Maternal human papillomavirus infection and the risk of congenital malformations: A nationwide population-based cohort study.

Previous research has explored theories regarding the vertical transmission of human papillomavirus (HPV) infection and its association with adverse pregnancy and perinatal outcomes. However, the impact of maternal HPV infection on congenital anomalies (CAs) in offspring remains relatively understudied. We conducted a population-based cohort study linking the Taiwan Birth Registry, Taiwan Death Registry, and National Health Insurance Research Database, in which newborns born in Taiwan between 2009 and 2015 were included. We established a maternal HPV infection cohort comprising 37 807 newborns and matched them with a comparison group of 151 228 newborns at a 1:4 ratio based on index year, age, and sex. The study examined a composite outcome and subgroups of different types of congenital malformations. Differences in cumulative incidence of CAs were assessed using Kaplan-Meier curves and log-rank tests. Adjusted hazard ratios (aHRs) were estimated using Cox proportional hazard regressions. No significant association was found between HPV infection and the broad spectrum of CAs (aHR: 1.04, 95% confidence interval [CI]: 0.98-1.10; log-rank test p = 0.14). However, we observed a 19% increased risk of musculoskeletal CAs in the maternal HPV infection group (aHR: 1.19; 95% CI: 1.05-1.34) compared to those without maternal HPV exposure. Other factors, including the type of HPV (aHR: 0.65; 95% CI: 0.16-2.63), the timing of exposure (during or before pregnancy), and maternal age (aHR for <30 years: 1.02, 95% CI: 0.94-1.1; aHR for 30-39 years: 1.05, 95% CI: 0.99-1.11; aHR for ≥40 years: 0.88, 95% CI: 0.67-1.17), did not significantly affect the risk for any CA. In conclusion, gestation detection of HPV infection was associated with musculoskeletal CAs but not other major CAs. Prospective studies are warranted to elucidate the necessity of prenatal screening in populations at risk.

Recent Human Papillomavirus Vaccination is Associated with a Lower Risk of COVID-19: A US Database Cohort Study.

OBJECTIVE: To explore the association between human papillomavirus (HPV) vaccination and risk of coronavirus disease 2019 (COVID-19). Specifically, our study aimed to test the hypothesis that HPV vaccination may also induce trained immunity, which would potentially reduce the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and improve clinical outcomes. BACKGROUND: Several vaccines have been reported to trigger non-specific immune reactions that could offer protection from heterologous infections. A recent case report showed that verruca vulgaris regressed after COVID-19, suggesting a possible negative association between COVID-19 and HPV infection. METHODS: We enrolled 57,584 women with HPV vaccination and compared them with propensity score-matched controls who never received HPV vaccination in relation to the risk of COVID-19 incidence. Cox proportional hazard regression analysis was conducted to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Subgroup analyses stratified by age, race, comorbid asthma, and obesity were performed. RESULTS: The risk of COVID-19 incidence was significantly lower in those who had recently received the HPV vaccine (within 1 year after HPV vaccination, aHR: 0.818, 95% CI 0.764-0.876; within 1-2 years after HPV vaccination, aHR: 0.890, 95% CI 0.824-0.961). Several limitations were recognized in this study, including residual confounding, problems of misclassification due to the use of electronic health record data, and that we were unable to keep track of the patients' HPV infection status and the HPV antibody levels in those who had received the vaccine. CONCLUSIONS: Recent HPV vaccination was associated with a lower risk of incident COVID-19 and hospitalization. Based on the promising protective effect of HPV vaccine shown in this study, these findings should be replicated in an independent dataset. Further studies are needed to provide a better understanding of the underlying mechanisms and the differences in risks among 2-, 4-, or 9-valent HPV vaccine recipients.

Absence of an association between gastrointestinal tract surgery and newly diagnosed psoriasis: A nationwide, population-based, nested, case-control study.

BACKGROUND: Gastrointestinal tract surgeries could disrupt the microbiome and simultaneously cause trauma, which may result in psoriasis. OBJECTIVE: To examine associations between gastrointestinal tract surgeries and newly diagnosed psoriasis. METHODS: This nested case-control study included patients with newly diagnosed psoriasis from 2005 to 2013, retrieved from the Taiwan National Health Insurance Research Database. We retrospectively (5 years from the index date) determined whether the patients had undergone gastrointestinal tract surgery. RESULTS: We identified 16 655 patients with newly diagnosed psoriasis and matched 33 310 individuals as the control group. The population was stratified by age and sex. There was no association between age and psoriasis (<20 years: adjusted odds ratio [aOR] 0.80, 95% confidence interval [CI] 0.52-1.24; 20-39 years: aOR 1.09, 95% CI 0.79-1.51; 40-59 years: aOR 0.89, 95% CI 0.57-1.39; ≥60 years: aOR 0.82, 95% CI 0.54-1.26). Similar findings were obtained by sex, with no differences among men (aOR 0.90, 95% CI 0.69-1.17) and women (aOR 0.96, 95% CI 0.71-1.29). CONCLUSION: Our study indicates that gastrointestinal surgeries have limited age- and sex-related effects on psoriasis. These findings provide new insights into the risk of developing psoriasis.

Nontyphoidal Salmonella Infection Associated with Subsequent Risk of Hematological Malignancies: A Nationwide Population-Based Cohort Study.

This study aimed to investigate the relationship between nontyphoidal salmonellosis (NTS) and new-onset hematological malignancy. We conducted a 17-year nationwide, population-based, retrospective cohort study to examine the association between NTS and the risk of hematological malignancies by using the Longitudinal Health Insurance Database (LHID) of Taiwan. Participants were enrolled from 2000 to 2015 and were monitored until 2017. We traced the years 1998-2000 to ensure that the cases included were newly diagnosed with NTS. The NTS cohort included 13,790 patients with newly diagnosed NTS between 2000 and 2015. Each patient was propensity score matched at a 1:4 ratio with people without NTS. Cumulative incidence, hazard ratios (HRs), and 95% confidence intervals (CIs) were calculated after adjusting for age, sex, income, urbanization, and medical comorbidities. The adjusted hazard ratio (aHR) of hematological malignancies for NTS patients relative to those without NTS was 1.42 (95% CI 0.91-2.20). In the age subgroup analysis, NTS had a significantly greater risk of hematological malignancies for patients older than 60 (aHR 3.04, 95% CI 1.46-6.34), with an incidence rate of 11.7 per 10,000 person-years. In patients over 60 years of age, a prominent risk of hematological malignancies was observed at a follow-up of more than 3 years after the index date (aHR 3.93, 95% CI 1.60-9.65). A history of NTS is associated with the risk of subsequent hematological malignancies in Taiwanese subjects older than 60.

Association between human papillomavirus infection and sudden sensorineural hearing loss: A nationwide population-based cohort study.

Background: While the etiology of sudden sensorineural hearing loss (SSNHL) remains unclear, viral infection has been suggested as a possible cause. Human papillomavirus (HPV) might trigger immune-mediated reaction and induce inflammatory cytokines which are injurious to the cochlea. This study aimed to investigate the association between HPV infection and the risk of developing SSNHL using a nationwide population-based data set. Methods: In this study, we used the population-based National Health Insurance Research Database of Taiwan to enroll 49,247 individuals with HPV infection from January 1st, 2000, to December 31st, 2013, and compared with a control group of 98,494 individuals who had never been diagnosed with HPV infection (at a 1:2 ratio matched by age, sex, index year, and comorbidities) in relation to the risk of subsequent SSNHL. The primary outcome was the time from the index date to the date when the first diagnosis of SSNHL occurred, death, withdrawal from the National Health Insurance Program, or the end of the study. Cox model with frailty was conducted to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), relative to comparison group. Sensitivity analyses were performed to validate our findings. Findings: The adjusted hazard ratio (aHR) of developing SSNHL was 1.37 (95% CI, 1.07-1.74) after adjustment for demographic characteristics, comorbidities, and medications. Sensitivity analyses showed consistent positive association. In our sub-group analysis, a significantly higher effect of HPV on SSNHL was noted in the patients with a previous diagnosis of cerebrovascular disease, compared with those without cerebrovascular disease (aHR: 4.59 versus 1.27, p-value for interaction = 0.024). Interpretation: HPV infections are associated with higher risk of subsequent SSNHL in the Taiwanese population. More research is needed to examine the causality and to determine the potential efficacy of specific precautions. Funding: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Human Papillomavirus Infection and the Risk of Erectile Dysfunction: A Nationwide Population-Based Matched Cohort Study.

BACKGROUND: Male patients with genital warts are known for higher rates of sexual dysfunction. This study was conducted to investigate whether human papillomaviruses (HPV) infection is associated with an increased risk of erectile dysfunction (ED). METHODS: Patients aged over 18 with HPV infection (n = 13,296) and propensity score-matched controls (n = 53,184) were recruited from the Longitudinal Health Insurance Database (LHID). The primary endpoint was the diagnosis of ED. Chi-square tests were used to analyze the distribution of demographic characteristics. The Cox proportional hazards regression was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the development of ED in both groups, after adjusting for sex, age, relevant comorbidities, co-medication, and surgery. RESULTS: ED developed in 181 patients of the study group. The incidence density of ED was 2.53 per 1000 person-years for the HPV group and 1.51 per 1000 person-years for the non-HPV group, with an adjusted HR (95% CI) of 1.63 (1.37-1.94). In stratification analysis, adjusted HR of diabetes-, chronic obstructive pulmonary disease (COPD-), and stroke-subgroup were 2.39, 2.51, and 4.82, with significant p values for interaction, respectively. Sensitivity analysis yields consistent findings. CONCLUSIONS: The patients with HPV infection had a higher risk of subsequent ED in comparison to the non-HPV controls. The mechanism behind such association and its possible role in ED prevention deserves further study in the future.

Human Papillomavirus Infection Is Associated with Decreased Risk of Hepatocellular Carcinoma in Chronic Hepatitis C Patients: Taiwan Nationwide Matched Cohort Study.

Background: Hepatitis C virus (HCV) has been shown to be associated with human papillomavirus (HPV)-positive head and neck cancers. However, studies regarding HPV infection and the risk of new-onset hepatocellular carcinoma (HCC) among chronic hepatitis C (CHC) patients are limited. We examined the risk of HCC in CHC patients with or without HPV infection. Methods: In total, 9905 CHC patients from 2000 to 2016 constituted the whole cohort. HPV was defined as being diagnosed after HCV. The CHC cohort with HPV (N = 1981) and age-, sex-, inception point-, comorbidity-, and medication-matched non-HPV (N = 7924) were followed up until HCC, death, or 2018. HCC patients were extracted from the Taiwan Registry for Catastrophic Illness Database. We adopted the propensity score match and inverse probability of treatment weighting (IPTW) to eliminate bias. Cox proportional hazard regression analyses were performed to calculate HCC risk. Results: After a full adjustment, HPV was not associated with HCC risk (aHR, 0.74; 95% CI, 0.58−0.96 in the main model, and aHR, 0.76; 95% CI, 0.66−0.87 in IPTW, respectively). Almost all subgroup analyses verified this finding (HRs < 1.0). Conclusions: Among CHC patients older than 18 years old, those with HPV infection were associated with a lower risk of subsequent HCC.

The Potential Role of Human Papillomavirus Infection in Bell's Palsy: A Hypothesis-Generating Study Based on a Nationwide Cohort.

Objective: Our purpose was to investigate whether people with a previous human papillomavirus (HPV) infection were associated with an increased risk of Bell's palsy (BP). Methods: By using Taiwan population-based data, patients aged > 18 years with HPV infection (n = 22,260) from 2000 to 2012 were enrolled and compared with control subjects who had never been diagnosed with an HPV infection at a 1:4 ratio matched by sex, age, index date, and co-morbidities (n = 89,040). The index date was the first date of HPV diagnosis. All the patients were tracked until the occurrence of BP. Cox proportional hazards regression was applied to estimate the hazard ratios (HRs) for the development of BP in both groups. Results: The HPV group had 1.25 [95% confidence interval (CI) = 1.03-1.51] times higher risk of BP compared with the non-HPV group after adjusting for sex, age, and co-morbidities. The association of HPV and BP was significant in the sensitivity analyses. In the subgroup analysis, the impact of HPV infection on the risk of BP was more pronounced in the elderly > 50 years [adjusted hazard ratio (aHR) =1.86; 95% CI = 1.37-2.52], hypertension (aHR = 1.65; 95% CI = 1.17-2.31), and chronic obstructive pulmonary disease (aHR = 2.14, 95% CI 1.333.43) subgroups. Conclusions: Patients with HPV infection have a higher risk of subsequent BP compared with non-HPV patients. More rigorous studies are needed to confirm if and how specific HPV genotypes are associated with BP and the possible role of vaccines in disease prevention.

Risk of subsequent atrial fibrillation in patients with myasthenia gravis: A population-based cohort study.

ABSTRACT: The purpose of this study was to explore the association between myasthenia gravis (MG) and the risk of atrial fibrillation (AF) in an Asian population. The risk was analyzed in a cohort of 5528 patients with history of MG and 5528 individuals without MG using a hospitalization claim dataset. Both groups were matched by age, sex, index year and baseline comorbidities as an original analysis. A Cox proportional hazard model was used to estimate the hazard ratio and 95% confidence interval of AF after adjusting for demographic and relevant clinical covariates. The adjusted hazard ratio of the MG group compared with that of the non-MG group was 1.03 (95% confidence interval, 0.76-1.38) for AF. A stratified analysis showed that compared with the propensity score matched non-MG group, there was no increased risk of developing AF based on age categories, gender, or comorbidities. Different time follow-up periods results showed no increased risk of AF compared with the non-MG group. Overall, in the Taiwanese cohort, MG is not associated with an increased risk of AF.

Human papillomavirus symptomatic infection associated with increased risk of new-onset alopecia areata: A nationwide population-based cohort study.

BACKGROUND: We investigated the correlation between a history of human papillomavirus (HPV) infection and alopecia areata risk. METHODS: The study cohort comprised 30,001 patients with newly diagnosed HPV infection between 2000 and 2012; and with use of computer-generated randomly numbers, patients not had HPV infection were randomly selected as the comparison cohort. HPV infection cohort were matched to comparison individuals at a 1:1 ratio by age, gender and index year. All study individuals were followed up until they developed alopecia areata, withdraw from the insurance program, lost to follow-up, or until the end of 2013. Cox proportional hazards regression analysis was used to analyze the risk of alopecia areata with hazard ratios (HRs) and 95% confidence intervals (CIs) between the HPV and control cohort. RESULTS: The adjusted hazard ratio (aHR) of alopecia areata for HPV patients relative to controls was 2.55 (95% C.I. = 1.88-3.47) after adjusting sex, age and comorbidities. Subgroup analysis indicated that patients with HPV infections had a significantly greater risk of alopecia areata for both genders, all age subgroups, and those with mental disorder diseases. CONCLUSIONS: A history of HPV infection is associated with the development of subsequent alopecia areata in Taiwanese subjects.

Tumor subsites and risk of osteoradionecrosis of the jaw in patients with oral cavity cancer: a national-based cohort study.

PURPOSE: The association between the tumor subsites of the oral cavity and the risk of osteoradionecrosis of the jaw (ORNJ) remains unclear. We study the correlation between oral cavity tumor subsites and the risk of ORNJ in a nationwide population-based database. METHODS: We enrolled 16,701 adult patients with oral cavity cancers who were treated with radiotherapy between 2000 and 2013. The subsites of the oral tumor, treatments of oral cavity cancers, and the timing of tooth extraction were examined for their association with ORNJ in oral cancer patients. RESULTS: 903 patients (5.40%) developed ORNJ. Of the relevant variables, pre-RT mandible surgery, tooth extraction either before or after RT, and tumor sites were associated with the risk of ORNJ. The adjusted HRs for ORNJ in the mouth floor, gums, retromolar, and buccal cancer were 2.056 (1.490-2.837), 1.909 (1.552-2.349), 1.683 (1.105-2.562), and 1.303 (1.111-1.528), respectively, compared with the risk of tongue cancer. There was no significant difference in the risk of ORNJ between the pre-RT extraction group, the during-RT extraction group, and the post-RT extraction (less than 6 months) group; the post-RT extraction (more than 6 months) group had a significantly higher risk of ORNJ. CONCLUSIONS: This study demonstrated that oral cavity tumor subsite is an independent risk factor of ORNJ after RT. Post-RT extraction (less than 6 months) group did not carry a significantly higher risk of ORNJ compared with pre-RT extraction group or during RT extraction group.

The potential role of nontyphoidal salmonellosis in gastric cancer: a nationwide matched cohort study.

BACKGROUND: The research is to explore the association between nontyphoidal salmonellosis (NTS) and subsequent gastric cancer. METHODS: We conducted a retrospective study by analyzing hospitalization dataset from the National Health Insurance Research Database in Taiwan. Patients aged 20 years and older with NTS (n = 9 097) admitted between January 1, 2000, and December 31, 2012, were enrolled and followed up until December 31, 2013. The primary outcome was the incidence of gastric cancer. Cox proportional hazards regression was used to estimate the risk of malignancy, accounting for the competing risk of death. In addition, we conducted a sensitivity analysis by propensity score matching and exclusion of malignancy within 1 year observation to minimize measurable confounding and protopathic bias. Negative controls were applied to examine the presence of possible unmeasured confounders in the study. RESULTS: The study included 18 194 patients (9097 in each NTS and non-NTS group). The median follow-up time was 7 years. The incidence density rate of gastric cancer was 0.72 per 1000 person-years for the NTS group and 0.40 per 1000 person-years for the non-NTS group. The NTS group had a modestly higher risk of gastric cancer (aHR, 2.02; 95% CI 1.18-3.45) than the non-NTS group. The sensitivity analyses revealed consistent results. CONCLUSIONS: Patients with NTS are associated with increased risk of subsequent gastric cancer compared with non-NTS patients. Future research is needed to examine whether NTS is parallel, reactive or causative to gastric cancer.

The Impact of Human Papillomavirus Infection on Skin Cancer: A Population-Based Cohort Study.

BACKGROUND: This study investigated the correlation between a history of human papillomavirus (HPV) infection and skin cancer risk. MATERIALS AND METHODS: The study cohort comprised 26,919 patients with newly diagnosed HPV infection between 2000 and 2012; with the use of computer-generated numbers, patients without previous HPV infection were randomly selected as the comparison cohort. The patients in the HPV infection cohort were matched to comparison individuals at a 1:4 ratio by demographic characteristics and comorbidities. All study individuals were followed up until they developed skin cancer, withdrew from the National Health Insurance program, were lost to follow-up, or until the end of 2013. The primary outcome was subsequent skin cancer development. Cox proportional hazards regression analysis was used to analyze the risk of skin cancer with hazard ratios (HRs) and 95% confidence intervals (CIs) between the HPV and control cohort. RESULTS: The adjusted HR of skin cancer for patients with HPV relative to controls was 2.45 after adjusting sex, age and comorbidities. (95% CI, 1.44-4.18, p < .01). The subgroup analysis indicated that a patient with HPV infection had a significantly greater risk of skin cancer if they were aged >40 years. Notably, a risk of skin cancer was found in the group diagnosed with HPV within the first 5 years after the index date (adjusted HR, 3.12; with 95% CI, 1.58-5.54). Sensitivity analysis by propensity score, matching with balanced sex, age, and comorbidities, showed consistent results. CONCLUSION: A history of HPV infection is associated with the development of subsequent skin cancer in Taiwanese subjects, and the risk wanes 5 years later. IMPLICATIONS FOR PRACTICE: In this Taiwan nationwide cohort study, there was a 2.45-fold increased risk of developing new-onset skin cancers for patients with incident human papillomavirus (HPV) infection, compared with the matched controls. Furthermore, the risk was noticeably significant among patients aged >40 years. A prominent risk of skin cancers was found in the group diagnosed with HPV within the first 5 years after the index date in this study. The results of this analysis may raise consensus on the effect of HPV infection on the risk of skin cancers. Clinicians are encouraged to implement prudently on the differential diagnosis of skin cancers and HPV prevention and treatment, especially in older patients.

Association of Infection With Human Papillomavirus and Development of End-Stage Kidney Disease in Taiwan.

Importance: The association between human papillomavirus (HPV) infection status and the natural process of kidney diseases has been neglected as an area of research. Further studies are needed to clarify factors that may alter the progression of end-stage kidney disease (ESKD). Objective: To describe the rates of ESKD among patients with and without HPV infection. Design, Setting, and Participants: In this nationwide, population-based retrospective cohort study, data were collected from the National Health Insurance Research Database of Taiwan. A total of 76 088 individuals with HPV infection were enrolled from January 1, 2000, to December 31, 2012, and compared with a control group of 76 088 individuals who had never been diagnosed with HPV infection (at a 1:1 ratio propensity-score matched by age, sex, index year, and comorbidities) in the context of the risk of developing ESKD. Statistical analysis was performed between November 2019 and July 2020. Exposures: HPV infection was defined according to the International Classification of Diseases, Ninth Revision, Clinical Modification codes. Main Outcomes and Measures: The main outcome was ESKD, as recorded in the Catastrophic Illness Patients database. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs, with the control group as a reference. Results: Of 152 176 individuals (79 652 [52.3%] women; mean [SD] age, 34.4 [19.1] years), 76 088 individuals (50.0%) had HPV and 463 individuals (0.3%) developed ESKD. Incidence of ESKD was lower in individuals with HPV history than in those without HPV history (3.64 per 10 000 person-years vs 4.80 per 10 000 person-years). In the fully adjusted multivariate Cox proportional hazards regression model, individuals with a history of HPV infection had a significant decrease in risk of ESKD (adjusted HR, 0.72; 95% CI, 0.60-0.87) after adjusting for demographic characteristics, comorbidities, and comedications. In the subgroup analysis, individuals ages 50 to 64 years with HPV infection had a statistically significantly lower risk of ESKD compared with individuals ages 50 to 64 years with no HPV infection (adjusted HR, 0.48; 95% CI, 0.34-0.68; P < .001), while there was no significant reduction in risk for the other age groups (ie, 0-19, 20-49, and 65-100 years). Conclusions and Relevance: In this study, a history of HPV infection was associated with a lower risk of subsequent ESKD. The mechanism behind this protective association remains uncertain. Future studies are required to clarify the possible biological mechanisms.

Female Human Papillomavirus Infection Associated with Increased Risk of Infertility: A Nationwide Population-Based Cohort Study.

OBJECTIVE: This study investigated whether women with a history of human papillomavirus (HPV) infection have an increased risk of infertility. MATERIAL AND METHODS: All patients with an HPV infection (n = 11,198) in Taiwan's National Health Insurance Research Database (2000-2012) were propensity score matched with control subjects (n = 11,198) without an HPV infection by age, sex, index year, and relevant co-morbidities. Both groups were tracked until a diagnosis of infertility was recorded. The Chi-square test was used to analyze the distribution of demographic characteristics in the HPV group and non-HPV group. A Cox proportional hazards regression was used to estimate the hazard ratios (HRs) for the development of infertility, adjusting for age, sex, and co-morbidities. The Kaplan-Meier method was used to plot the cumulative incidence curves. We also performed negative controls to test for possible unmeasured confounding. RESULTS: The HPV cohort had a higher risk of infertility. The adjusted HR (aHR) was found to be 1.39 (95% CI = 1.19-1.63) after adjusting for demographic characteristics and relevant co-morbidities. In the age subgroup analysis, patients with an HPV infection had an increased risk of infertility compared to the non-HPV cohort in the group aged 26 to 35 years (aHR, 1.53; 95% CI = 1.24-1.88). As we used propensity score matching to treat measurable confounders and negative controls to access unmeasured confounders, the findings of the study are robust. CONCLUSIONS: Among females of reproductive age, HPV infection is a potential risk factor that predisposes individuals to subsequent infertility.

Risk of subsequent ischemic stroke in patients with nontyphoidal salmonellosis: A nationwide population-based cohort study.

OBJECTIVES: To explore the association between nontyphoidal salmonellosis (NTS) and the risk of acute ischemic stroke (IS) by using a nationwide, population-based study. METHODS: A retrospective cohort study using claim data from Taiwan's National Health Insurance Research Database (NHIRD), patients aged 18 years and older with histories of NTS (N = 1618) were included from January 1, 2000-December 31, 2012, and the non-NTS group (N = 6472) without NTS were matched by propensity score. The follow-up period was defined as the time from the initial diagnosis of NTS to the date of development of IS, death or 31 December, 2013. Patients previously diagnosed with stroke were excluded. The Cox proportional hazard model with robust sandwich estimator was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) of IS after adjusting for demographic and clinical covariates. RESULTS: The adjusted hazard ratio (aHR) for the NTS group compared with the non-NTS group was 1.34 (95% confidence interval [CI], 1.10-1.65) for overall stroke. Furthermore, the NTS cohort had an increased risk of IS compared to the non-NTS groups (aHR, 1.42; 95% CI, 1.14-1.78). Stratified analysis showed that compared with propensity score matched non-NTS group, subjects aged ≥65 years, female, those with hypertension, hyperlipidemia, COPD, cancer and heart failure had higher risk of developing stroke. A 1.93-fold significant increase risk for stroke was observed during the first 3-12 months of follow-up (95% CI, 1.07-3.48). CONCLUSIONS: Patients with NTS is associated with increased risk of developing ischemic stroke compared with non-NTS patients. Timely and mindful treatment plan about NTS may be a milestone to stroke prevention especially in some subpopulation.

Continuity of Care Is Associated with Medical Costs and Inpatient Days in Children with Cerebral Palsy.

Background: Children with cerebral palsy (CP) place a considerable burden on medical costs and add to an increased number of inpatient days in Taiwan. Continuity of care (COC) has not been investigated in this population thus far. Materials and Methods: We designed a retrospective population-based cohort study using Taiwan's National Health Insurance Research Database. Patients aged 0 to 18 years with CP catastrophic illness certificates were enrolled. We investigated the association of COC index (COCI) with medical costs and inpatient days. We also investigated the possible clinical characteristics affecting the outcome. Results: Over five years, children with CP with low COCI levels had higher medical costs and more inpatient days than did those with high COCI levels. Younger age at CP diagnosis, more inpatient visits one year before obtaining a catastrophic illness certificate, pneumonia, and nasogastric tube use increased medical expenses and length of hospital stay. Conclusions: Improving COC reduces medical costs and the number of inpatient days in children with CP. Certain characteristics also influence these outcomes.