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.

Onset of oral lichen planus following dental treatments: A nested case-control study.

INTRODUCTION: The exposure to amalgam restorations has been reported to bring about altered immunity followed by inflammation and infection. AIMS: This study aimed at identifying whether patients who received restorative or endodontic treatments, or tooth extraction, would have altered odds of developing oral lichen planus (OLP). MATERIAL AND METHODS: In this population-based nested case-control study, 421 cases of OLP and 1,684 controls were included after propensity score matching. Logistic regression was used to estimate the adjusted odds ratio (aOR) of OLP in individuals who had received amalgam and composite resin restorations, root canal therapy, and tooth extraction over a follow-up duration of five years. RESULTS: There were no significantly different odds of OLP for those who underwent either amalgam (aOR = 0.948, 95% CI = 0.853-1.053, p = 0.3170) or resin restorations (aOR = 1.007, 95% CI = 0.978-1.037, p = 0.6557) in both anterior and posterior teeth in an observational period of five  years after restorations. Root canal therapy was associated with significantly lower odds of OLP, with each additional root canal therapy attenuating the risk of OLP at an aOR of 0.771 (95% CI = 0.680-0.874, p = 0.0001) for both anterior (aOR = 0.786, 95% CI = 0.626-0.986, p = 0.0372) and posterior teeth (aOR = 0.762, 95% CI = 0.650-0.893, p = 0.0008). Likewise, each tooth extraction reduced the risk of OLP, with an aOR of 0.846 (95% CI = 0.772-0.927, p = 0.0003), especially for anterior teeth (aOR = 0.733, 95% CI = 0.595-0.904, p = 0.0037). CONCLUSIONS: We reported no significant association between dental restorations and consequent OLP, and significantly lower odds of OLP following both root canal therapy and tooth extraction.

Migraine and subsequent head and neck cancer: A nationwide population-based cohort study.

OBJECTIVES: The association of migraine with the risk of certain cancer has been reported. The aim of this pilot study was to examine the associations between migraine and the onset of head and neck cancers (HNC). MATERIALS AND METHODS: A total of 1755 individuals were identified through a nationwide population-based cohort registry in Taiwan between 2000 and 2013. The primary end point variable was new-onset head and neck cancers in patients with migraine versus non-migraine controls. Cox proportional hazard regression was used to derive the risk of HNC. Subgroup analyses were performed to determine subpopulations at risk of migraine-associated HNC. Sub-outcome analyses were carried out to provide the subtypes of migraine-associated HNC. Propensity score matching was utilized to validate the findings. RESULTS: A total of four patients out of 351 patients with migraine and seven out of 1404 non-migraine controls developed HNC. The incidence of HNC was higher in patients with migraine than that in non-migraine controls (108.93 vs. 48.77 per 100,000 person-years) (adjusted hazard ratio, aHR = 2.908, 95% CI = 0.808-10.469; p = 0.102). The risk of HNC in patients with migraine with aura (aHR = 5.454, 95% CI = 0.948-26.875; p = 0.264) and without aura (aHR = 2.777, 95% CI = 0.755-8.473; p = 0.118) was revealed. The incidence of non-nasopharyngeal HNC secondary to migraine (112.79 per 100,000 person-years) was higher than that of nasopharyngeal cancer secondary to migraine (105.33 per 100,000 person-years). CONCLUSION: A higher incidence of HNC was observed in a small sample of patients with migraine, especially in those with migraine with aura. Migraine-associated HNC included non-nasopharyngeal HNC. Studies with a larger sample are needed to confirm the finding of the high risk of HNC in people with migraine.

Performance of the European Society of Cardiology 0/1-Hour, 0/2-Hour, and 0/3-Hour Algorithms for Rapid Triage of Acute Myocardial Infarction : An International Collaborative Meta-analysis.

BACKGROUND: The 2020 European Society of Cardiology (ESC) guidelines recommend using the 0/1-hour and 0/2-hour algorithms over the 0/3-hour algorithm as the first and second choices of high-sensitivity cardiac troponin (hs-cTn)-based strategies for triage of patients with suspected acute myocardial infarction (AMI). PURPOSE: To evaluate the diagnostic accuracies of the ESC 0/1-hour, 0/2-hour, and 0/3-hour algorithms. DATA SOURCES: PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus from 1 January 2011 to 31 December 2020. (PROSPERO: CRD42020216479). STUDY SELECTION: Prospective studies that evaluated the ESC 0/1-hour, 0/2-hour, or 0/3-hour algorithms in adult patients presenting with suspected AMI. DATA EXTRACTION: The primary outcome was index AMI. Twenty unique cohorts were identified. Primary data were obtained from investigators of 16 cohorts and aggregate data were extracted from 4 cohorts. Two independent authors assessed each study for methodological quality. DATA SYNTHESIS: A total of 32 studies (20 cohorts) with 30 066 patients were analyzed. The 0/1-hour algorithm had a pooled sensitivity of 99.1% (95% CI, 98.5% to 99.5%) and negative predictive value (NPV) of 99.8% (CI, 99.6% to 99.9%) for ruling out AMI. The 0/2-hour algorithm had a pooled sensitivity of 98.6% (CI, 97.2% to 99.3%) and NPV of 99.6% (CI, 99.4% to 99.8%). The 0/3-hour algorithm had a pooled sensitivity of 93.7% (CI, 87.4% to 97.0%) and NPV of 98.7% (CI, 97.7% to 99.3%). Sensitivity of the 0/3-hour algorithm was attenuated in studies that did not use clinical criteria (GRACE score <140 and pain-free) compared with studies that used clinical criteria (90.2% [CI, 82.9 to 94.6] vs. 98.4% [CI, 88.6 to 99.8]). All 3 algorithms had similar specificities and positive predictive values for ruling in AMI, but heterogeneity across studies was substantial. Diagnostic performance was similar across the hs-cTnT (Elecsys; Roche), hs-cTnI (Architect; Abbott), and hs-cTnI (Centaur/Atellica; Siemens) assays. LIMITATION: Diagnostic accuracy, inclusion and exclusion criteria, and cardiac troponin sampling time varied among studies. CONCLUSION: The ESC 0/1-hour and 0/2-hour algorithms have higher sensitivities and NPVs than the 0/3-hour algorithm for index AMI. PRIMARY FUNDING SOURCE: National Taiwan University Hospital.

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.

The incidence and risk of cardiovascular events associated with immune checkpoint inhibitors in Asian populations.

OBJECTIVES: Immune checkpoint inhibitors are associated with adverse cardiovascular events. However, there are no data characterizing cardiovascular events among Asians on immune checkpoint inhibitors. We aim to determine the incidence and risk of cardiac events associated with immune checkpoint inhibitors in an Asian population. METHODS: We performed a retrospective, propensity score-matched cohort study at two tertiary referral centers in Taiwan. Immune checkpoint inhibitor users were matched with non-immune checkpoint inhibitor users based on predetermined clinical variables. The primary outcome was major adverse cardiovascular events, defined as a composite of myocardial infarction, ischemic stroke, acute peripheral occlusive disease, pulmonary embolism, deep venous thrombosis, heart failure, pericardial disease, myocarditis, cardiac arrhythmias and conduction block. RESULTS: Between January 2010 and November 2021, 868 immune checkpoint inhibitor users were matched 1:1 with non-immune checkpoint inhibitor users. Among immune checkpoint inhibitor users, 67 (7.7%) patients developed major adverse cardiovascular events. During a median follow-up period of 188 days, the incidence rate of major adverse cardiovascular events for immune checkpoint inhibitor and non-immune checkpoint inhibitor users was 94.8 and 46.2 per 1000 patient-years, respectively, resulting in an incidence rate ratio of 2.1 [95% confidence interval: 1.5-2.9]. In multivariate Cox proportional hazard models, immune checkpoint inhibitor users had a 60% increased risk for major adverse cardiovascular events [hazard ratio, 1.6 (95% confidence interval: 1.1-2.3)]. Immune checkpoint inhibitors use was independently associated with increased risk of ischemic stroke [hazard ratio, 3.0 (95% confidence interval: 1.0-9.0)] and pulmonary embolism [hazard ratio, 5.5 (95% confidence interval: 1.4-21.3)]. In multivariate logistic regression analysis, age > 65, metastatic disease, hypertension and baseline platelet-to-lymphocyte ratio < 180 were risk factors for major adverse cardiovascular events. CONCLUSIONS: Among Asians, immune checkpoint inhibitors were associated with an increased risk of major adverse cardiovascular events, particularly ischemic stroke and pulmonary embolism.

Gender differences in health protective behaviours and its implications for COVID-19 pandemic in Taiwan: a population-based study.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection produces more severe symptoms and a higher mortality in men than in women. The role of biological sex in the immune response to SARS-CoV-2 is believed to explain this sex disparity. However, the contribution of gender factors that influence health protective behaviors and therefore health outcomes, remains poorly explored. METHODS: We assessed the contributions of gender in attitudes towards the COVID-19 pandemic, using a hypothetical influenza pandemic data from the 2019 Taiwan Social Change Survey. Participants were selected through a stratified, three-stage probability proportional-to-size sampling from across the nation, to fill in questionnaires that asked about their perception of the hypothetical pandemic, and intention to adopt health protective behaviors. RESULTS: A total of 1,990 participants (median age = 45·92 years, 49% were women) were included. Significant gender disparities (p < .001) were observed. The risk perception of pandemic (OR = 1·28, 95% CI [1·21 - 1·35], p < .001), older age (OR = 1·06, 95% CI [1·05 - 1·07], p < .001), female gender (OR = 1·18, 95% CI [1·09-1·27], p < .001), higher education (OR = 1·10, 95% CI [1·06 - 1·13], p < .001), and larger family size (OR = 1·09, 95% CI [1·06 - 1·15], p < .001) were positively associated with health protective behaviors. The risk perception of pandemic (OR = 1·25, 95% CI [1·15 - 1·36]), higher education (OR = 1·07, 95% CI [1·02 - 1·13], p < .05), being married (OR = 1·17, 95% CI [1·01-1·36, p < .05), and larger family size (OR = 1·33, 95% CI [1·25 - 1·42], p < .001), were positively associated with intention to receive a vaccine. However, female gender was negatively associated with intention to receive a vaccine (OR = 0·85, 95% CI [0·75 - 0·90], p < ·01) and to comply with contact-tracing (OR = 0·95, 95% CI [0·90 - 1·00], p < .05) compared to men. Living with children was also negatively associated with intention to receive vaccines (OR = 0·77, 95% CI [0·66 - 0·90], p < .001). CONCLUSION: This study unveils gender differences in risk perception, health protective behaviors, vaccine hesitancy, and compliance with contact-tracing using a hypothetical viral pandemic. Gender-specific health education raising awareness of health protective behaviors may be beneficial to prevent future pandemics.

Severity of periodontitis and salivary interleukin-1ß are associated with psoriasis involvement.

BACKGROUND/PURPOSE: Both psoriasis and periodontal diseases are characterized by an exaggerated immune response to the microbiota residing on epithelial surfaces. This study aimed to explore the associations between the severity of psoriasis and periodontal destruction in patients with psoriasis. METHODS: Thirty-three patients diagnosed with psoriasis were referred from the dermatology clinic of National Taiwan University Hospital. Full-mouth periodontal examination was performed and saliva was collected after patients signed informed consent forms. The Psoriasis Area Severity Index (PASI) as well as clinical periodontal parameters including probing depth (PD), plaque index (PI), gingival index (GI), and clinical attachment level (CAL) were evaluated. Salivary cytokines including interleukin (IL)-1ß, IL-12, IL-17, interferon-γ, and tumor necrosis factor (TNF)-α were tested with the Luminex Bio-Plex system. Anti-inflammatory medication, tobacco use, and underlying comorbidities were included in the analysis. RESULTS: Baseline PASI was significantly associated with PI. PASI at follow-up was positively correlated with CAL ≥ 4 mm (%) and saliva IL-1ß levels. Psoriasis patients who used non-steroidal anti-inflammatory drugs or topical steroids had significantly lower GI, PD ≥ 4 mm (%), and saliva IL-1ß and TNF-α levels. Moreover, a history of tobacco use was associated with higher PD ≥ 4 mm (%). CONCLUSION: PI, CAL, and salivary IL-1ß were associated with PASI. Periodontal severity was associated with psoriasis involvement. Periodontal inflammation in psoriasis may be modified by anti-inflammatory medication and tobacco use. Additional large-scale longitudinal and mechanistic studies are needed.

Patients with juvenile idiopathic arthritis are at increased risk for obstructive sleep apnoea: a population-based cohort study.

BACKGROUND AND OBJECTIVES: Juvenile idiopathic arthritis (JIA), an autoimmune disease, has been proposed to be comorbid with obstructive sleep apnoea (OSA). We aimed at testing the hypothesis that patients with JIA may presented with high risk of OSA in a cohort study. SUBJECTS AND METHODS: This is a cohort study including patients with JIA from 1999 to 2013 identified from a longitudinal health registry. A matched non-JIA control group was also included. The primary outcome variable was presence of OSA. A Cox proportional hazard model was developed to estimate the risk of OSA in patients with JIA. A cumulative probability model was adopted to assess the time-dependent effect of JIA on OSA development, implying a causal link of the association. RESULTS: A total of 2791 patients with JIA were included, and 11 164 individuals without JIA were selected as matched controls. A total of 95 included subjects had OSA: 31 in the JIA group and 64 in the control group. Patients with JIA were more likely to have OSA compared with controls (adjusted hazard ratio, aHR = 1.922, 95% confidence interval [CI] = 1.244-2.970). The incidence of developing OSA was particularly high among patients with JIA-associated deformity that presented at age 18-30 years (aHR = 1.993, 95% CI = 1.277-3.113) and males (aHR = 1.786, 95% CI = 1.097-2.906). The risk of developing OSA increased over 60 months (aHR = 2.523, 95% CI = 1.322-4.815) of follow-up after the JIA diagnosis. CONCLUSIONS: Patients with JIA have a significantly increased risk of developing OSA compared with matched individuals without JIA.

Teaching evidence-based medicine with electronic databases for preclinical education.

To evaluate the efficacy of an educational module on evidence-based medicine (EBM) assisted with electronic medical databases (EMDs) for preclinical education, medical students (n = 111) were matriculated in a program consisted of 16 2-h sessions on EBM plus hands-on experience on EMDs in a problem-based learning-type format. Students were required to make an oral presentation on designated clinical scenarios before and after the sessions, without prior notice, as an indicator of performance. In addition, questionnaires focusing on behavioral changes, awareness, and confidence of mastering EBM were administered before and after the sessions to assess the attitudinal and behavioral impact of the intervention on the participants. We found evidence of better postprogram performance in utilizing EBM-relevant concepts and resources when the enrolled medical students were giving oral presentations. Moreover, the participants reported increased awareness of EBM and, behaviorally, increased utilization of EBM-relevant resources provided by libraries. Also, they reported improvement on appropriately using EBM-relevant resources, and 99% of the participants reported strong confidence in practicing EBM. In conclusion, modules on EBM implemented with EMDs benefitted medical students in scenario-oriented PBL tutorials. Improvements in awareness, behavior, confidence, and performance in mastering EBM were noted.

New-onset keratitis associated with epidermal growth factor receptor-based targeted therapies in Han Chinese patients with lung cancer: A multi-center cohort study.

PURPOSE: To determine the risk and incidence of keratitis following treatment with epidermal growth factor receptor inhibitors (EGFRi) and subtypes of EGFRi-associated keratitis. METHODS: This multi-center cohort study included EGFRi-treated patients and non-users with lung cancer between 2010 and 2023. EGFRi included first-generation agent gefitinib and erlotinib, second-generation agent afatinib, and third-generation agent osimertinib. The primary outcome was new-onset keratitis. Cox proportional hazard models with multivariable adjustment were applied to determine the effect of EGFRi on keratitis over time. Subgroup analyses were conducted, stratified by agents of EGFRi. Sub-outcome analyses were performed to identify the subtypes of EGFRi-associated keratitis. RESULTS: A total of 1549 EGFRi-treated patients and 6146 non-users were included. 38 (2.5%) EGFRi-treated patients developed keratitis. The incidence of keratitis in EGFRi-treated patients was significantly higher than that in controls (incidence rate, IR, per 1000 person-years = 14.7 vs 4.49, p < 0.0001). EGFRi-treated patients presented with an increased risk for keratitis (adjusted hazard ratio, aHR = 3.14, 95% CI = 1.85-5.35, p < 0.001). Erlotinib (aHR = 2.64, 95% CI = 1.35-5.15, p = 0.004), afatinib (aHR = 4.42, 95% CI = 2.17-9.02, p < 0.001), and osimertinib (aHR = 4.67, 95% CI = 1.60-13.64, p = 0.005), but not gefitinib (aHR = 2.30, 95% CI = 0.96-5.55, p = 0.063), significantly contributed to the risk of keratitis. Subtypes of EGFRi-associated keratitis included corneal ulcer (IR = 2.31 vs 0.166, p < 0.0001) and keratoconjunctivitis (IR = 9.27 vs 2.91, p < 0.0001). None of the EGFRi-treated patients developed perforated corneal ulcer, interstitial and deep keratitis, or corneal neovascularization. CONCLUSION: Treatment with EGFRi was associated with an increased risk of keratitis. Ocular toxicity of EGFRi was highest for third-generation agents, followed by second-generation agents, and then first-generation agents.

Epidermal Growth Factor Receptor Inhibitors for Lung Cancer and the Risk of Keratitis.

Importance: Epidermal growth factor receptor inhibitors (EGFRis) have been reported to be associated with cutaneous and ocular side effects; however, there is limited evidence of an association between EGFRi treatment and keratitis. Objective: To determine the association between EGFRi treatment and agents and the risk of new-onset keratitis among patients with lung cancer. Design, Setting, and Participants: This US population-based cohort study examined TriNetX data of patients with lung cancer treated with or without EGFRis between May 1, 2003, and October 30, 2023. Exposures: Treatment with EGFRis, including the first-generation agents gefitinib and erlotinib, the second-generation agent afatinib, and the third-generation agent osimertinib. Main Outcomes and Measures: The risk of new-onset keratitis among patients with lung cancer receiving EGFRi treatment was determined using logistic and Cox proportional hazards regression. Results: Among 1 388 108 patients with lung cancer, 22 225 received EGFRis (mean [SD] age, 69.7 [10.6] years; 62.8% females and 37.2% males). Patients treated with EGFRis had a higher risk of keratitis than nonexposed patients (hazard ratio [HR], 1.520; 95% CI, 1.339-1.725). Subtypes of EGFRi-associated keratitis included keratoconjunctivitis (HR, 1.367; 95% CI, 1.158-1.615), superficial keratitis (HR, 1.635; 95% CI, 1.306-2.047), and corneal ulcer (HR, 2.132; 95% CI, 1.515-3.002). Patients taking afatinib had a higher risk of keratitis (HR, 2.229; 95% CI, 1.480-3.356). Conclusions and Relevance: These findings suggest that patients with lung cancer treated with EGFRis may have an increased risk of new-onset keratitis, especially with the second-generation EGFRi afatinib, supporting the need for prompt diagnosis and management of EGFRi-associated ocular issues to prevent serious complications or treatment disruptions.