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In a country with a high prevalence of cigarette smoking, betel chewing, and alcohol drinking, cancers of the oral cavity, nasopharynx, and larynx were the fourth, twelfth and seventeenth leading causes of cancer death, respectively, for men in 2020. We analyzed patients with head and neck cancer from 1980 to 2019 from the Taiwan Cancer Registration Database and discussed the annual average percent change, average percent change, age period, and birth cohort. Obvious period effects and birth effects are seen in oral, oropharyngeal, and hypopharyngeal cancer; however, the most significant period effect was seen between 1990 and 2009, which mainly reflects the consumption of betel nuts per capita. In addition, the period effect lessens after 2010 in oral cancer and hypopharyngeal cancers, while oropharyngeal cancers remain an obvious period effect, which results from the rising prevalence of HPV. Due to the high prevalence rate of betel quid chewing and cigarette smoking in the 1990s, the government executed several acts. As a result, the age-adjusted incidence rates of oral, oropharyngeal, and hypopharyngeal cancers have flattened since 2010, which can be explained by the declining cigarette smoking rate. The strict policy indeed shows an obvious effect on the head and neck cancer incidence rates, and we expect to see a further decline in the future.

Background Manual dexterity is key to clinical skill training. The networking between sensorimotor and visual-attention functions may be associated with the expertise of dental students. The study aims to investigate the pattern of networking between sensorimotor and visual-attention functions and related resting-state (rs) functional connectivity (FC). Methods Twenty-six dental and 19 non-dental students completed visual-attention tests and psychomotor tests for manual dexterity and steadiness. Thirty participants also received structural and rs-functional magnetic resonance imaging. Results Compared to non-dental students, dental students showed increased networking in performance between visual-attention tests and manual dexterity, increased rsFC between bilateral sensorimotor network (SMN) and the left middle frontal gyrus, and decreased rsFC between bilateral SMN and the left posterior insula. Better performance of manual dexterity was associated with increased rsFC between the left SMN and the right supramarginal gyrus. Conclusions Dental skill training is associated with the networking of sensorimotor and visual-attention functions and coupled with increased rsFC of the SMN. In dental students, better manual dexterity is associated with the functional connectivity of the SMN. Clinical trial number Not applicable.

Background The use of fixed combination antiretroviral therapy with a low genetic barrier for the treatment of patients infected with human immunodeficiency virus (HIV) may affect the local HIV transmitted drug resistance (TDR) pattern. The present study aimed to investigate changes in the prevalence of HIV TDR following the implementation of a fixed regimen of HIV treatment in Taiwan in 2012. Methods TDR was measured in antiretroviral treatment-naïve HIV-1-infected individuals who participated in voluntary counseling and testing between 2007 and 2015 in southern Taiwan. Antiretroviral resistance mutations were interpreted using the HIVdb program from the Stanford University HIV Drug Resistance Database. Results Sequences were obtained from 377 consecutive individuals between 2007 and 2015. The overall prevalence rates of TDR HIV among the study population from 2007 to 2011 and 2012–2015 were 10.6 and 7.9%, respectively. Among the detected mutations, K103 N and V179D + K103R were more frequently observed after 2012. Four HIV-infected patients with K103 N variants were detected after 2012, and 4 of the 5 patients with V179D + K103R variants were found after 2012. No significant differences were observed in the TDRs among nucleoside reverse transcriptase inhibitors (NRTIs), non-NRTIs (NNRTIs), protease inhibitors, multiple drug resistance, and any drug resistance between period 1 (2007–2011) and period 2 (2012–2015). Conclusions A fixed treatment regimen with zidovudine/lamivudine + efavirenz or nevirapine as first-line therapy for treatment-naïve patients infected with HIV did not significantly increase the TDR during the 4-year follow-up period. Due to the increase in NNRTI resistance associated with mutations after 2012, a longer follow-up period and larger sample size are needed in future studies.

Background: The prevalence of transmitted drug resistance (TDR) after the universal implementation of STRs is unknown in Taiwan. Objective: This study aimed to investigate the prevalence of TDR in patients with HIV-1 infection, clarify the risk factors for pol resistance, and compare differences in HIV drug resistance before and after the implementation of STRs in Taiwan. Methods: Adult patients infected with HIV-1 were enrolled in this study from 2013 to 2021. Mutations associated with drug resistance were identified using the 2019 International Antiviral Society-USA list of drug resistant mutations in HIV, and drug susceptibility was assessed according to the Stanford HIV Drug Resistance Database edition 9. A logistic regression model was used to analyze the risk factors for pol resistance, and the differences in the prevalence of drug resistance from 2013-2016 to 2017-2021 were compared using the Mann-Whitney H-test. General linear regression was used to analyze temporal changes in the annual proportion of TDR overall and by type of antiretroviral drugs. Results: A total of 369 patients were included. The prevalence rate of pol resistance was 9.8% (36/369). The resistance rates to nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and integrase strand transfer inhibitors (INSTIs) were 3.3%, 6.9%, 0% and 1.8%, respectively. The patients with hepatitis C infection were more likely to have pol resistance (aHR 5.767, CI 1.232-26.991, p=0.026). The prevalence rate of pol resistance did not decrease after the implementation of STRs as first-line therapy in 2017 (11.2% vs 8.7%, aHR 1.329, CI 0.667-2.645, p=0.480), and no significant temporal changes were shown in the annual proportion of TDR overall or by type of antiretroviral drug. Conclusion: Our findings showed a stable prevalence rate of transmitted drug resistance despite the implementation of STRs as the first-line therapy in June 2016. Keywords: HIV, transmitted drug resistance, single-tablet regimen

Background Epidemiological studies have reported the association between hypertension and exposure to road traffic noise, but the association between noise frequency characteristics is not clear. This study investigated the association between exposure to different frequency components of road traffic noise and the prevalence of hypertension in central Taiwan. Methods We recruited 820 residents living near main roads for more than 3 years. Frequency components of traffic noise and traffic flow rates during 0900–1700 on weekdays were measured simultaneously in 2008. Multiple logistic regressions were conducted to estimate odds ratios (ORs) for diagnosed hypertension, adjusting for potential confounders and the total traffic flow rate. Results The high-exposure group (≥ the median of noise levels [decibels, dB]) at 63 Hz, 125 Hz and 1000 Hz had ORs for hypertension of 2.77 (95% confidence interval [CI]: 1.17-6.52), 4.08 (95% CI: 1.57-10.63) and 1.98 (1.00-3.92) (95% CI: 1.00-3.92), respectively, compared to the low-exposure group (< the median of noise levels [dB]). There was an increasing trend in the prevalence of hypertension by exposure to road traffic noise at 63, 125 and 1000 Hz in all subjects and in men. Total subjects exposed to ≥ 51 dB at 125 Hz had an OR of 4.65 (95% CI = 1.46-14.83) compared to those exposed to < 47 dB. Conclusions With the possible bias of exposure misclassification and a bias from using diagnosed hypertension, these results suggest that exposure to road traffic noise at low and hearing-sensitive frequencies may be associated with hypertension and exposure to noise at 125 Hz may have the greatest risk for hypertension.

•Taiwan launched government-funded HPV vaccination in 2008 and extended it to nationwide vaccination for 7th grade girls in 2018.•Serious AE were evaluated by comparing the vaccinated group with same age groups girls using a Standardized Incidence Ratio.•The results using Asian populations suggest that the HPV vaccine has a limited number of significant adverse effects. The safety of human papillomavirus (HPV) vaccines has been evaluated continuously in pre-licensure clinical trials, post-marketing surveillance systems, and observational studies. Most studies have found no significant association between serious adverse events and HPV vaccination. However, these studies have focused on Western populations; similar studies focusing on Asian populations are insufficient. Our retrospective cohort study used the HPV-vaccination records of junior high-school adolescent girls aged 12–15 years between 2013 and 2018 in Taiwan’s National Immunization Information System and linked them to a registry for beneficiaries in Taiwan’s National Health Insurance Database (NHID) to establish the vaccinated group. We selected 19 serious diseases as serious adverse events. We compared the incidence rates of these serious adverse events between the vaccinated group and girls in the same age group population, and we calculated the standardized incidence ratio (SIR) to evaluate the risk of serious adverse events after HPV vaccination. Because of the onset of different types of diseases, we set three periods after the subjects received HPV vaccination: within 3 months, within 1 year, and during the study period (2013–2018). The results showed the incidence rates and the SIRs of 19 selected adverse events. Among the 19 selected serious adverse events, the disease with the highest incidence rate during the study period was fibromyalgia (73.23 cases per million population), and the disease with the lowest incidence rate during the study period was Crohn’s disease (0.15 cases per million population). The results showed no statistically significant increases in the risk of 19 selected serious adverse events and indicated no association between HPV vaccination and serious adverse events. Given the benefits and safety of HPV vaccination, our research can reduce concerns about vaccine side effects, inform health policies and improve public and clinician’s acceptance of HPV vaccine policy.

The association between human leukocyte antigen (HLA) genes (located in the Major Histocompatibility Complex [MHC] region of chromosome 6p21) and NPC has been known for some time. Recently, two genome-wide association studies (GWAS) conducted in Taiwan and China confirmed that the strongest evidence for NPC association was mapped to the MHC region. It is still unclear, however, whether these findings reflect direct associations with Human Leukocyte Antigen (HLA) genes and/or to other genes in this gene-rich region. To better understand genetic associations for NPC within the MHC region of chromosome 6, we conducted an evaluation that pooled two previously conducted NPC case-control studies in Taiwan (N = 591 cases and N = 521 controls). PCR-based genotyping was performed for 12 significant SNPs identified within 6p21 in the Taiwan NPC GWAS and for the HLA-A gene (exons 2 and 3). After confirming homogeneity between the two studies, pooled odds ratios (OR) and 95% confidence intervals (CI) were estimated by logistic regression. We found that HLA-A (p-trend = 0.0006) and rs29232 (within the GABBR1 gene; p-trend = 0.005) were independent risk factors for NPC after adjustment for age, gender, study and each other. NPC risk was highest among individuals who were homozygous for the HLA-A*0207 risk allele and carriers of the rs29232 risk allele (A). Our study suggests that most of the SNPs significantly associated with NPC from GWAS reflect previously identified HLA-A associations. An independent effect of rs29232 (GABBR1), however, remained, suggesting that additional genes within this region might be associated with NPC risk.

Integrase strand transfer inhibitors (INSTIs) are used as first-line therapy for HIV-1-infected patients. Next-generation sequencing (NGS) can detect low-frequency mutants; however, the clinical value of NGS to detect resistance variants is unknown. This study aimed to evaluate the prevalence of INSTI resistance in southern Taiwan and determine the clinical implications of using NGS to detect integrase region low-level resistant variants. This retrospective cohort study included antiretroviral therapy-naïve HIV-1-infected individuals at Kaohsiung Veterans General Hospital, Taiwan, from 2013 to 2017. Drug-resistance mutations were determined, and an in-house polymerase chain reaction was used for genotyping INSTI resistance. NGS was used to assess INSTI resistance (≧1%), and the results were compared with those from population sequencing. Drug resistance-associated mutations were defined according to the 2019 IAS-USA HIV drug resistance-associated mutations list, and accessory mutations by a Stanford HIVdb score ≥10 to at least one INSTI. A total of 224 patients were included. Subtype B HIV-1 strains were found in 96% of the individuals and subtype CRF01_AE in 4%. The prevalence rates for nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors and INSTI resistance were 4%, 5.8%, 0.4% and 0.9%, respectively. The most common INSTI resistance-associated mutations were G163K (0.4%) and E138A (0.4%). Of the 38 patients diagnosed in 2017 who had both NGS and population sequencing data, none had INSTI resistance-associated mutations by population sequencing; however, NGS detected four more INSTI resistance-associated mutations with low frequencies (G163R 3.25%, S153F 3.21%, S153Y 1.36% and Y143H 2.06%). Two patients with S153F and S153Y low frequencies mutations started INSTI-based highly active antiretroviral therapy, and none had virological failure by week 48. Our findings showed a low rate of HIV drug resistance to INSTIs (0.9%) in treatment-naïve patients. NGS detected more INSTI resistance-associated mutations at a low frequency. Low-level drug resistance-associated mutations to INSTIs identified by NGS did not have an impact on the treatment response to INSTI-based first-line therapy.

INTRODUCTION:The prospective study aimed to investigate the long-term associated risks of cirrhosis and hepatocellular carcinoma (HCC) across various subtypes of steatotic liver disease (SLD).METHODS:We enrolled 332,175 adults who participated in a health screening program between 1997 and 2013. Participants were categorized into various subtypes, including metabolic dysfunction-associated SLD (MASLD), MASLD with excessive alcohol consumption (MetALD), and alcohol-related liver disease (ALD), based on ultrasonography findings, alcohol consumption patterns, and cardiometabolic risk factors. We used computerized data linkage with nationwide registries from 1997 to 2019 to ascertain the incidence of cirrhosis and HCC.RESULTS:After a median follow-up of 16 years, 4,458 cases of cirrhosis and 1,392 cases of HCC occurred in the entire cohort, resulting in an incidence rate of 86.1 and 26.8 per 100,000 person-years, respectively. The ALD group exhibited the highest incidence rate for cirrhosis and HCC, followed by MetALD, MASLD, and non-SLD groups. The multivariate adjusted hazard ratios for HCC were 1.92 (95% confidence interval [CI] 1.51-2.44), 2.91 (95% CI 2.11-4.03), and 2.59 (95% CI 1.93-3.48) for MASLD, MetALD, and ALD, respectively, when compared with non-SLD without cardiometabolic risk factors. The pattern of the associated risk of cirrhosis was similar to that of HCC (all P value <0.001). The associated risk of cirrhosis for ALD increased to 4.74 (95% CI 4.08-5.52) when using non-SLD without cardiometabolic risk factors as a reference.DISCUSSION:This study highlights elevated risks of cirrhosis and HCC across various subtypes of SLD compared with non-SLD, emphasizing the importance of behavioral modifications for early prevention.

Drug resistance to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs) has been associated with loss of viral suppression measured by a rise in HIV-1 RNA levels, a decline in CD4 cell counts, persistence on a failing treatment regimen, and lack of adherence to combination antiretroviral therapy. This study aimed to monitor the prevalence and risk factors associated with drug resistance in Taiwan after failure of first-line therapy. Data from the Veterans General Hospital Surveillance and Monitor Network for the period 2009-2014 were analyzed. Plasma samples from patients diagnosed with virologic failure and an HIV-1 RNA viral load >1000 copies/mL were analyzed by the ViroSeq HIV-1 genotyping system for drug susceptibility. Hazard ratios (HRs) for drug resistance were calculated using a Cox proportional hazard model. From 2009 to 2014, 359 patients were tested for resistance. The median CD4 count and viral load (log) were 214 cells/μL (interquartile range [IQR]: 71-367) and 4.5 (IQR: 3.9-5.0), respectively. Subtype B HIV-1 strains were found in 90% of individuals. The resistance rate to any of the three classes of antiretroviral drugs (NRTI, NNRTI, and PI) was 75.5%. The percentage of NRTI, NNRTI, and PI resistance was 58.6%, 61.4%, and 11.4%, respectively. The risk factors for any class of drug resistance included age ≤35 years (adjusted HR: 2.30, CI: 1.48-3.56; <0.0001), initial NNRTI-based antiretroviral regimens (adjusted HR: 1.70, CI: 1.10-2.63; =0.018), and current NNRTI-based antiretroviral regimens when treatment failure occurs (odds ratio: 4.04, CI: 2.47-6.59; <0.001). There was no association between HIV-1 subtype, viral load, and resistance. This study demonstrated a high level of resistance to NRTI and NNRTI in patients with virologic failure to first-line antiretroviral therapy despite routine viral load monitoring. Educating younger men who have sex with men to maintain good adherence is crucial, as PI use is associated with lower possibility of drug resistance.