Prior COVID-19 vaccination and reduced risk of cerebrovascular diseases among COVID-19 survivors.

The effects of COVID-19 vaccination on short-term and long-term cerebrovascular risks among COVID-19 survivors remained unknown. We conducted a national multi-center retrospective cohort study with 151 597 vaccinated and 151 597 unvaccinated COVID-19 patients using the TriNetX database, from January 1, 2020 to December 31, 2023. Patients baseline characteristics were balanced with propensity score matching (PSM). The outcomes were incident cerebrovascular diseases occurred between 1st and 30th days (short-term) after COVID-19 diagnosis. Nine subgroup analyses were conducted to explore potential effect modifications. We performed six sensitivity analyses, including evaluation of outcomes between 1st to 180th days, accounting for competing risk, and incorporating different variant timeline to test the robustness of our results. Kaplan-Meier curves and Log-Rank tests were performed to evaluate survival difference. Cox proportional hazards regressions were adopted to estimate the PSM-adjusted hazard ratios (HR). The overall short-term cerebrovascular risks were lower in the vaccinated group compared to the unvaccinated group (HR: 0.66, 95% CI: 0.56-0.77), specifically cerebral infarction (HR: 0.62, 95% CI: 0.48-0.79), occlusion and stenosis of precerebral arteries (HR: 0.74, 95% CI: 0.53-0.98), other cerebrovascular diseases (HR: 0.57, 95% CI: 0.42-0.77), and sequelae of cerebrovascular disease (HR: 0.39, 95% CI:0.23-0.68). Similarly, the overall cerebrovascular risks were lower in those vaccinated among most subgroups. The long-term outcomes, though slightly attenuated, were consistent (HR: 0.80, 95% CI: 0.73-0.87). Full 2-dose vaccination was associated with a further reduced risk of cerebrovascular diseases (HR: 0.63, 95% CI: 0.50-0.80) compared to unvaccinated patients. Unvaccinated COVID-19 survivors have significantly higher cerebrovascular risks than their vaccinated counterparts. Thus, clinicians are recommended to monitor this population closely for stroke events during postinfection follow-up.

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.

Acarbose might be associated with reduced risk of gastric cancer in patients with diabetes mellitus: A nationwide population-based cohort study.

BACKGROUND: Several epidemiologic studies have revealed a higher risk of cancer in patients with diabetes mellitus (DM) relative to the general population. To investigate whether the use of acarbose was associated with higher/lower risk of new-onset cancers. METHOD: We conducted a retrospective cohort study, using a population-based National Health Insurance Research Database of Taiwan. Both inpatients and outpatients with newly onset DM diagnosed between 2000 and 2012 were collected. The Adapted Diabetes Complications Severity Index (aDCSI) was used to adjust the severity of DM. The Cox proportional hazards regression model was used to estimate the hazard ratio (HR) of disease. RESULTS: A total of 22 502 patients with newly diagnosed DM were enrolled. The Cox proportional hazards regression model indicating acarbose was neutral for risk for gastroenterological malignancies, when compared to the acarbose non-acarbose users group. However, when gastric cancer was focused, acarbose-user group had significantly lowered HR than non-acarbose users group (p = 0.003). After adjusted for age, sex, cancer-related comorbidity, severity of DM, and co-administered drugs, the HR of gastric cancer risk was 0.43 (95% CI = 0.25-0.74) for acarbose-user patients. CONCLUSION: This long-term population-based study demonstrated that acarbose might be associated with lowered risk of new-onset gastric cancer in diabetic patients after adjusting the severity of DM.

Interaction between alimentary surgery and risk of dementia: a nationwide population-based case-control study.

BACKGROUND: Based on current research, it is known that the gastrointestinal tract microbiota and its genome play a crucial role in mental illnesses. Studies indicate a direct correlation between gastrointestinal tract microbiota and the onset of dementia, mediated by metabolic diseases and low-grade inflammation. The association between various gastrointestinal symptoms and neurodegenerative diseases has been recently discussed. However, there is a lack of research regarding the comparative effects of different surgical procedures on neurodegenerative diseases. Therefore, this study primarily focuses on comparing the association between various gastrointestinal surgeries and dementia, aiming to provide guidance for future clinical practice. METHOD: A nationwide study using the Taiwanese National Health Insurance Research Database included 26 059 patients diagnosed with dementia or Alzheimer's disease and 104 236 controls without diseases. Primary exposures were defined as alimentary surgeries, encompassing cholecystectomy, gastrectomy, bowel resection, and appendectomy. Conditional logistic regression was used to examine the odds ratio and 95% confidence interval for prior alimentary surgery between cases and controls. RESULTS: The results showed that individuals with dementia had a higher rate of gastrectomy. Additionally, individuals with dementia seemed to exhibit a reduced rate of cholecystectomy and appendectomy. Regarding Alzheimer's disease, all four alimentary surgeries showed comparable trends to those observed with dementia. No significant interaction was observed between alimentary surgery and dementia among the four types of surgery evaluated. CONCLUSION: Our study demonstrates that gastrectomy is associated with an elevated risk of dementia. We aim to uncover more direct evidence in future experiments.

Association of diverticulitis and potential risk of ischemic stroke: population-based matched cohort study in Taiwan.

BACKGROUND: Previous studies have suggested relationship between diverticular disease and cardiovascular disease. Since cardiovascular disease and cerebrovascular accident share a lot of pathogenesis, diverticulitis could also be a risk factor for stroke. This study tried to establish epidemiological evidence of the relationship between colon diverticulitis and ischemic stroke. METHODS: In this retrospective cohort study, patients with newly diagnosed colon diverticulitis (N = 6238) and patients without colon diverticulitis (control group; N = 24 952) were recruited between January 1, 2000, and December 31, 2017. Both groups were matched by propensity score at a 1:4 ratio by age, sex, comorbidities and medications. Cox proportional hazard regression was applied to estimate the hazard ratio (HR) and 95% confidence interval (CI) of ischemic stroke. We also conducted 4 different regression models and 2 sensitivity analyses to test the robustness of our findings. RESULTS: The diverticulitis group had a higher risk of IS than the control group (adjusted HR, 1.25; 95% CI, 1.12-1.39; P < 0.001). Serial sensitivity analyses yielded consistent positive link between diverticulitis and IS. Further subgroup analysis showed that in the study group, the risk of IS was 2.54-fold higher than the matched controls in 30-39 years. CONCLUSIONS: Our study found that colon diverticulitis was associated with a higher risk of developing subsequent ischemic stroke, especially for patients aged 30-39 years, among Asian population. This result provides us a chance to undertake preventive measures for ischemic stroke in high-risk patients.

Time-dependent risk of atopic dermatitis following nontyphoidal Salmonella infection.

BACKGROUND: The pathogenesis of atopic dermatitis (AD) remains unclear. Nontyphoidal Salmonella (NTS) infection might trigger immune-mediated reactions. We aimed to examine NTS and the risk of subsequent AD. METHODS: From 2002 to 2015, eligible patients (aged 0-100 years) with NTS were identified. NTS and non-NTS groups were matched at a 1:10 ratio on age and sex. We utilized conditional multivariable Cox proportional hazard models to estimate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) for AD development. Subgroup analyses were conducted based on age, sex, and severity of NTS infection. We utilized landmark analysis to explore the time-dependent hazard of AD following NTS. RESULTS: In the NTS group (N = 6624), 403 developed AD. After full adjustment of demographics and comorbidities, the NTS group had a higher risk of AD than the reference group (aHR = 1.217, 95% CI = 1.096-1.352). Age-stratified analysis revealed that NTS group exhibited an elevated risk compared to the reference group, particularly among those aged 13-30 years (aHR = 1.25, 95% CI = 1.017-1.559), individuals aged 31-50 years (aHR = 1.388, 95% CI = 1.112-1.733), those aged 51-70 years (aHR = 1.301, 95% CI = 1.008-1.679), and individuals aged 71 years and over (aHR = 1.791, 95% CI = 1.260-2.545). Severe NTS was associated with a higher risk of AD than the reference group (aHR = 2.411, 95% CI = 1.577-3.685). Landmark analysis showed generally consistent findings. CONCLUSIONS: Minimizing exposure to NTS infection may represent a prospective strategy for averting the onset and progression of atopic dermatitis.

Patients with obstructive sleep apnea are at great risk of flavor disorders: a 15-year population-based cohort study.

OBJECTIVE: Obstructive sleep apnea (OSA) results from upper airway remodeling, which has been suggested to alter sensory and motor neuron function due to hypoxia or snore vibration. This study investigated whether OSA was associated with the risk of flavor disorder (FD). MATERIALS AND METHODS: Seven thousand and eight hundred sixty-five patients with OSA and 7865 propensity score-matched controls without OSA were enrolled between 1999 and 2013 through a nationwide cohort study. The propensity score matching was based on age, sex, comorbidities including hypertension, hyperlipidemia, chronic obstructive pulmonary disease (COPD), asthma, ankylosing spondylitis, and Charlson comorbidity index, and co-medications during the study period, including statins and angiotensin-converting enzyme (ACE) inhibitors. The adjusted hazard ratio (aHR) of incident FD following OSA was derived using a Cox proportional hazard model. A log-rank test was used to evaluate the time-dependent effect of OSA on FD. Age, sex, comorbidities, and co-medications were stratified to identify subgroups susceptible to OSA-associated FD. RESULTS: Patients with OSA were at a significantly great risk of FD (aHR = 1.91, 95% CI = 1.08-3.38), which was time-dependent (log-rank test p = 0.013). Likewise, patients with hyperlipidemia were at a significant great risk of FD (aHR = 2.99, 95% CI = 1.33-6.69). Subgroup analysis revealed that female patients with OSA were at higher risks of FD (aHR = 2.39, 95%CI = 1.05-5.47). CONCLUSIONS: Patients with OSA were at significantly great risk of incident FD during the 15-year follow-up period, especially in female patients with OSA. CLINICAL RELEVANCE: Timely interventions for OSA may prevent OSA-associated FD.

Newly Diagnosed Leptospirosis and Subsequent Hemorrhagic Stroke: A Nationwide Population-Based Cohort Study.

BACKGROUND AND PURPOSE: Preceding infection as an important risk factor for ischemic stroke has been reported but neglected for hemorrhagic stroke, especially in young and middle-aged patients. This study investigates whether newly diagnosed leptospirosis is associated with an increased risk of stroke. METHODS: We identified 3699 in-patients who were aged ≥18 years and newly diagnosed with leptospirosis. We also randomly selected a comparison cohort 14 796 in-patients from the general population by using a propensity score matching method (at a 1:4 ratio). We analyzed the risks of stroke by using Cox proportional hazard regression models. RESULTS: The adjusted hazard ratio (HR; 95% CI) of stroke for the leptospirosis group was 1.14 (0.93-1.38; P=0.200) as opposed to the comparison group after adjusting sex, age, and comorbidities. However, adjusted HR (95% CI) of ischemic stroke and hemorrhagic stroke was 1.01 (0.80-1.29) and 1.58 (1.12-2.23), respectively. The strength of association between leptospirosis and hemorrhagic stroke remained statistically significant after variation of leptospirosis and stroke definitions. The post hoc subgroup analysis indicated that a patient with leptospirosis had a significantly greater risk of hemorrhagic stroke in male (adjusted HR, 1.62 [95% CI, 1.08-2.44]) and individuals between age 18 and 39 (adjusted HR, 3.67 [95% CI, 1.33-10.14]). The risk of hemorrhagic stroke among people with leptospirosis was highest in the first 2 years after diagnosis (adjusted HR, 1.97 [95% CI, 1.15-3.38]). CONCLUSIONS: A 2.49-fold risk of stroke was found among the leptospirosis cohort of aged younger than 39 years. Age acted as an effect modifier between the leptospirosis and risk of new-onset stroke.

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.

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.

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.

Increased risk of glaucoma amongst new-onset gout patients aged 20-39 years: A nationwide population-based cohort study in Taiwan.

OBJECTIVES: To provide epidemiologic evidence of whether gout increases the risk of new-onset glaucoma. METHODS: We conducted a 13-year nationwide, population-based, retrospective cohort study to examine the association between the history of gout and risk of glaucoma by using the Longitudinal Health Insurance Database (LHID) of Taiwan. The gout cohort included 52 943 patients with newly diagnosed gout who were recruited between 2000 and 2012. Each patient was propensity score matching with 1:1 person without gout from the LHID. To determine glaucoma occurrence, the study population was followed up until the end of 2013. Cumulative incidence, hazard ratios (HRs), and 95% confidence intervals (CIs) were calculated after adjusting for age, sex, comorbidities, and ever ophthalmic visit. A Cox proportional hazard model was used to analyse the association between gout and incidence of glaucoma amongst patients with different potential risks. RESULTS: The adjusted HR for newly diagnosed glaucoma in the gout cohort was 1.00 (95% CI = 0.93-1.07, P = .931), compared with the non-gout cohort. Stratified subgroup analysis revealed that the HRs of glaucoma were 1.36 (95% CI = 1.09-1.70, P = .007), 0.99 (95% CI = 0.87-1.12, P = .871), and 0.95 (95% CI = 0.87-1.03, P = .235) in patients with gout aged 20-39, 40-54, and ≥55 years, respectively (P for interaction = .011). CONCLUSION: This nationwide population-based cohort study revealed that gout patients in the age group 20-39 years had a higher risk of glaucoma than non-gout controls.

Risk of non-typhoidal Salmonella infection in patients with cholecystectomy: Results from a nationwide matched cohort study in Taiwan.

BACKGROUND: The current study was designed to investigate the association between cholecystectomy and the risk of non-typhoidal Salmonella (NTS) infection. METHODS: We obtained claims-based data from the Taiwan National Health Insurance Research Database (NHIRD) to perform a nationwide cohort study. A propensity score (PS)-matching analysis was performed with a ratio of 1:2 in the cholecystectomy cohort and cholecystectomy-free group to reduce selection bias. Both groups were followed until NTS diagnosis, a dropout from the insurance programme or the end of 2013. Cox proportional hazard regression analysis was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for the risk of NTS infection between the cholecystectomy and cholecystectomy-free groups. RESULTS: Our study enrolled 197 444 patients who had undergone cholecystectomy and 394 888 patients who did not receive cholecystectomy. The adjusted HR (aHR) of NTS infection was 1.34 (95% CI, 1.13-1.58; P < .001) for the cholecystectomy group after adjusting for demographical characteristics and relevant comorbidities. The study population is predominantly female patients (55%) and older (58% older than 50 years). The subgroup analysis revealed that both sexes and notably, patients aged >50, who underwent cholecystectomy had a higher risk of NTS infection than the matched controls. Follow-up of patients who underwent cholecystectomy showed that they had a significantly higher risk of NTS infection for more than 6 months after the procedure. CONCLUSIONS: Our study showed that cholecystectomy might be an independent risk factor for subsequent NTS infection.

Incidence of dementia after dengue fever: Results of a longitudinal population-based study.

OBJECTIVE: To investigate the epidemiological relationship between dengue fever and the subsequent development of dementia. METHODS: Using nationwide Taiwan registries from the National Health Insurance Research (NHIRD), we identified adults aged over 40 years who received a dengue fever diagnosis from 1 January 2000 to 31 December 2012 and who did not have a history of dementia. We used a propensity score match (PSM) to balance the baseline characteristics between groups. All eligible adults were sorted into either the dengue group or non-dengue group at a ratio of 1:4, matching by age, sex, index years, income level, and relevant comorbidities. Using Cox regression with proportional hazards models, we estimated the risk of dementia. The study period started from 1 January 2000 to 31 December 2013. We conducted sensitivity analyses to cross-validate study results. RESULTS: With a median of 8.01 years of follow-up, patients in the dengue group were more at risk of developing dementia than the non-dengue group. The estimated cumulative incidence of dementia was 7.21% in the dengue group and 4.03% in the non-dengue group (adjusted hazard ratio (aHR), 1.71; 95% CI, 1.03 to 2.83). Sensitivity analyses yielded consistent findings. We excluded any stroke cases before the end of the study, and subgroup analysis by follow-up time showed that the dengue group has a significantly higher risk of new-onset dementia >6 years after the index date (aHR 3.24; 95% CI, 1.42 to 7.37). The P value for interaction was significant (<.0001). CONCLUSIONS: This study demonstrated a significantly higher risk of dementia in patients with dengue fever in Taiwan than in those without dengue fever.

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.

Flat foot and spinal degeneration: Evidence from nationwide population-based cohort study.

BACKGROUND/PURPOSE: Flat foot can alter the lower limb alignment and cause knee and back pain. To explore the association between flat foot and spinal degeneration. METHODS: By using a claims dataset containing 1 million random samples, individuals with flat foot were identified between January 1, 2000, and December 31, 2013. The study assembled a flat foot group and a matched non-flat foot group. Definition of flat foot was according to International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. The diagnosis date was defined as the index date for follow-up initiation. The follow-up period was defined as the duration from the index date (or nested index date for controls) to the occurrence of spinal degenerative joint disease (DJD), or December 31, 2013. The primary outcome was record of spinal DJD retrieved from the same database. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), with the control group as a reference. RESULTS: We identified 13,965 patients (most aged <30 years, 88%); 2793 patients were assigned to the flat foot group and 11,172 individuals to the non-flat foot group matched by age, sex, and index year. The mean follow-up duration was approximately 74 months. In total, 329 (11.78%) patients in the study group and 931 (8.33%) patients in the comparison group developed spinal DJD. The adjusted HR (95% CI) of spinal DJD for study group was 1.423(1.250-1.619) compared with the control. Sensitivity analyses with propensity score match and different scenario about spinal DJD enrollment showed similar results. Subgroup analysis showed that in patients aged >45 years with history of flat foot, the adjusted hazard ratios were 1.434, 3.065, 3.110, and 2.061 in association with spondylosis, intervertebral disc disorder, cervical stenosis, thoracic-lumbar-sacral stenosis, respectively. CONCLUSION: Flat foot was found to be an independent risk factor for subsequent spinal DJD.

An Improved Proxy Re-Encryption Scheme for IoT-Based Data Outsourcing Services in Clouds.

IoT-based data outsourcing services in clouds could be regarded as a new trend in recent years, as they could reduce the hardware and software cost for enterprises and obtain higher flexibility. To securely transfer an encrypted message in the cloud, a so-called proxy re-encryption scheme is a better alternative. In such schemes, a ciphertext designated for a data aggregation is able to be re-encrypted as one designated for another by a semi-trusted proxy without decryption. In this paper, we introduce a secure proxy re-encryption protocol for IoT-based data outsourcing services in clouds. The proposed scheme is provably secure assuming the hardness of the bilinear inverse Diffie-Hellman problem (BIDHP). In particular, our scheme is bidirectional and supports the functionality of multi-hop, which allows an uploaded ciphertext to be transformed into a different one multiple times. The ciphertext length of our method is independent of the number of involved IoT nodes. Specifically, the re-encryption process only takes one exponentiation computation which is around 54 ms when sharing the data with 100 IoT devices. For each IoT node, the decryption process only requires two exponentiation computations. When compared with a related protocol presented by Kim and Lee, the proposed one also exhibits lower computational costs.

Association of Scrub Typhus With the Risk of Autoimmune Diseases: A Population-Based Cohort Study.

Infection plays a major role in the development of autoimmune diseases. In this study, we investigated the relationship between scrub typhus and systemic autoimmune diseases. We enrolled 6,928 hospitalized patients with scrub typhus between 2000 and 2012 from the Taiwan National Health Insurance Research Database, and we compared them with 27,712 selected inpatients who had never been diagnosed with scrub typhus (1:4 ratio, matched by age, sex, and index year) in relation to the risk of developing autoimmune diseases. Cox proportional hazards regression analysis was used to analyze the risk of autoimmune diseases by sex, age, and comorbidities, with hazard ratios and 95% confidence intervals. The adjusted hazard ratio for autoimmune diseases for the scrub typhus group was 2.4 (95% confidence interval: 1.66, 3.48, P < 0.0001) compared with the control group. Subgroup analysis showed that women aged <40 years had a significant higher risk of autoimmune diseases. The risk was significantly higher within 3 years after scrub typhus infection. In conclusion, a higher risk of autoimmune diseases was found among the scrub typhus group, especially for female patients, those aged <40 years, and within the first 3 years after getting scrub typhus.

Hydroxychloroquine may be associated with reduced risk of coronary artery diseases in patients with rheumatoid arthritis: A nationwide population-based cohort study.

OBJECTIVES: The aim of this study was to determine whether hydroxychloroquine (HCQ) usage is associated with incidental risk of coronary artery diseases (CAD) in patients with rheumatoid arthritis (RA). METHODS: The Longitudinal Health Insurance Database in Taiwan was used. The study cohort comprised of 1104 newly diagnosed RA patients between 2001-2010, and patients were followed until 31 December 2011. Patients with history of CAD before RA diagnosis were excluded. We define as HCQ users if the usage duration of HCQ>180 days and non-users if less than 90 days. After propensity score matching of age, sex, index date and comorbidities, the study cohort was comprised of 346 patients: 173 HCQ users and 173 non-users. The study outcome was incidence of CAD. Cox regression model was used to estimate the hazard ratio (HR) of disease after controlling for demographic, other comorbidities and drugs. We also evaluate the effects of HCQ use and CAD events on different characteristics of RA patients. RESULTS: Kaplan-Meier curves comparing the HCQ users and non-users revealed a statistical significant difference (P value of log-rank test <.001). The adjusted HR for HCQ users versus non-users for CAD events was 0.32 (95% CI, 0.18-0.56, P value <.01) over up to 10 years of follow-up. The adjusted HR (95% CI) of CAD for different age group, gender and other subgroups showed no effect of interaction among each subgroup analysis parameter. CONCLUSIONS: This study revealed association of decreased CAD risk in RA patients taking HCQ. The protective effect of HCQ on CAD is consistent regarding subgroup analysis on age, gender and different comorbidities groups.