with neutropenia remains unclear. A total of 48 ART-naïve and 49 ART-experienced PLWHA from 2016 to 2018 were recruited and divided into non-, mild-, and moderate-to-severe-neutropenia groups according to their neutrophil counts. The bone marrow aspirates and peripheral blood were collected and analyzed by multicolor flow cytometry for granulocyte subsets, hematopoietic stem/progenitor cells (HSPC), apoptosis, and emigration and retention of different subsets. Compared with healthy donors, the percentages of circulating segmented neutrophils were significantly decreased along with an increase of immature neutrophils in both groups. ART-naïve patients with moderate to severe neutropenia exhibited decreased proportion and accelerated apoptosis of relative mature segmented neutrophils. In contrast, ART-experienced patients with neutropenia displayed decreased proportion of granulocyte macrophage progenitors, indicating a defect at a stage of lineage determination. Meanwhile, ART-experienced patients with neutropenia also the expression of CXCR4 segmented neutrophils, suggesting an increased retention of segmented neutrophils inn the bone marrow. ART-naïve patients with neutropenia is caused by increased apoptosis of relatively differentiated neutrophils at committed granulopoiesis, whereas impaired lineage determination and enhanced retention of segmented neutrophils contribute to in ART-experienced patients.

Rabbit hemorrhagic disease virus (RHDV) is responsible for rabbit hemorrhagic disease (RHD), which is an acute, lethal and highly contagious disease in both wild and domestic rabbits. Although current vaccines are highly effective for controlling RHD, they are derived from infected rabbit livers and their use is thus associated with safety and animal-welfare concerns. In this study, we generated a recombinant lentogenic canine adenovirus type 2 (CAV2) vector expressing the RHDV vp60 gene, named rCAV2-VP60. rCAV2-VP60 expressed VP60 protein in Madin-Darby canine kidney cells as demonstrated by western blot and immunofluorescence assay. Polymerase chain reaction confirmed that the vp60 gene was successfully inserted into rCAV2-VP60 and was still detectable after 20 passages, indicating its stable genetic character. We evaluated the feasibility of rCAV2-VP60 as a live-virus-vectored RHD vaccine in rabbits. rCAV2-VP60 significantly induced specific antibodies to RHDV and provided effective protection against RHDV lethal challenge. These results suggest that rCAV2 expressing RHDV VP60 could be a safe and efficient candidate vaccine against RHDV in rabbits.

Objectives: Given the improvements in antiretroviral therapy (ART) in recent years, more pediatric HIV patients receiving ART are reaching adolescence and adulthood. This study investigated the influence of poor virological response (low-level viremia (LLV) and virological failure (VF)) on the immune system of these patients. Methods: HIV-infected, ART-experienced pediatric patients (n = 206) were enrolled in this cross-sectional study. The patients were subdivided into school-age children/early adolescents, middle adolescents, and late adolescents/young adults according to their age, and further classified into virological suppression (VS), LLV, and VF groups according to plasma viral load (pVL) measurement. Thymic output, T cells subsets, and immune activation were analyzed by flow cytometry. Results: Compared with VS patients, VF patients displayed decreased CD4+ T cell counts, while LLV and VS patients had comparable CD4+ T cell counts regardless of age. Compared with VS patients, LLV and VF patients had higher percentages of CD8+HLA-DR+ and CD8+CD38high T cells, and the immune activation was positively correlated with pVL in VF and LLV patients. Thymic output levels (CD31+) and regulatory T cell subpopulations in LLV and VF patients were comparable to those in VS patients. LLV patients showed comparable percentages of T cell subsets (TN, TCM, TEMRA, and TEM) as VS patients in all age groups. Conclusions: LLV causes excessive immune activation although it does not impair T cell recovery or naïve-to-memory T cell conversion in pediatric patients living with HIV. Therefore, T cell immune activation should be monitored at the management of LLV during ART. Keywords: Pediatric HIV/AIDS, Antiretroviral therapy, Low-level viremia (LLV), Immune activation, Thymic output

An amendment to this paper has been published and can be accessed via the original article.

Cervical cancer is the second most common cancer in women worldwide and early detection of cervical cancer is crucial to improve the performance of treatment. Autofluorescence arising from cells and tissues can provide information of cellular energy metabolism. Fluorescence lifetime imaging microscopy (FLIM) can be used to detect the metabolism change indicating the development of precancer. In this study, cervical unstained tissue sections obtained from patients were detected by FLIM, which exhibited the cellular morphology features as clear as the pathology images without using fluorescence probes, and the average lifetime of normal tissue samples was consistently lower than that of precancerous or cancerous samples. The results indicate that FLIM is a rapid and label-free tool with high sensitivity and specificity to detect cervical cancer and precancer.

Objectives/Hypothesis Whereas the impression that poor oral hygiene is linked to the development of sialolithiasis may be widely accepted, very few studies provide evidence to support this. This study therefore aimed to evaluate the association between chronic periodontitis (CP) and the subsequent development of salivary gland stone based on a nationwide coverage database. Study Design A case-control study. Methods A total of 987 subjects with sialolithiasis were included as cases. In a ratio of five controls per case, 4,935 controls matched in terms of sex and age group were selected. Conditional logistic regression analysis was performed to determine the possible association of sialolithiasis with previously diagnosed CP. Results The prevalence of prior CP between cases and controls demonstrated that 1,831 (30.9%) out of the 5,922 sampled subjects had prior CP. By Chi-square test, there was a significant difference in the prevalence of prior CP between the cases and controls (36.8% vs. 29.7%, P

Ischemic tolerance is an endogenous protective mechanism that refers to the ability of a sublethal stimulus to induce tolerance to a subsequent lethal ischemic injury. It was first demonstrated in neuronal cells of the gerbil hippocampus (1), after which it has aroused a considerable interest as a possible therapeutic modality for ischemic brain diseases. However, to expose patients to brief periods of ischemia is both impractical and unsafe. Chemical preconditioning substances that can induce ischemic tolerance, such as endotoxins, cytokines, metabolic inhibitors, potassium, chloride, and neurotoxin 3-nitro-propionic acid (1-5) have also been investigated but were found to have limited clinical application due to toxicity and side effects. A variety of experimental models of cerebral ischemia have found that hyperbaric oxygen preconditioning (HBOP) induces ischemic tolerance and attenuates cerebral injury (6-17). Its protective effect is also visible in other conditions leading to oxidative stress, with final anti-apoptotic result, as well as modulation of neutrophin and immune systems (6-17). The blood-brain barrier (BBB), a highly selective permeability barrier, consists of tight junctions (TJ) between capillary endothelial cells, the basal lamina, pericytes, and astrocyte end-feet (18). It plays an important role in maintaining cerebral homeostasis by restricting molecular movement from the cerebral capillaries to the brain tissue. BBB breakdown can result in a vasogenic edema, hemorrhage, and neuronal cell death, all of which can contribute to the pathophysiology of cerebral ischemic diseases (19). TJs between cerebral endothelial cells are formed by complex interactions of cytoskeletal proteins and tight junction proteins (TJPs), including claudins, occludin, zonula occludens (ZO), and cingulin (20). TJPs increase endothelial electrical resistance and decrease paracellular permeability (21). Changes in their expression can lead to the loss of BBB integrity and BBB breakdown (22). HBOP has been associated with reduced brain edema, decreased infarct volume, and improved neurological function (6-17), but it is not clear whether it directly affects the BBB, particularly TJPs expression. This should be clarified in order to find new therapeutic strategies to attenuate BBB permeability in cerebral ischemic disorders. Therefore, the aim of this study was to examine the HBOP effect on hypoxia-induced BBB breakdown in vitro and the changes of occludin and ZO-1 expression.

Patients with risk factors including younger age, mastoiditis, external ear disease, treatment by older surgeons, and concomitant mastoidectomy should receive detailed management to minimize the probability of re-operation for chronic otitis media (COM).Although COM remains a common ear disease requiring surgical intervention, its re-operation risks are less well-documented. This study aimed to compare patients with COM who underwent re-operation and those patients with no re-operation, and identify the risks of re-operation.This retrospective cohort study analyzed the trend of COM surgery from 1999-2009, and identified the re-operation risks of 18 895 patients with COM who underwent surgery from 2002-2006 using the National Health Insurance Research Database in Taiwan.Among the study population, 129 patients underwent revision surgery during a 5.5 ± 1.5 year follow-up period. A univariate logistic regression analysis showed that the re-operation rate was significantly higher in patients under 18 years of age, those with mastoiditis, disorders of external ear, treatment by surgeons of 50-64 years of age, use of a very high volume surgeon, and combined surgery with mastoidectomy. A multivariate analysis further limited the re-operation risk factors to younger patients, those with mastoiditis, external ear disorders, treatment by older surgeons, and concomitant mastoidectomy.

In the above paper, the description of negative control (normal) samples in Section II-A “General tissue samples preparation” was incomplete. The correct and precise description is as following. We sincerely regret the error. For patients who had hysterectomies for benign uterine leiomyoma or adenomyosis, the negative control (normal) samples were obtained from healthy cervix without detectable pathologic change (n=10, Patient No. 1-10).

Rationale: We studied the feasibility of total arathyroidectomy(tPTX)+multi-point transplantation in the forearm for treatment of secondary hyperparathyroidism. Considering the controversial nature of the appropriate timing for and location of this type of surgery, relevant research is relatively rare. Our experience may be a relatively successful one. Patient concerns: Our patient was a 28-year-old woman with end-stage renal disease (ESRD), who was on dialysis for 7 years, and a 2-year history of progressively aggravated bone pain. She also had hypercalcemia and hyperphosphatemia. Diagnoses: Given the patient's history of long-term dialysis, bone pain, high levels of intact parathyroid hormone(i-PTH) and hypercalcemia, we performed ultrasonography which showed solid nodules in the bilateral parathyroid glands. She was accordingly diagnosed with SHPT. Interventions: The patient underwent tPTX+multi-point subcutaneous transplantation in the forearm. Outcomes: Her i-PTH level dropped to < 300 pg/mL, and the symptoms of bone pain markedly reduced after surgery. Lessons: Total parathyroidectomy+multi-point subcutaneous transplantation in the forearm may be a reliable surgical approach for patients with ESRD.

This study aimed to evaluate the relationship between sudden sensorineural hearing loss (SSNHL) and MVP using a population-based dataset. Data for this case-control study were retrieved from the Taiwan Longitudinal Health Insurance Database. In total, 3399 cases of newly diagnosed SSNHL were identified. We used propensity score matching to select 3399 comparison patients (one for every case) from the same dataset. The selected matching variables included age, sex, monthly income, geographical location, urbanization level of the patient's residence, hypertension, diabetes, and hyperlipidemia. Chi-squared tests were used to compare differences in sociodemographic characteristics, while conditional logistic regression analyses were used to examine the association of SSNHL with previously diagnosed MVP. Of the 6798 sampled subjects, 131 (1.93%) patients had received a diagnosis of MVP prior to the index date. A significant difference in the prevalence of prior MVP between cases and controls (2.41% vs. 1.44%, p = 0.004) was observed. The conditional logistic regression analysis conditioned on gender, age, monthly income, urbanization level, geographic region, hyperlipidemia, diabetes, and hypertension suggested that the odds ratio of prior MVP for cases was 1.69 (95% confidence interval (CI): 1.18~2.42) compared to controls. Our study found that patients with MVP had a 1.69-fold higher risk of getting SSNHL compared to patients without MVP.

The relationship between obstructive sleep apnea (OSA) and chronic rhinosinusitis (CRS) still remains unclear. This retrospective cohort study aimed to investigate the relationship between OSA and subsequent CRS using a population-based dataset. The study used data from the Taiwan Longitudinal Health Insurance Database 2005. We selected 971 patients with OSA for the study cohort and 4855 patients without OSA for the comparison cohort. Each patient was tracked for 5 years to determine those who were subsequently diagnosed with CRS. Stratified Cox proportional hazard regression analyses were performed to examine the association of OSA with subsequent CRS. The results revealed that 161 (2.76%) of the total sampled patients were subsequently diagnosed with CRS. Subsequent incidences of CRS were found in 64 (6.59%) patients with OSA and 97 (2.00%) patients without OSA. The adjusted hazard ratio (HR) of subsequent CRS for patients with OSA was 3.18 (95% confidence interval: 2.27~4.45) compared to those without OSA. Furthermore, the HR for CRS was similar for subjects with OSA for both genders (with an adjusted HR of 3.44 for males and 2.63 for females). We concluded that patients with OSA had a higher risk of subsequent CRS compared to patients without OSA regardless of sex.

OBJECTIVE Although plenty of researchers have reported systemic effects originating from chronic periodontitis (CP) on potentially distal inflammatory processes, such as those leading to coronary heart disease, cerebrovascular disease, and cancer, no study has reported the association between CP and sudden sensorineural hearing loss (SSNHL). The present study explored the association between CP and SSNHL using a large, population-based dataset in Taiwan. STUDY DESIGN A case-control study. SETTING Taiwan. PATIENTS We used administrative claims data from the Taiwan National Health Insurance program to identify 2,436 subjects with SSNHL and to randomly select 7,308 controls. MAIN OUTCOME MEASURES A conditional logistic regression analysis was conducted to calculate the odds ratio (OR) for having been previously diagnosed with CP between cases and controls. RESULTS In total, 1,663 (17.1%) of the 9,744 sampled subjects had received a CP diagnosis before the index date; 520 (21.4%) were cases and 1143 (15.6%) were controls. The χ2 test suggested that there was a significant difference in the prevalence of previous SSNHL between cases and controls (p < 0.001). The conditional logistic regression revealed after adjusting for hypertension, diabetes, hyperlipidemia, renal disease, coronary heart disease, obesity, and stroke, the OR of having previously received a CP diagnosis among cases was 1.44 (95% CI = 1.29∼1.63) that of controls. CONCLUSION This study found that SSNHL was significantly associated with a previous diagnosis of CP. Further prospective studies are warranted to confirm our findings and clarify the underlying pathomechanism.

Severe fever with thrombocytopenia syndrome (SFTS), a new disease of zoonotic natural foci has been increasing in recent years. In this review, the disease of human granulocytic anaplasmosis infection due to tickborne and new Bunia virus infection, have similar clinical symptoms. Total of 11 articles were retrieved. The emergence, etiology, nomenclature and pathogenic mechanisms, clinical diagnosis and genotyping of SFTS were summarized, and the current situation of treatment was also evaluated. In conclusion, early detection, identification and treatment are the key points to SFTS, but how to reduce the mortality of critically ill patients is still the focus in the future.

Objectives/Hypothesis Although chronic periodontitis (CP) and chronic rhinosinusitis (CRS) both share immunological disturbances as pathological factors, no prior study has investigated the risk for CP among patients with CRS. This study set out to provide an estimation of risk by utilizing a cohort study design to leverage the statistical power of a population-based dataset in Taiwan. Study Design A retrospective cohort study. Methods In total, 13,782 CRS subjects were included in the study cohort and 41,346 subjects were randomly extracted for the comparison cohort. We individually tracked each subject in this study (N = 55,128) for a 5-year period following their index date to identify those subjects who received a subsequent diagnosis of CP. Cox proportional hazards regression analysis was conducted to calculate the 5-year risk of subsequent CP following a diagnosis of CRS among the sampled subjects. Results The incidence rate of CP during the 5-year follow-up period was 5.12 (95% confidence interval [CI], 4.95-5.30) per 100 person-years and 3.24 (95% CI, 3.17-3.30) per 100 person-years for the study and comparison cohort, respectively. Cox proportional hazards regression revealed that the hazard ratio for CP during the 5-year follow-up period for subjects with CRS was 1.59 times (95% CI, 1.52-1.67) that of comparison subjects after adjusting for monthly income, geographic region, hypertension, diabetes, coronary heart disease, and hyperlipidemia, and censoring for cases who died during the 5-year follow-up period. Conclusions This study detected an increased risk for CP among patients suffering from CRS. CRS patients should be alerted to pay particular attention to their oral hygiene practices to prevent both CP and its downstream sequelae.

Objectives/Hypothesis: It has been recognized that chronic rhinosinusitis (CRS) involves intracranial vessels and may be associated with stroke occurrence. However, the detailed epidemiological profile of stroke risk among patients with CRS is still not well understood. Therefore, this study aimed to explore the frequency and risk for stroke among patients with CRS by conducting a large scale population-based cohort study in Taiwan. Methods: All study cohorts were retrieved from the Taiwan Longitudinal Health Insurance Database. This study included 15,846 CRS subjects in the study cohort and 47,538 randomly selected subjects in the comparison cohort. We individually tracked each subject in this study for a 5 year period following their index dates to identify each subject that received a subsequent diagnosis of stroke. Stratified Cox proportional hazards regressions were analyzed to compare the 5 year risk of subsequent stroke following a diagnosis of CRS. Results: The incidence rate of stroke during the 5-year follow-up period was 10.65 (95% CI: 9.93–11.41) per 100 person years and 7.53 (95% CI: 7.18–7.89) per 100 person years for the study and comparison cohort, respectively. The covariate-adjusted hazard ratio (HR) for stroke revealed that that subjects with CRS were more likely than comparison subjects to have a diagnosis of ischemic stroke during the 5-year follow-up period (HR = 1.34, 95% CI = 1.18–1.53). However, there was no significant difference in the risk of subarachnoid hemorrhage (HR = 1.52, 95% CI = 0.94–2.47) or intracerebral hemorrhage (HR = 0.96, 95% CI = 0.71–1.31). Conclusions: Patients with CRS were at higher risk for stroke occurrence during the 5 year follow-up.